ASH 2010: Payers' Perspectives

Studies presented at the 2010annual meeting of the AmericanSociety of Hematology suggest

that patients with multiple myeloma(MM), lymphoma, and chronic myel-ogenous leukemia (CML) may havenew treatment options in the futurethat offer outcomes superior to currenttherapies when used individually or incombination with current therapies.Some of the products described in thisarticle are supported by pivotal orphase 2b data, whereas others are onlyin early-phase testing and are includedbecause experts consider them so

promising, as was emphasized at themeeting.

Multiple MyelomaCurrent treatment for MM is very

effective but not curative. Two drugsin preliminary testing that have shownimpressive survival rates and attractedmuch attention at the meeting are elo-tuzumab and pomalidomide.

Elotuzumab, a humanized mono-clonal antibody directed against theCS1 antigen, combined with lenalido-mide and dexamethasone, achieved avery high response rate (81%) in the

Hematology Drug Pipeline Is RobustNovel Therapies with Promising Options By Caroline Helwick

©2011 Engage Healthcare Communications, LLC

AEuropean or Canadian ap -proach to making formularydecisions is the inevitable

future. In other words, costs must beweighed against benefits, according toJoseph Mikhael, MD, of the MayoClinic, AZ, a self-described “health-care economics wonk,” who spoke ata session at the 2010 American Societyof Hematology’s annual meeting onthe new pharmacoeconomics in can-cer care.

Dr Mikhael suggested that the audi-ence consider that “US medical insur-ance costs are rising faster than earn-ings and general inflation.”Bevacizumab, approved for lung

and colon cancers, costs $4000 to $9000per month. Cetuximab, which isapproved for colon and head and neckcancers, costs $17,000 per month.Many physicians are uncomfortablewith discussing drug price; they aresupposed to be their patients’ ultimate

Pharmacoeconomics:Hematologists Should Preparefor the Coming Debate on Costsversus BenefitsBy Neil Canavan

Continued on page 6

Continued on page 26

THE PEER-REVIEWED FORUM FOR EVIDENCE IN BENEFIT DESIGN™

February 2011 I Vol 4, No 1 I SPECIAL ISSUE

Healthcare ReformAddresses Quality of Carefor AmericansOncologist and Policy Expert Dispels Many Myths By Caroline Helwick

The richer the nation, the more itspends on healthcare, “but theUS is phenomenally off the

chart,” spending a total of $2.4 trillionannually, or $7300 per person in 2007.By contrast, the next biggest spendersare Switzerland and Norway, and

they spend 40% less, said Ezekiel J.Emanuel, MD, PhD, then-SpecialAdvisor for Health Policy in theOffice of Man agement and Budget,and Chair of the Department ofBioethics at the National Institutesof Health.

FOR PAYERS, PURCHASERS, POLICYMAKERS, AND OTHER HEALTHCARE STAKEHOLDERS

Ezekiel J. Emanuel,MD, PhD

ASH 2010: PAYERS’ PERSPECTIVESAMERICAN SOCIETY OF HEMATOLOGY HIGHLIGHTS

Hal E. Broxmeyer, PhD, Distinguished Professor of Microbiology and Immunology, IndianaUni versity School of Medicine, addressing attendees at the ASH 2010 Annual Meeting in Orlando.

Photo by Curtis Com

pton, courte

sy of the American Society of H

ematology.

Continued on page 7

HEALTH ECONOMICS . . . . . . . . . . .6Healthcare survival depends on innovationThrombotic microangiopathies total $227.4 million annuallyNew outpatient treatment criteria for PE can cut costs

NON-HODGKIN LYMPHOMA . .13Rituximab effective in several combinations and in asymptomatic patients

HODGKIN LYMPHOMA . . . . . . .15Brentuximab promising Rx for refractory disease

LEUKEMIA . . . . . . . . . . . . . . . . .16Imatinib enhances overall survival in ALLExcellent outcomes with nilotinibPonatinib makes a splash

MULTIPLE MYELOMA . . . . . . . . 19Bortezomib-based induction emerging as new standardPromising drugs in the pipeline

MYELODYSPLASTIC SYNDROMES . . . . . . . . . . . . . . . 25First population-based MDS drug comparison

OTHER HIGHLIGHTS . . . . . . . . 26Incorporating genomic research into personalized medicine

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INDICATIONS:

VELCADE® (bortezomib) for Injection is indicated for the treatment of patients with multiple myeloma.VELCADE® (bortezomib) for Injection is indicated for the treatment of patients with mantle cell lymphomawho have received at least 1 prior therapy.

CONTRAINDICATIONS:

VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol.

WARNINGS AND PRECAUTIONS:

VELCADE should be administered under the supervision of a physician experienced in the use ofantineoplastic therapy. Complete blood counts (CBC) should be monitored frequently during treatment withVELCADE.

Pregnancy Category D: Women of childbearing potential should avoid becoming pregnant while beingtreated with VELCADE. Bortezomib administered to rabbits during organogenesis at a dose approximately0.5 times the clinical dose of 1.3 mg/m2 based on body surface area caused post-implantation loss and adecreased number of live fetuses.

Peripheral Neuropathy: VELCADE treatment causes a peripheral neuropathy that is predominantly sensory.However, cases of severe sensory and motor peripheral neuropathy have been reported. Patients withpre-existing symptoms (numbness, pain or a burning feeling in the feet or hands) and/or signs of peripheralneuropathy may experience worsening peripheral neuropathy (including ≥Grade 3) during treatment withVELCADE. Patients should be monitored for symptoms of neuropathy, such as a burning sensation,hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain or weakness. Patients experiencingnew or worsening peripheral neuropathy may require change in the dose and schedule of VELCADE.Following dose adjustments, improvement in or resolution of peripheral neuropathy was reported in 51%of patients with ≥Grade 2 peripheral neuropathy in the relapsed multiple myeloma study. Improvement inor resolution of peripheral neuropathy was reported in 73% of patients who discontinued due to Grade 2neuropathy or who had ≥Grade 3 peripheral neuropathy in the phase 2 multiple myeloma studies. Thelong-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma.

Hypotension: The incidence of hypotension (postural, orthostatic, and hypotension NOS) was 13%. Theseevents are observed throughout therapy. Caution should be used when treating patients with a history ofsyncope, patients receiving medications known to be associated with hypotension, and patients who aredehydrated. Management of orthostatic/postural hypotension may include adjustment of antihypertensivemedications, hydration, and administration of mineralocorticoids and/or sympathomimetics.

Cardiac Disorders: Acute development or exacerbation of congestive heart failure and new onset ofdecreased left ventricular ejection fraction have been reported, including reports in patients with no riskfactors for decreased left ventricular ejection fraction. Patients with risk factors for, or existing heart diseaseshould be closely monitored. In the relapsed multiple myeloma study, the incidence of any treatment-emergent cardiac disorder was 15% and 13% in the VELCADE and dexamethasone groups, respectively.The incidence of heart failure events (acute pulmonary edema, cardiac failure, congestive cardiac failure,cardiogenic shock, pulmonary edema) was similar in the VELCADE and dexamethasone groups, 5% and4%, respectively. There have been isolated cases of QT-interval prolongation in clinical studies; causalityhas not been established.

Pulmonary Disorders: There have been reports of acute diffuse infiltrative pulmonary disease of unknownetiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory DistressSyndrome (ARDS) in patients receiving VELCADE. Some of these events have been fatal. In a clinical trial,the first two patients given high-dose cytarabine (2 g/m2 per day) by continuous infusion with daunorubicinand VELCADE for relapsed acute myelogenous leukemia died of ARDS early in the course of therapy. Therehave been reports of pulmonary hypertension associated with VELCADE administration in the absence ofleft heart failure or significant pulmonary disease. In the event of new or worsening cardiopulmonarysymptoms, a prompt comprehensive diagnostic evaluation should be conducted.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): There have been reports of RPLS in patientsreceiving VELCADE. RPLS is a rare, reversible, neurological disorder which can present with seizure,hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances.Brain imaging, preferably MRI (Magnetic Resonance Imaging), is used to confirm the diagnosis. In patientsdeveloping RPLS, discontinue VELCADE. The safety of reinitiating VELCADE therapy in patients previouslyexperiencing RPLS is not known.

Gastrointestinal Adverse Events: VELCADE treatment can cause nausea, diarrhea, constipation, andvomiting sometimes requiring use of antiemetic and antidiarrheal medications. Ileus can occur. Fluid andelectrolyte replacement should be administered to prevent dehydration.

Thrombocytopenia/Neutropenia: VELCADE is associated with thrombocytopenia and neutropenia thatfollow a cyclical pattern with nadirs occurring following the last dose of each cycle and typically recoveringprior to initiation of the subsequent cycle. The cyclical pattern of platelet and neutrophil decreases andrecovery remained consistent over the 8 cycles of twice weekly dosing, and there was no evidence ofcumulative thrombocytopenia or neutropenia. The mean platelet count nadir measured was approximately40% of baseline. The severity of thrombocytopenia was related to pretreatment platelet count. In therelapsed multiple myeloma study, the incidence of significant bleeding events (≥Grade 3) was similar onboth the VELCADE (4%) and dexamethasone (5%) arms. Platelet counts should be monitored prior to eachdose of VELCADE. Patients experiencing thrombocytopenia may require change in the dose and scheduleof VELCADE. There have been reports of gastrointestinal and intracerebral hemorrhage in association withVELCADE. Transfusions may be considered. The incidence of febrile neutropenia was <1%.

Tumor Lysis Syndrome: Because VELCADE is a cytotoxic agent and can rapidly kill malignant cells, thecomplications of tumor lysis syndrome may occur. Patients at risk of tumor lysis syndrome are those withhigh tumor burden prior to treatment. These patients should be monitored closely and appropriateprecautions taken.

Hepatic Events: Cases of acute liver failure have been reported in patients receiving multiple concomitantmedications and with serious underlying medical conditions. Other reported hepatic events includeincreases in liver enzymes, hyperbilirubinemia, and hepatitis. Such changes may be reversible upondiscontinuation of VELCADE. There is limited re-challenge information in these patients.

Patients with Hepatic Impairment: VELCADE is metabolized by liver enzymes. VELCADE exposure isincreased in patients with moderate or severe hepatic impairment. These patients should be treated withVELCADE at reduced starting doses and closely monitored for toxicities.

ADVERSE EVENT DATA:

Safety data from phase 2 and 3 studies of single-agent VELCADE 1.3 mg/m2/dose twice weekly for 2weeks followed by a 10-day rest period in 1163 patients with previously treated multiple myeloma(N=1008, not including the phase 3, VELCADE plus DOXIL® [doxorubicin HCI liposome injection] study) andpreviously treated mantle cell lymphoma (N=155) were integrated and tabulated. In these studies, thesafety profile of VELCADE was similar in patients with multiple myeloma and mantle cell lymphoma.

In the integrated analysis, the most commonly reported adverse events were asthenic conditions (includingfatigue, malaise, and weakness); (64%), nausea (55%), diarrhea (52%), constipation (41%), peripheralneuropathy NEC (including peripheral sensory neuropathy and peripheral neuropathy aggravated); (39%),thrombocytopenia and appetite decreased (including anorexia); (each 36%), pyrexia (34%), vomiting (33%),anemia (29%), edema (23%), headache, paresthesia and dysesthesia (each 22%), dyspnea (21%), coughand insomnia (each 20%), rash (18%), arthralgia (17%), neutropenia and dizziness (excluding vertigo);(each 17%), pain in limb and abdominal pain (each 15%), bone pain (14%), back pain and hypotension(each 13%), herpes zoster, nasopharyngitis, upper respiratory tract infection, myalgia and pneumonia(each 12%), muscle cramps (11%), and dehydration and anxiety (each 10%). Twenty percent (20%) ofpatients experienced at least 1 episode of ≥Grade 4 toxicity, most commonly thrombocytopenia (5%) andneutropenia (3%). A total of 50% of patients experienced serious adverse events (SAEs) during the studies.The most commonly reported SAEs included pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%),and nausea, dehydration, dyspnea and thrombocytopenia (each 3%).

In the phase 3 VELCADE + melphalan and prednisone study, the safety profile of VELCADE in combination withmelphalan/prednisone is consistentwith the known safety profiles of both VELCADE and melphalan/prednisone.The most commonly reported adverse events in this study (VELCADE+melphalan/prednisone vsmelphalan/prednisone) were thrombocytopenia (52% vs 47%), neutropenia (49% vs 46%), nausea(48% vs 28%), peripheral neuropathy (47% vs 5%), diarrhea (46% vs 17%), anemia (43% vs 55%),constipation (37% vs 16%), neuralgia (36% vs 1%), leukopenia (33% vs 30%), vomiting (33% vs 16%),pyrexia (29% vs 19%), fatigue (29% vs 26%), lymphopenia (24% vs 17%), anorexia (23% vs 10%),asthenia (21% vs 18%), cough (21% vs 13%), insomnia (20% vs 13%), edema peripheral (20% vs 10%),rash (19% vs 7%), back pain (17% vs 18%), pneumonia (16% vs 11%), dizziness (16% vs 11%),dyspnea (15% vs 13%), headache (14% vs 10%), pain in extremity (14% vs 9%), abdominal pain(14% vs 7%), paresthesia (13% vs 4%), herpes zoster (13% vs 4%), bronchitis (13% vs 8%),hypokalemia (13% vs 7%), hypertension (13% vs 7%), abdominal pain upper (12% vs 9%), hypotension(12% vs 3%), dyspepsia (11% vs 7%), nasopharyngitis (11% vs 8%), bone pain (11% vs 10%),arthralgia (11% vs 15%) and pruritus (10% vs 5%).

DRUG INTERACTIONS:

Co-administration of ketoconazole, a potent CYP3A inhibitor, increased the exposure of bortezomib.Therefore, patients should be closely monitored when given bortezomib in combination with potent CYP3A4inhibitors (e.g. ketoconazole, ritonavir). Co-administration of melphalan-prednisone increased the exposureof bortezomib. However, this increase is unlikely to be clinically relevant. Co-administration of omeprazole,a potent inhibitor of CYP2C19, had no effect on the exposure of bortezomib. Patients who are concomitantlyreceiving VELCADE and drugs that are inhibitors or inducers of cytochrome P450 3A4 should be closelymonitored for either toxicities or reduced efficacy.

USE IN SPECIFIC POPULATIONS:

Nursing Mothers: It is not known whether bortezomib is excreted in human milk. Because many drugs areexcreted in human milk and because of the potential for serious adverse reactions in nursing infants fromVELCADE, a decision should be made whether to discontinue nursing or to discontinue the drug, taking intoaccount the importance of the drug to the mother.

Pediatric Use: The safety and effectiveness of VELCADE in children has not been established.

Geriatric Use: No overall differences in safety or effectiveness were observed between patients ≥age 65 andyounger patients receiving VELCADE; but greater sensitivity of some older individuals cannot be ruled out.

Patients with Renal Impairment: The pharmacokinetics of VELCADE are not influenced by the degree of renalimpairment. Therefore, dosing adjustments of VELCADE are not necessary for patients with renal insufficiency.Since dialysis may reduce VELCADE concentrations, the drug should be administered after the dialysisprocedure. For information concerning dosing of melphalan in patients with renal impairment, seemanufacturer's prescribing information.

Patients with Hepatic Impairment: The exposure of VELCADE is increased in patients with moderate andsevere hepatic impairment. Starting dose should be reduced in those patients.

Patients with Diabetes: During clinical trials, hypoglycemia and hyperglycemia were reported in diabeticpatients receiving oral hypoglycemics. Patients on oral antidiabetic agents receiving VELCADEtreatment may require close monitoring of their blood glucose levels and adjustment of the dose of theirantidiabetic medication.

VELCADE, MILLENNIUM and are registered trademarks of Millennium Pharmaceuticals, Inc.Other trademarks are property of their respective owners.Millennium Pharmaceuticals, Inc., The Takeda Oncology Company. Cambridge, MA 02139Copyright ©2009, Millennium Pharmaceuticals, Inc.

Brief Summary

All rights reserved. Printed in USA V1215 12/0910V-10-020410

Cambridge, MA 02139

5www.AHDBonline.comVOL. 4 NO. 1 SPECIAL ISSUE

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Editor-in-ChiefRobert E. [email protected]

Mission StatementAmerican Health & Drug Benefits is founded on theconcept that health and drug benefits have undergonea transformation: the econo metric value of a drug is ofequal importance to clinical outcomes as it is to serv-ing as the basis for securing coverage in formulariesand benefit designs. Benefit designs are greatly affect-ed by clinical, business, and policy conditions.

This publication provides benefit design de cisionmakers the integrated industry information theyrequire to devise formularies and benefit designs thatstand up to today’s special healthcare delivery andbusiness needs.

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American Health & Drug Benefits, ISSN 1942-2962(print); ISSN 1942-2970 (online), is published 6times a year by Engage Healthcare Communica -tions, LLC, 241 Forsgate Drive, Suite 205A, MonroeTownship, NJ 08831. Copyright © 2011 by EngageHealthcare Communications, LLC. All rightsreserved. American Health & Drug Benefits and ThePeer-Reviewed Forum for Evidence in Benefit Designare trademarks of Engage Healthcare Communi -cations, LLC. No part of this publication may bereproduced or transmitted in any form or by anymeans now or hereafter known, electronic ormechanical, including photocopy, recording, or anyinformational storage and retrieval system, withoutwritten permission from the Publisher. Printed inthe United States of America.

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EDITORIAL BOARD

ASH 2010: PAYERS’ PERSPECTIVESAMERICAN SOCIETY OF HEMATOLOGY HIGHLIGHTS

CLINICAL EDITOR Thomas G. McCarter, MD, FACPChief Clinical OfficerExecutive Health Resources, PA

GOVERNMENT EDITORKevin B. “Kip” Piper, MA, FACHEPresident, Health Results GroupSr. Counselor, Fleishman-Hillard Washington, DC

ACTUARY David WilliamsMilliman Health ConsultantWindsor, CT

AGING AND WELLNESSEric G. Tangalos, MD, FACP, AGSFProfessor of MedicineMayo Clinic, Rochester, MN

CANCER RESEARCHAl B. Benson, III, MD, FACPProfessor of MedicineAssociate Director for Clinical InvestigationsRobert H. Lurie Comprehensive CancerCenter, Northwestern UniversityPresident, ACCCPast Chair, Board of Directors, NCCN

Samuel M. Silver, MD, PhD, FACPProfessor, Internal MedicineDirector, Cancer Center NetworkDivision of Hematology/OncologyAssistant Dean for ResearchUniversity of Michigan Health Systems

CARDIOLOGY RESEARCH Michael A. Weber, MDProfessor of MedicineDepartment of Medicine (Cardiology)State University of New York

ENDOCRINOLOGY RESEARCHJames V. Felicetta, MD Chairman, Dept. of Medicine Carl T. Hayden Veterans AffairsMedical Center, Phoenix, AZ

EMPLOYERSAlberto M. Colombi, MD, MPHCorporate Medical DirectorPPG Industries, Pittsburgh, PA

Wayne M. Lednar, MD, PhDGlobal Chief Medical OfficerDirector, Integrated Health ServicesDuPont, Wilmington, DE

Arthur F. Shinn, PharmD, FASCPPresident, Managed Pharmacy Consultants, Lake Worth, FL

F. Randy Vogenberg, RPh, PhDPrincipal, Institute of Integrated HealthcareSharon, MA

EPIDEMIOLOGY RESEARCHJoshua N. Liberman, PhD Vice President, Strategic Research CVS Caremark, Hunt Valley, MD

HEALTH INFORMATION TECHNOLOGY J. B. Jones, PhD, MBAResearch Associate, Geisinger Health System, Danville, PA

Victor J. Strecher, PhD, MPHProfessor and Director, Center for HealthCommunications ResearchUniversity of Michigan Schools of PublicHealth and Medicine, Ann ArborFounder and Chief Visionary OfficerHealthMedia, Johnson & Johnson Co.

HEALTH OUTCOMES RESEARCH Diana Brixner, RPh, PhDProfessor and ChairDepartment of PharmacotherapyExecutive Director Outcomes ResearchCenter, University of Utah College ofPharmacy, Salt Lake City

Gordon M. Cummins, MSDirector, IntegriChain

Kavita V. Nair, PhDAssociate Professor, School of PharmacyUniversity of Colorado at Denver

Gary M. Owens, MDPresident, Gary Owens AssociatesGlen Mills, PA

Timothy S. Regan, BPharm, RPhExecutive Director, XcendaPalm Harbor, FL

MANAGED CARE & GOVERNMENT AFFAIRSSharad Mansukani, MDChief Strategic Officer, Nations HealthSenior Advisor, Texas Pacific Group, FL

MANAGED MARKETS Jeffrey A. Bourret, RPh, MS, FASHPSenior Director, Branded Specialty PharmacyPrograms, US Specialty Customers Pfizer,Specialty Care Business Unit, PA

Charles E. Collins, Jr, MS, MBAVice President, Managed Markets StrategyFusion Medical Communications

PATIENT ADVOCACY William E. Fassett, BSPharm, MBA, PhDProfessor of Pharmacy Law & EthicsVice Chair, Dept. of PharmacotherapyCollege of Pharmacy, Washington StateUniversity, Spokane, WA

PERSONALIZED MEDICINE Wayne A. Rosenkrans, Jr, PhDChairman and President, Personalized Medicine Coalition, Distinguished Fellow,MIT Center for Biomedical Innovation

PHARMACOECONOMICSJeff Jianfei Guo, BPharm, MS, PhDAssociate Professor of Pharmacoeconomics& Pharmacoepidemiology, College of Pharmacy, University of Cincinnati Medical Center, OH

PHARMACY BENEFIT DESIGN Joel V. Brill, MDChief Medical Officer, Predictive Health, Phoenix, AZ

William J. Cardarelli, PharmDDirector of PharmacyAtrius HealthHarvard Vanguard Medical Associates

Leslie S. Fish, PharmDSr. Director of Pharmacy ServicesFallon Community Health Plan, MA

Michael S. Jacobs, RPhNational Clinical Practice LeaderBuck Consultants, Atlanta

Matthew Mitchell, PharmD, MBAManager, Pharmacy ServicesSelectHealth, Salt Lake City, UT

Paul Anthony Polansky, BSPharm, MBASenior Field Scientist, Health Outcomes andPharmacoEconomics (HOPE) Endo Pharmaceuticals Inc., Chadds Ford, PA

Scott R. Taylor, RPh, MBAAssociate Director, Industry RelationsGeisinger Health System, Danville, PA

POLICY & PUBLIC HEALTH Joseph R. Antos, PhDWilson H. Taylor Scholar in Health CareRetirement PolicyAmerican Enterprise Institute

Jack E. Fincham, PhD, RPh Professor of Pharmacy, School of PharmacyUniversity of Missouri, Kansas City

Alex Hathaway, MD, MPH, FACPMPresident & Founder, J.D. BioEdgeHealth quality and biomedical research consultancy

J. Warren Salmon, PhDProfessor of Health Policy & AdministrationSchool of Public HealthUniversity of Illinois at Chicago

REIMBURSEMENT POLICYGrant D. Lawless, BSPharm, MD, FACPExecutive Director for Payor RelationsCorporate Account, Amgen, CA

RESEARCH & DEVELOPMENT Michael F. Murphy, MD, PhDChief Medical Officer and Scientific Officer Worldwide Clinical TrialsFaculty, Center for Experimental Pharmacology and Therapeutics, Harvard-MIT Division of Health Sciences andTechnology, Cambridge, MA

SPECIALTY PHARMACYAtheer A. Kaddis, PharmDVice President, Managed MarketsDiplomat Specialty PharmacySwartz Creek, MI

James T. Kenney, RPh, MBAPharmacy Operations Manager Harvard Pilgrim Health Care, Wellesley, MA


VOL. 4 NO. 1 SPECIAL ISSUE6 AMERICAN HEALTH & DRUG BENEFITS February 2011

Health Economics

The prophylactic use of recombinant human granulocytecolony-stimulating factor (G-

CSF)—including filgrastim daily forup to 2 weeks per chemotherapy cycleand pegfilgrastim once per cycle—decreases the incidence of febrile neu-tropenia and is a well-establishedstrategy. Cancer delivery models,however, are under pressure tobecome more efficient in an increas-ingly cost-restrictive environment,said Douglas Taylor, of i3 Innovus,Medford, MA. “Little is known regarding the use of

practice resources necessary to deliver

therapy. We constructed an empiricalmodel to calculate the human resourcetime and cost associated with thedelivery of filgrastim and pegfilgras-tim,” Mr Taylor said.The study team used a practice-

level model to detail staff tasksrequired during 1 month in adminis-tering G-CSF. Specific clinic character-istics were included (eg, number ofpatients receiving G-CSF, number offilgrastim injections per cycle, hourlypay rates for staff). The study team interviewed 400

medical professionals at 20 US com-munity oncology practices to provide

data for the time and personnelrequired for tasks, such as scheduling,front desk, phlebotomy, laboratory,triage, injection, and billing.

The costs of the drugs were notincluded in the model. The case-based

scenarios contrasted 1 patient versus 30patients per month. The use of pegfilgrastim resulted in

substantial savings in a comparisonwith filgrastim given as either 6 or 11injections per cycle and in scenariosbased on 1 or 30 patients per month(Table). The 30-patient model predict-ed that monthly costs were more favor-able with pegfilgrastim than with 6 and11 days of filgrastim, respectively:• Staff hours were reduced from 756to 378

• Staff costs were reduced from$18,000 to $9000.

On a per-patient basis, the monthlyopportunity costs were more favorablefor pegfilgrastim than for filgrastim,respectively:• Staff hours were reduced from 25to 13 hours

• Staff costs were reduced from $600to $300.

“The use of pegfilgrastim as com-pared with filgrastim was associatedwith substantial savings in time andlabor costs,” Mr Taylor said, acknowl-edging that the model did not includethe cost of purchasing the drugs. “Wethink that future medical care deliv-ery models should consider practiceresource requirements as a means of increasing efficiency and cost-effectiveness.” �

Pharmacoeconomics: Hematologists Should Prepare... Continued from page 1

advocate, not bean counters, he said.Yet Dr Mikhael insists that to be com-pletely oblivious to drug cost is to do adisservice to other patients and to soci-ety at large.“It’s not about saying that a cancer

drug is too expensive, therefore, it isnot cost-effective. That’s not the point,”Dr Mikhael pointed out. Rather, theprice has to be considered within thecontext. He explained pharmacoeco-nomics as defining the context, quanti-fying the spectrum of effects experi-enced by an average patient with agiven drug, and putting a dollaramount to the overall outcome.How to derive this figure is the

focus of many of Dr Mikhael’s consid-erations when thinking about limitedhealthcare budgets. The key is to use a method that

accounts for the quantity of a thera-peutic response (eg, delayed diseaseprogression), the patient’s quality oflife (QOL) during treatment, and, ofcourse, the financial cost. Furthermore,this calculation must be applicableacross all disease states. “The goal ofhealth economics is to provide infor-

mation to key stakeholders so they canmake decisions in the context of evi-dence-based medicine and policy,”said Dr Mikhael.

To this end, there is the determinantof quality-adjusted life-year (QALY). Inbrief, a QALY is a single unit measurethat factors in life expectancy and thequality of those remaining years.Derived with already validated QOLinstruments, a QALY is then expressedas a single number (1 = a year of per-fect health; 0 = death). Differingnumeric weights are assigned to dif-fering health states, thereby account-ing for pain and suffering. For example, with intervention A,

the patient has 4 years of life in ahealth state of 0.75, or 3 QALYs; withintervention B, 4 years in a healthstate of 0.5 is equal to 2 QALYs. Atthis point, cost is not related to thisexpression of efficacy, and “whatmost people want to hear is the ICER[incremental cost-effectiveness ratio],”he said. The ICER is the ratio of change in

cost to the change in effect. Expressedas a dollar amount, and historicallyset as the cost of treating a patientwith dialysis for 1 year, it is how, com-bined with QALY, the “worth” of agiven intervention is perceived. Of

note, this value is not comparativeacross nations; the threshold of“worth” in the United Kingdom isapproximately $35,000 per QALY; inthe United States, it is roughly$100,000 per QALY. “QALY is an expression of what we

as a society are willing to pay for,given the result,” he said.As yet, payers in the US healthcare

system cannot refuse reimbursementbased on the above calculation. It isprimarily used now as a marketingtool, illustrating “bang for the buck.”But as stated by Dr Mikhael, “This isreal science, and like it or not, it’s com-ing to a theater near you.” It is critical that healthcare pro -

viders, who often do not even feelequipped to have such discussions,familiarize themselves with the termsof the coming debate, Dr Mikhaelemphasized. Future therapies willlikely have to prove themselves—togovernments, to payers, and topatients—to be cost-effective. “If weas clinicians bury our heads in thesand, someone else is going to deter-mine how we practice.” �

“The goal of healtheconomics is to provideinformation to keystakeholders so they canmake decisions in thecontext of evidence-basedmedicine and policy.”

—Joseph Mikhael, MD

Labor Costs Reduced with Pegfilgrastim versus Comparator By Caroline Helwick

Table Monthly Time and Cost-Savings of Using Pegfilgrastim Compared with Filgrastim

Prophylaxis strategyFilgrastim, treating

1 patient/moOnce-per-cycle

pegfilgrastim injectionFilgrastim, treating30 patients/mo

Once-per-cycle pegfilgrastim injection

Filgrastim injections/cycle, N 6 11 6 11

Nurse hrs, N 9.4 17.3 1.5 283 519 45

Clerk hrs, N 5.7 10.4 0.9 170 311 28

Total hrs, N 15.1 27.7 2.5 453 830 75

Opportunity cost with pegfilgrastim,a hrs 12.6 25.2 378 756

Cost, $ 365 668 60 10,945 20,066 1795

Opportunity cost with pegfilgrastim,a $ 305 609 9151 18,271

aFilgrastim minus pegfilgrastim.

“Future medical care deliverymodels should considerpractice resourcerequirements as a means of increasing efficiency.”

—Douglas Taylor


Health Economics

Most spending goes toward hospitalcare and physician services, whichcomprise about 10% of the total health-care cost.“We are not getting tremendous

healthcare outcomes for all thismoney,” said Dr Emanuel, himself anoncologist, who was the invitedspeaker on healthcare reform at ASH2010. “Despite much higher spend-ing, the US ranks 12th [worldwide]for males and 16th for females in lifeexpectancy at age 65.”

Quality of Care Is an Issue inAmerica, Except in CancerIn terms of overall quality, cancer

care is an example of where quality inthe United States is high, Dr Emanuelacknowledged. The CONCORD study(Coleman MP, et al. Lancet Oncol.2008;9:730-756) looked at the quality ofcancer care in 31 countries, measuredby 5-year survival rates, and rankedthe United States second in breast can-cer, first in prostate cancer (but thismay reflect lead time bias), and thirdin colorectal cancer. Within the UnitedStates, there is substantial variation incancer outcomes.But guideline-defined care is fre-

quently not delivered, he said. TheRAND Corporation has found thatAmericans receive only 55% of rec-ommended care. Good disease con-trol has been noted for just 65% ofpatients with hypertension, 54% withasthma, and 39% with community-acquired pneumonia. “Quality of careis an issue for all Americans,” DrEmanuel said.

New Act Addresses Many Serious ProblemsThe Patient Protection and Afford -

able Care Act (ACA) aims to makethis situation better. Passage of theACA was a “world historical event,”having been attempted by 5 previouspresidents over 100 years beforebeing accomplished by the Obamaadministration. But despite its promise to increase

coverage to approximately 94% of theAmerican populace (resulting in 32million fewer uninsured persons), crit-icism has been abundant and therepeal efforts continue, he maintained.Some of this rancor may stem from

misinterpretations and myths aboutthe act, which Dr Emanuel set straightin his presentation.

Myth 1: The Reform Is 90% Coverageand Only 10% Cost Control“Healthcare reform will try almost

every major idea to reduce healthcarecosts....Many provisions will reduce

the amount of spending on health-care,” Dr Emanuel pointed out. Thegreatest reductions will come from thefollowing reductions in spending:• Reduction of payment update fac-tor ($196 billion)

• Cutting overpayment to MedicareAdvantage ($136 billion)

• Administrative simplification ($20billion)

• Use of generic biologics ($7 billion)• Enforcement of fraud and abuse($3 billion)

• Payment change for compleximaging procedures ($1.2 billion).

In addition, other provisions willslow the growth rate in spending,including the “Cadillac tax”; patient-centered outcomes research; hospital30-day admission policy (ie, penaltiesimposed when patients are readmittedas a result of inadequate care); reduc-tion in hospital-acquired infectionsand conditions; and the use of medicalhomes, accountable care organiza-tions, and bundled payments.

Myth 2: Even If Passed, the CostControl Provisions Will Never BeImplemented• Reducing payment for high-costimaging services is in the 2011Medicare physician fee schedule

• Reducing payment updates foroutpatient, hospital, and ambula-tory surgical centers is in the 2011Outpatient Hospital ProspectivePayment Rules

• Pay as you go compels Congressnot to add to the federal deficitwhen instituting new spending ortax changes.

Myth 3: Healthcare Reform WillCost Americans“Reform will not add to the budget

or budget deficit,” he emphasized,predicting more than $100 billion insavings by 2020. He noted that unlikeMedicare Part D, healthcare reform is“completely, totally paid for” withnew resources and offsets. “Healthcarereform is likely to be even cheaperthan anticipated if cost controls workand healthcare inflation is lower,reducing Medicare and Medi caid out-lays and subsidies,” Dr Emanueladded. “I think these reforms will havea synergistic effect.”

Myth 4: All the Important Parts ofReform Don’t Happen until 2014 or Later“This is partly true,” he acknowl-

edged. “But if hospitals, physicians,insurers, and others behave like myHarvard undergraduates, and waituntil the night before the due date and

pull an all nighter, they will fail andfail miserably.” Changes, therefore,were gradually initiated even beforethe ACA’s passage.

What Reform Will Mean for Cancer CareChanges in the healthcare delivery

system, including the field of oncolo-gy, will occur in 3 main areas: infor-mation (using new technologies, pri-marily financial incentives forinstalling electronic health records,and comparative effectiveness re -search), infrastructure (using medicalhomes and accountable care organi-zations), and incentives (using bun-dled payments and other financialand quality instruments). The ACA creates and funds the

Patient-Centered Outcomes ResearchInstitute to generate comparativeeffectiveness data. Up to $600 millionper year will be directed toward thiseffort, based on $2 per insured personper year. The institute has broad rep-resentation from researchers, physi-cians, nurses, drug and device com-panies, and insurers. “Initial research will be very impor-

tant to prevent politicization andcharges of rationing,” Dr Emanuelnoted. “The results will be a ‘publicgood.’ Get ready for a flood of data,”he told attendees. All these policies

aim to transform the delivery systemto produce more coordinated care, bet-ter tertiary prevention, reduced spe-cialty services and procedures, andreduced hospitalizations.Bundled payments may be the most

striking change oncologists will expe-rience, but Dr Emanuel put this in pos-itive terms. “We have lots of guide-lines, which will be used to determinebundled payments. This gives you flex-ibility in managing patients as you seefit to provide optimal care,” he said.Oncologists will benefit through

improved health information technol-ogy. They will have financial incen-tives to install interoperable electronichealth records that will enhancepatient care through meaningful use.Administrative tasks should be simpli-fied, and the burden and cost of billingshould decrease, Dr Emanuel said. “For your patients, healthcare re -

form means better efforts at preven-tion,” he pointed out. This includesbetter coverage of breast, colon, andcervical cancer screening tests with nocopays and the reduction and eventu-al elimination of the Medicare Part Ddoughnut hole. It will include a cam-paign for positive lifestyle changes.Patients with cancer will particularlybenefit through the elimination ofpreexisting conditions exclusions,and the elimination of rescissions and

“We are not getting tremendous healthcare outcomes for allthis money….Despite much higher spending, the US ranks12th [worldwide] for males and 16th for females in lifeexpectancy at age 65.”

—Ezekiel J. Emanuel, MD, PhD

Healthcare Reform Addresses... Continued from page 1

Continued on page 8

Offering a range of advice forsurvival in the challengingenvironment of recent and

ongoing healthcare reform, a panel ofphysicians and businessmen describedthe innovative means by which theyhave adapted their hospital-based prac-tices, multispecialty group practices,and single-specialty group practices. William C. Rupp, MD, Chief

Executive Officer of the Mayo Clinic,Jacksonville, FL, shared his experiencewith hospitals. “There is not going tobe more money in the system,” hesaid. “We’re going to have to figureout how to do what we do with themoney that’s out there.”And the money that is out there must

not be squandered; Dr Rupp estimatesthat 30% to 40% of operational costresults from waste. Recapturing thosedollars means delivering healthcare innew and innovative ways, and to dothat, the successful leader must foster aculture that is receptive to change.“The first thing you can do is give

up on the idea that you’re thesmartest person in the room,” he sug-gested. In Dr Rupp’s experience, thevast majority of viable, practice-changing ideas come from the front-line staff; they do the work, and theyoften know how best it can be done,he pointed out. Receiving a new idea may also

require listening to an unfamiliarvoice. Dr Rupp actively seeks out

diverse opinions. “I know when I sur-round myself with people who thinkthe way I do, I’m heading for financialdisaster.”

Implementing change requires ameasure of faith. For example, fre-quent monitoring of a task that has

been officially handed off is not dele-gating, it is micromanaging, he said. Dr Rupp also suggests that the fail-

ure of new processes should be “cel-ebrated.” “Go to your staff tomorrowand ask them for a list of thingsthey’ve tried in the last month thathave not worked,” he said. “If theycan’t give you a list, you’re not tryinghard enough to innovate.” He added that change does not

always necessitate new software, butis often implemented with a penciland paper. Nor should the testing ofinnovations be time-consuming. “I’veseen situations where a change wasrepeatedly tested over a period of 3months,” he said. “So I asked, ‘Were theresults any different at 3 months thanthey were at 1 week?’ Usually not.”

Large Single-Specialty PracticeThomas Marsland, MD, of Orange

Park, FL, shared specific measuresimplemented in his large, single-spe-cialty practice, many of which can bedescribed as pay attention to detail,he said. First, establish charge capture via an

audit. “If you miss billing for 1 dose ofProcrit, it will take 9 or 10 more admin-istrations to make up the difference inwhat you lost,” Dr Marsland pointedout. “Did you collect the copay? Didyou collect the coinsurance? That’smoney left on the table. In one auditwe found $100,000, and it was inthings that were easy to miss, like put-ting down 1 unit when it was really10—simple stuff.”Cost control begins at the first

patient encounter. “We’ve instituteda policy where every new patientmeets with a financial counselorbefore he receives any treatment, sothe patient knows what the copaywill be,” he said, adding that hisstaff makes the patient’s responsi-bilities clear and treats responsibly.“Our business office must sign offon a treatment program before itgoes to the nurse. This minimizesoff-label denials, which are increas-ingly common.”For the larger picture, Dr Marsland

summarized his strategy with thefamous line from the movie Jaws:“We’re going to need a bigger boat.”In today’s environment, he said, sizematters. To that end, Dr Marslandand colleagues expanded services,bringing on board radiation oncolo-gists, imaging equipment and staff,laboratory services, and so on. “Going forward we have to get

paid for what we do,” he empha-sized. “Profits from drugs are gone.We have to be reimbursed for man-aging and taking care of patients.”

Multispecialty Group PracticeStuart Feldman, MD, of White

Plains, NY, represented the multispe-cialty group practice. Having formeda group of 16 physicians in 1996, DrFeldman’s physician-owned organi-zation now employs 180 physiciansfrom 20 different specialties, who arehoused in 160,000 square feet of spacethat includes an ambulatory surgicalcenter, 2 urgent care centers, imagingfacilities, and a pathology laboratory—in other words, “a big boat.”“One-stop total healthcare keeps

patients coming through the door,”Dr Feldman told attendees. The sizeof the organization provides leveragewhen negotiating fees with carriers,and its structure is leveraged for syn-ergy (eg, radiation oncologists use in-house facilities); referrals to otherphysicians can all be retained withinthe organization. “These are profit centers,” Dr

Feldman stressed, “and the profits arethen distributed among the share-holders in the form of bonuses. This isa relatively new concept in physiciancompensation.”Of note, and as indicated by the first

question in the question and answersession, there was an 800-pound hema- tologist in the room: “Am I to under-stand from these presentations that pri-vate practice is dead?” The subject of the question and its

frustrated tone occupied the remain-ing minutes of the forum. The moder-ator, Lawrence A. Solberg Jr, MD, PhD,of the Mayo Clinic, Jacksonville, FL,fervently stated that it was not theAmerican Society of Hematology’sofficial position that private practiceshould be abandoned, but rather thatsolutions for private practice were notso obvious. He did advise thatalliances with state and/or regionalprofessional societies would be a goodfirst step. �


Health Economics

Healthcare Practice Forum: Survival Dependson InnovationBy Neil Canavan

“There is not going to be moremoney in the system. We’regoing to have to figure outhow to do what we do withthe money that’s out there.”

—William C. Rupp, MD

Healthcare Reform... Continued from page 7

the annual and lifetime limits. Theact also mandates coverage of rou-tine costs of clinical trials.

Oncologists Can Participate inLowering CostsThe oncology community has a big

role to play to enhance reform and topersonally benefit by it, he told attend -ees. “Oncologists should get theiroffices wired and use the financingthat is available for installing electron-ic medical records,” he said. “Youmust develop quality indicators thatgo beyond screening percentages, andthat extend to surgery, the delivery ofradiotherapy, and the delivery ofchemotherapy. We must also makesure these quality indicators can becollected electronically.”Physicians should also develop

treatment guidelines and protocolsthat incorporate criteria for lower costfor the same or better quality out-

comes, he added. “Where there arediagnostic and therapeutic optionsthat are equivalent, we should priori-tize by total cost and ease of use,” hesaid. “For palliative radiation therapy,we should use shorter courses oftreatment that are equivalent from theperspective of pain relief, less incon-venience for patients, and lower cost.”Bundled payments should also

be guideline-driven with physicianinput. These will be used by payers todetermine reimbursement for com-mon hematologic conditions such aslymphomas, sickle-cell disease, anti-coagulation therapy, and leukemias. In moving forward, the healthcare

community will be “fostering innova-tion, rethinking and modernizinghow we provide cancer care,” DrEmanuel said. “For 50 years, mostcare has been hospital-focused. We arerethinking this: continuity of careshould become the standard.” �

“Profits from drugs are gone.We have to be reimbursedfor managing and taking care of patients.”

—Thomas Marsland, MD

The Centers for Medicare &Medicaid Services (CMS)denies reimbursement for pre-

ventable hospital-acquired conditions,including venous thromboembolism(VTE) in patients undergoing a totalknee replacement or hip replacement/revision. In cases where the VTE is sec-ondary to hospital procedures, CMSreimburses the hospital only for thesurgical procedure. A study presentedat ASH 2010 suggests that this policymay not be cost-saving and, in fact,may cost hospitals about $8500 annu-ally in lost revenue per VTE diagnosis.The study used patient discharge

data from the Thomson ReutersMarketScan Hospital Drug Database,which contains hospital administrativedata from more than 580 acute-care hos-pitals in the United States. Frequency ofCMS-defined symptomatic VTE wasassessed among patients undergoingtotal knee re placement or hip replace-ment/revision. This included deep-veinthrombosis (DVT) and pulmonaryembolism (PE).

The analysis included 109 medium-to-large nonteaching hospitals inurban areas. The total number of sur-gical knee or hip discharges was26,144, with an average of 244 dis-charges per hospital. VTE occurred onaverage in 4.3 patient discharges perhospital. These included DVT in 2.4discharges and PE in 1.8 discharges.

Cost to the HospitalThe costs to the hospital accrue from

several areas. The mean length of hos-pital stay was 7.6 days for surgical kneeor hip discharges in which a VTEoccurred compared with 4.1 days indischarges without a VTE. In patientdischarges where DVT and PE hadoccurred, anticoagulant use wasrecorded in 94.7% and 89.1% ofpatients, respectively. The mean num-ber of days of anticoagulation was 5.1for DVT and 6.1 for PE, reported StevenDeitelzweig, MD, of Ochsner ClinicFoundation, New Orleans. The cost per discharge without a

DVT event was approximately $15,000,rising to nearly $18,000 when a DVToccurred. All factors considered, theincremental (additional) cost of theDVT per discharge was $6751. For PE,the costs were much greater, approach-ing $25,000, and resulting in an incre-

mental cost of $8092 when not prevent-ed, Dr Deitelzweig reported.“The CMS HAC [hospital-acquired

conditions] policy for VTE in patientsundergoing total knee replacement orhip replacement or revision, on aver-age, caused a loss of hospital revenue,”Dr Deitelzweig said. “When a VTE

event occurs, it is associated with highincremental hospital costs. Under thenew CMS HAC policy, these significantcosts will no longer be reimbursed.Subsequently, hospitals will be respon-sible for covering them.” “Therefore, reducing the incidence

of VTE through appropriate prophy-

laxis of at-risk patients is vital inorder for hospitals to lessen the eco-nomic burden associated with treat-ing VTE events,” Dr Deitelzweig sug-gested. “The drive to encouragehospitals to provide more efficientand effective healthcare is becomingparticularly relevant now.” �


Health Economics

Contact your GSK representative for additional information or visit www.ARZERRA.com.

©2010 The GlaxoSmithKline Group of Companies All rights reserved. Printed in USA. AZA228R0 January 2011

Announcing a NEW J-Code for ARZERRA

ARZERRA will have a permanent HCPCS code effective January 1, 2011

The new J9302 Code replaces miscellaneous HCPCS Codes J9999, J3590, J3490, and C9260 that most providers have used to bill for ARZERRA to date

HCPCS code

J9302

Effective

January 1, 2011

Description

Injection,ofatumumab, 10mg

ARZERRA® HCPCS Code J9302

CMS Policy on VTE Prophylaxis Places New Burden on HospitalsBy Caroline Helwick

“When a VTE event occurs, itis associated with highincremental hospital costs.”

—Steven Deitelzweig, MD


Health Economics

In the first national examination ofthe burden of in-hospital care forthrombotic microangiopathies, in -

vestigators from the Children’sHospital of Pittsburgh concluded thatthe disease costs the healthcare system$227.4 million annually. Although hos-pitalization rates have fallen over time,costs have increased significantly,reported Ashish Gupta, MD.Thrombotic microangiopathies are

a category of pathologies that resultin thrombosis in capillaries and arte-rioles. This process leads to thrombo-cytopenia and a variety of othersymptoms.Data were used from the Nation -

wide Inpatient Sample (NIS), a part ofthe Healthcare Cost and UtilizationProject. The NIS is the largest all-payer inpatient database in theUnited States and gives a stratifiedprobability sample of 20% of all hos-pital discharges among communityhospitals, Dr Gupta said.In 1997, estimated thrombotic micro -

angiopathy–related visits totaled 1.35per 100,000 population; this numberdecreased to 0.79 per 100,000 visits in2006. However, there was a steadyincrease in hospitalizations from 1997

to 2002, followed by a decreasingtrend from 2004 to 2006. The mortality rate resulting from

thrombotic microangiopathy wasreported to be 9.4% of total hospital-izations in 2006 compared with 8.8%

in 2003. Women were significantlymore affected than men across all age-groups and had a significantly higherrate of hospitalization (P <.01) in 2006compared with 1997. The mean duration of hospitaliza-

tion was 13.4 days in 2006, with anaverage hospital charge of $106,512per patient, which was a significantincrease from $88,079 in 2003 and$54,083 in 1997, Dr Gupta reported. The disease contributed to an

aggregate charge of $227.4 million tothe national healthcare cost in 2008compared with $210.3 million in 2003and $93.7 million in 1997. Hospitalcharges for therapeutic plasmaphere-sis for thrombotic microangiopathyincreased from $72.8 million in 2003to $88.15 million in 2006. “We are presenting the first

national data of the burden of in-hospital healthcare utilization ofthrombotic microangiopathies in theUnited States. These data suggestthat there has been a significantincrease in the cost of in-hospitalhealthcare utilization between 1997and 2006, representing a significantlength of stay and mortality,” DrGupta concluded.—CH �

Thrombotic Microangiopathies Total $227.4 Million AnnuallyFirst Ever In-Hospital Utilization Data for This Disease

“These data suggest that there has been a significant increase in the cost of in-hospital healthcare utilizationbetween 1997 and 2006, representing a significant length of stay and mortality.” —Ashish Gupta, MD

In patients with chronic myeloidleukemia (CML), the developmentof pleural effusions escalates cost

beyond the direct expense of treatingthe effusion, according to the AnalysisGroup, in association with re searchersfrom the University of Texas M. D.Anderson Cancer Center.Patients with CML plus pleural effu-

sions incurred significantly higherresource utilization and total health-care costs compared with those free ofpleural effusions, as a result of not onlythe management of the effusion butalso a higher use of medical servicesassociated with complicated CML.The substantial economic burden of

pleural effusion indicates a need forvigilant monitoring for its signs andsymptoms, the investigators suggest-ed. Especially, patients with CMLtreated with tyrosine kinase inhibitors(TKIs) (ie, imatinib, nilotinib, or dasa-tinib) who have cardiovascular dis-ease or hypertension would benefitfrom being closely monitored, becausethese conditions have been shown to

increase the risk of pleural effusions. “For CML, the standard of care is

oral TKIs, but pleural effusions can bean adverse event related to this treat-ment. This requires medical care, may

compromise the course of CML treat-ment, and has economic conse-quences….Much of the costs relatesto the need to interrupt TKI treat-ment,” said Annie Guerin, MSc, whopresented the data at the meeting. The cost of managing TKI-associat-

ed pleural effusions has been estimat-ed to be $2062 to $2700 and from $6400to $9000 when an invasive procedure

is necessary. But these costs are proba-bly underestimates, Ms Guerin said,because they do not take into accountthe impact of CML on TKI treatment.The current study aimed to consider

the full economic burden. The study was based on the Ingenix

Impact and Medstat MarketScan ad -ministrative claims databases, whichtogether represent 85 million individu-als in 176 health plans. Investigatorsmatched characteristics between pa -tients with CML treated with a TKIwho developed pleural effusions (n =186) and those who did not (n = 186).

The propensity score was calculated onall relevant available demographic anddisease information. The patients with effusions used

significantly more resources and in -curred significantly more costs. Afteradjusting for confounding factors,patients with effusions had more all-cause CML-related inpatient daysand admissions, outpatient visits,other medical services, and emer-gency care visits. “Patients with pleural effusions

had about 3 times more inpatientadmissions, and 6 times more inpa-tient days,” she said. This led to significantly greater

healthcare costs; over 6 months, thetotal healthcare cost was $105,715 for apatient with pleural effusions versus$49,621 for one without. Total CML-related costs were $67,879 versus$32,892, respectively.“Patients with pleural effusions

had an adjusted incremental cost dif-ference of $43,668 over 6 months,” MsGuerin noted. �

Economic Analysis of Pleural Effusionsin CMLBy Caroline Helwick

“Patients with pleural effusions had about 3times more inpatient admissions, and 6times more inpatient days….[They] had an adjusted incremental cost difference of$43,668 over 6 months.” —Annie Guerin, MSc

SEE ALSO Leukemias, pages 16-18.


Health Economics

Highlighted during a press con-ference at ASH 2010, 2 studiesaddressed long-standing ques-

tions regarding stem-cell transplanta-tion. In the first study—presented byAlexander Schmidt, MD, PhD, of theDKMS German Bone Marrow DonorCenter, Tubingen, Germany—anattempt was made to settle the recent-ly raised issue regarding the long-term safety of hematopoietic stem-celldonation by individuals who areunrelated to the patient.“This is a somewhat unusual circum-

stance in that it is an altruistic act bydonors; therefore, donor safety is of thehighest importance,” Dr Schmidt said. To evaluate the long-term safety of

such transplantation, Dr Schmidt andcolleagues surveyed 15,456 individualswho had donated peripheral blood

stem cells or bone marrow beforeJanuary 2010. The rate of return forthe questionnaire exceeded all expec-tations, with more than 12,000 (81%)individuals responding. The results reflected 55,299 observa-

tional years after transplantation, mak-ing it the largest-ever donor follow-upstudy. Overall, the donors were foundto be in excellent health, the donorgroups were generally equally healthy,and the rate of malignancies was nohigher than expected in the generalpopulation. Dr Schmidt emphasized the low

risk for malignancy. This issue wasfirst mentioned in the British Journal ofHaematology (Bennett CL, et al. 2006;135:642-650), which expressed con-cern that the use of granulocytecolony-stimulating factor for stem-cell mobilization might increase therisk for developing hematologicmalignancies. As the story circulatedand anxiety grew in the community,the need to respond to the articlebecame clear.

Dr Schmidt said that these un -founded concerns have been put torest by these new findings. The sur-vey also documented that 95% ofrespondents indicated their willing-ness to donate again.

Double Up on Cord Blood, but atWhat Cost?A second study, presented by

Vanderson Rocha, MD, PhD, focusedon the amount of cord blood requiredin the setting of acute leukemia. “Cordblood transplantation is an importantoption, and one that is being activelypursued in the United States because ofthe need for racially diverse donors,”Dr Rocha said. Approximately 30% of patients in

need of transplantation lack a well-matched, unrelated adult peripheralblood stem-cell donor. Experience hassuggested that with cord blood, matchcriteria need not be as stringent. Oncecord blood is obtained, however, thequestion arises, “What works better, 1or 2 units?”“A favorable outcome depends on

the number of cells transplanted,” hesaid. The minimum threshold is 2.5 ¥107 cells/kg; below this number, mor-tality risk is very high. “Early effortsdemonstrated higher graft-versus-host disease,” said Dr Rocha, “butlower relapse rates were the result.”Dr Rocha retrospectively assessed

the outcomes of 377 single-unit and270 double-unit cord blood recipients.Although there was a significantincrease in acute graft-versus-host dis-ease in the double-unit cohort, ratesfor 2-year incidence of relapse inpatients in their first complete remis-sion favored the use of 2 units. The results of the study clearly

demonstrated the use of 2 units, but theutility of the observation is problematic:a single unit of cord blood costs up -ward of $35,000, Dr Rocha said. Commenting on the issue at a press

conference, Joseph Antin, MD, Chief,Stem Cell Transplantation Program,Harvard Medical School, said, “Alltransplantation is expensive, but cordblood is much more so because of thecost recovery that’s required from thecord banks.” Typing cord blood is expensive, as

are storage and the related administra-tion aspects. Because transplantationsare relatively rare, cord blood banksmust keep a large inventory to sell justa few units. “We were thinking aboutputting up a cord blood bank inMassachusetts, but it was estimated totake 10 years to break even at the cur-rent costs,” Dr Antin said. �

Stem-Cell Transplantation: Safety, Economic ConcernsBy Neil Canavan

The current standard therapyfor patients with pulmonaryembolism (PE) is initial inpa-

tient treatment with low-molecular-weight heparin (LMWH). However,several 2008 case studies highlightedin the American College of ChestPhysicians Antithrombotic TherapyGuidelines suggest that outpatienttreatment for PE is potentially safeand effective. The guidelines, how-ever, lack easy-to-use criteria forselecting candidates for outpatienttreatment. Reporting their findingsat the late-breaking trials session,the Hestia study investigators pro-posed just such criteria (Table). In an investigation that involved

multiple treatment centers in theNetherlands, 338 patients withacute PE were triaged with the pre-defined Hestia criteria for eligibility

for outpatient treatment startingwith therapeutic weight-adjusteddoses of LMWH. Individuals select-ed for outpatient care (n = 297) weresent home either immediately orwithin 24 hours after the diagnosisof PE. At 6 weeks, patients wererescreened with the Hestia criteriaand monitored for recurrent venousthromboembolism (VTE) or majorbleeding at 3 months.Only 2% of the evaluable patients

had a recurrence of VTE, and only0.7% had a major bleed. Theseresults compared favorably to his-torical rates for outpatients, estimat-ed at up to 6.2% for VTE and asmuch as 1.2% for major bleeding,noted Wendy Zondag, MD, ofLeiden University Medical Centre inthe Netherlands.“Outpatient treatment was at

least as effective as treatment ofpatients in the hospital,” Dr Zondagsaid. Although she did not state it out-

right, the potential savings by avoid-ing hospitalization costs are clearlyimplied for this strategy.—NC �

New Outpatient Treatment Criteria for PulmonaryEmbolism Can Cut Expenses

Table Hestia Study Criteria

Question Responsea

Patient hemodynamically unstable Yes/NoThrombolysis or embolectomy necessary Yes/NoActive bleeding or high risk for bleeding Yes/No>24 hours of oxygen supply to maintain oxygen saturation >90% Yes/NoPulmonary embolism diagnosed during anticoagulant treatment Yes/NoSevere pain needing intravenous pain medication >24 hours Yes/NoTreatment in the hospital >24 hours Yes/NoCreatinine clearance <30 mL/min Yes/NoSevere liver impairment Yes/NoCurrently pregnant Yes/NoDocumented history of heparin-induced thrombocytopenia Yes/NoaIf one of the questions is answered with YES, the patient cannot be treated at home in the Hestia study.

Alexander Schmidt, MD, PhD

“All transplantation is expensive, but cord blood is much more so because ofthe cost recovery that’s required from the cord banks.”

—Joseph Antin, MD


Health Economics

Rasburicase is a recombinant urateoxidase approved for the preven-tion of tumor lysis syndrome, an

oncologic emergency that leads to a hostof metabolic disturbances that can resultin acute renal failure and death.Currently, rasburicase is US Food andDrug Ad ministration (FDA)-approvedfor the management of hyperuricemiain patients with malignancies and canprevent tumor lysis syndrome. Inadults, the recommended dose is 0.2mg/kg intravenously daily for up to 5days, which translates into >$5100 fortreatment of a 75-kg person. At ASH2010, several studies suggested thatlower doses can be just as effective, andthe cost saved would be substantial.

Low Dose versus Standard DoseInvestigators from the Mayo Clinic,

Rochester, MN, evaluated the effec-tiveness of the 0.1-mg/kg dose com-pared with the recommended dose inthe prevention of tumor lysis syn-drome. The population included allpatients with a hematologic or onco-logic diagnosis (N = 125) between 2003and 2009 who received rasburi case onthe first day of chemotherapy. Thedrug was dosed at either 0.1 mg/kg(low dose) or 0.2 mg/kg (standard

dose) because of variations in practice.Rasburicase was repeated as neces-

sary. Additional doses were required in14.6% of the low-dose patients and21.4% of the standard-dose patients,which was not a significant difference. Although reduction in uric acid

was higher with the standard dose(97.1% vs 88.7%; P = .002), renal out-comes were similar.

“The low-dose patients received anaverage of 6 mg per dose versus 12 mgin the standard group. This representsa savings of $2601 per patient,” saidAflonso Eirin, MD. For a 75-kgpatient, treatment with the standarddose costs $6504, whereas the reduceddose costs only $3252 per treatment. Renal insufficiency was noted only in

the standard-dose patients: 7.4% versus0% (P = .05). Rates of dialysis were sim-ilar between the low-dose (7.3%) andstandard-dose (18.6%) groups (P = .07).Dialysis was often initiated for hyper-kalemia and hyperphosphatemia. Only12.5% of doses were started for eleva-tions in serum creatinine. “Our results suggest that low-dose

rasburicase may be as effective as 0.2mg/kg. Although high-dose rasburicase was more effective at reducing uricacid, it did not reduce the need for dial-

ysis, because dialysis was often precip-itated for hyperkalemia and hyper-phosphatemia, which rasburicase doesnot affect,” Dr Eirin said. “Despite bias,our results suggest low-dose rasburicase may be a viable alternative and thepotential savings could be enormous.”

Single-Dose Approach Effectiveand Less ExpensiveSince rasburicase came to market,

various studies have examined singledoses (3 mg and 6 mg) in the adultpopulation in an effort to find a dosingregimen that is as effective as the FDA-approved dose but is less expensive. A single-center study evaluated a

4.5-mg dose for its ability to lower uricacid levels versus the conventionalweight-based approach and to deter-mine its cost-effectiveness (Table). The results were reported by

Barbara Yim, PharmD, BCOP, of theJohn H. Stroger, Jr. Hospital of CookCounty, Chicago. “The cost of rasburicase is a prob-

lem for us. We found that using a sin-gle dose could save our hospital a lotof money,” Dr Yim commented. The retrospective study included 25

patients with hematologic malignan-cies receiving chemotherapy or plan-ning to initiate chemotherapy within24 hours of rasburicase administra-tion. Patients at low risk for tumorlysis syndrome were excluded.A total of 30 hyperuricemic events

occurred, and 93% of these were suc-cessfully managed with the single doseof rasburicase. Three patients requireda second dose to achieve response.Responders were defined as patientsachieving >50% reduction in the uricacid level at 24, 48, or 96 hours. �

Economic Benefits of Novel Dosing for RasburicaseBy Caroline Helwick

Table Costa of Single-Dose versus Weight-Based Rasburicase

Dosing Cost per patient, $ Total cost (30 events), $ Total savings, $

Single 4.5-mg dose regimen 1919 53,549

906,106FDA-approved 5-day regimen 31,988 959,655

aCost is calculated using August 2010 AmeriSource Bergen Bluebook average wholesale price. One 1.5-mg vial of rasburicase costs $639.77. For a 75-kg patient dosed at 0.2 mg/kg, the costs would beapproximately $6397 and $31,988 for a 1-dose and 5-day therapy, respectively.FDA indicates US Food and Drug Administration.

“The cost of rasburicase is a problem for us. We found thatusing a single dose could save our hospital a lot of money.”

—Barbara Yim, PharmD, BCOP

Publications of cost-effectivenessanalyses (CEAs) presented atannual meetings of the American

Society of Hematology (ASH) werefound to be few, of suboptimal quality,and largely industry-sponsored, ac -cord ing to a study presented at ASH2010 by Lee Mozessohn, MD, of theUniversity of Toronto. Dr Mozessohn and colleagues

examined ASH abstracts from 1997 to2007 that focused on malignanciesand reported outcomes in eitherincremental cost-effectiveness ratios(ICERs) or quality-adjusted life-years(QALYs), both adjusted to US dollars.To assess the quality of reporting,

indicators associated with well-per-formed CEAs were derived from liter-ature standards. The subsequent pub-lication of an abstract was establishedwith a MEDLINE search, and time topublication was determined usingKaplan-Meier analysis. (Author affili-ation was also extracted.)A total of 29 abstracts met inclusion

criteria. Of those, only 13 were subse-quently published (44.8%), of whichall but 1 had determined an ICERbelow the accepted cost-effectivenessthres hold of $100,000/QALY for thestudy regimen (median $33,000/QALY). “Most of the studies we looked at

from ASH over the 10-year period were

quite favorable in terms of the cost-effectiveness ratio,” Dr Mozessohn saidin an interview. Overall, 55.2% of abstracts indicat-

ed industry sponsorship, and for theyears after 2001, when ASH instituteda policy of disclosure reporting, therate was 72.7%. The indicators ofreporting a societal perspective, life-time horizon, or sensitivity analysiswere noted in only 37.9%, 24.1%, and62.1% of abstracts, respectively. No quality indicator predicted time

to publication; however, abstractsreporting favorable ICERs had a moretimely publication, although thistrend was not significant.

Dr Mozessohn concluded that,although there was no direct evidenceof bias in ASH abstracts selected forpublication, most reported very favor-able ICERs, and the authors were con-sistently affiliated with the pharma-ceutical industry.Cost-analyses are clearly needed,

especially in these days of compara-tive effectiveness research. However,with the current economic situation, itis unlikely to get funding for suchanalyses from independent or publicgroups. Complete transparency offinancial support or potential conflictof interest is therefore key to ensuringthe quality of such research. �

Are Cost Analyses Presented at ASH Shortchanged?By Neil Canavan


Rituximab has become an indis-pensable agent in the treatmentof non-Hodgkin lymphoma

(NHL). At ASH 2010, several inves-tigative groups reported data on vari-ous combinations using this very effec-tive agent. The Groupe d’Etude des Lymph -

omes de l’Adulte (GELA) studylooked at the use of rituximab in combination with a reduced-dose ver-sion of CHOP (cyclophosphamide,Adriamycin [doxorubicin], vincristine,and prednisolone; R-mini-CHOP) forpatients with lymphoma who wereaged ≥80 years. This age-group repre-sents a growing number of patientswith NHL.“In Western Europe, an 80-year-old

man presently has a remaining 9.5years of life expectancy,” saidFrederic Peyrade, MD, of the CentreAntoine Lacassagne, Nice, France.“That means that by 2050, there willbe twice as many individuals in thisage bracket as there are now—andthat will represent greater than 15% ofthe overall population.”

GELA enrolled 149 patients withtreatment-naïve, diffuse large B-celllymphoma. The scheduled treatmentfor GELA was R-mini-CHOP every 21days for 6 cycles. After a median fol-low-up of 20 months, the overallresponse rate was an impressive 74%,with 40% of patients having a com-plete response; this success translatedinto a 2-year survival rate of 59%. Despite the observed discontinua-

tion rate (n = 41) for various reasons,serious life-threatening toxicities(grade 3-4) were not common andgenerally occurred within the firsttreatment cycle. Commenting onthese robust responses, Dr Peyradestated, “It means that even with thesevery old patients, obtaining the bestresponse possible remains crucial interms of overall survival.” In general, he said, these results

indicate that even elderly patients(≥80 years) should be considered fortreatment.

Rituximab/Bendamustine versusRituximab/FludarabineUnder the guidance of Mathias J.

Rummel, MD, PhD, of Klinikum derJustus-Liebig Universität, Giessen,

Germany, the Study Group of IndolentLymphomas (StiL) reported finalresults for NHL 2-2003, which exam-ined the use of rituximab in combina-tion with bendamustine (R-Bd), an

alkylating agent available for manyyears in Europe but not approved inthe United States until 2008. NHL 2-2003 compared this combi-

nation (R-Bd) with a standard regimen

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“Even with these very oldpatients [≥80 years], obtainingthe best response possibleremains crucial in terms ofoverall survival.”

—Frederic Peyrade, MD


Rituximab Effective in Several Treatment Combinationsfor Patients with LymphomaBy Neil Canavan


Non-Hodgkin Lymphoma

Research has shown little bene-fit for treating patients withfollicular lymphoma who

have not developed symptoms, buta key study at ASH 2010 found thatan early course of rituximab canhelp defer chemo therapy for nearly3 years.“Follicular lymphoma is a slow-

growing cancer that is usually wide-spread when it is diagnosed. It isgenerally considered to be incurable,and patients have an average lifeexpectancy of 10 to 12 years. Manypeople feel very well when they arefirst diagnosed and do not have anysymptoms. We know from previousstudies that there is no benefit in start-ing treatment early when patientshave no symptoms compared to wait-ing until symptoms develop,” saidKirit M. Ardeshna, MD, of UniversityCollege London Hospitals.As a result, most physicians normal-

ly defer treatment and monitorpatients closely until the disease pro-gresses, usually at around 2.5 years,although a growing number of clini-cians in the United States have alreadybegun treating patients early with rit-uximab. This new study supports thatpractice, Dr Ardeshna said.

He added that while watchful wait-ing delays the side effects of treatment,it creates anxiety in many patients.

Study DetailsThe study randomized 462 patients

into 3 treatment arms:• Watch and wait (n = 186)

• Rituximab (375 mg/m2) weekly for 4weeks (rituximab induction) (n =84). This arm was closed midwaythrough the trial because of slowrecruitment and because severalother studies were showing a bene-fit to rituximab maintenance

• Rituximab induction followed byrituximab maintenance (n = 192).The latter consisted of 1 dose of rit-uximab given every 2 months for 2years, starting at month 3 untilmonth 25.After a median follow-up of 3 years,

there was a very significant differencein the time to initiation of new thera-py between the 2 rituximab groupsand the watch-and-wait group. Only48% of patients in the watch-and-waitarm had not started chemotherapy orradiotherapy, where as 80% of patientsin the rituximab induction arm and91% of patients in the rituximabmaintenance arm were free of treat-ment. Median time to initiation ofchemo therapy was not reached at 4years, Dr Ardeshna reported at theplenary session.“Our study has shown that we can

defer chemotherapy by a long time inpatients who have asymptomatic follic-ular lymphoma,” Dr Ardeshna com-

mented. He predicted that such anapproach will prove attractive topatients, “because they can deferchemotherapy and avoid the sideeffects for a longer time. I imagine thiswill become the standard of care.”The new data come from “a very

high-quality study” and show there isa clear advantage to starting rituximabtherapy early, even before symptomsarise, said Charles Abrams, MD, of theUniversity of Pennsylvania.The study did not, however, show

an improvement in overall survival forthose receiving early rituximab thera-py. At 3 years, 96% of patients in botharms were still alive. Quality-of-lifeissues also were not addressed. These 2 factors will be examined in

future research as well as whetherpatients treated early with rituximabwill respond well to chemotherapyonce they need it, although DrArdeshna believes that early treatmentwill not compromise outcomes later on. “We are going to be following these

patients, and the study will be ongo-ing for several years. We are in this forthe long-term,” he said. �

Rituximab Effective in Several... Continued from page 13

of rituximab/fludarabine (R-F). Thepurpose of the study was a so-callednoninferiority determination betweenthe 2 therapeutic approaches, withsecondary considerations being thoseof response rate, event-free survival,overall survival, and toxicity. A total of 219 patients with a vari-

ety of lymphomas were enrolled inthe trial, with the most common con-ditions being follicular (47%), mantlecell (21%), and Waldenström’s mac -roglobulinemia (12%). The majority ofthe population started treatmentwhile already experiencing advanceddisease, and two thirds had receivedat least 1 previous treatment. Results for the R-Bd combination

were favorable compared with R-F,with an overall response rate of 82%and 49%, respectively. Complete re -sponses were observed in 39% ofpatients with R-Bd versus 16% withR-F; and the partial response rate alsoskewed toward the R-Bd combina-tion—43% versus 33%. In addition,

event-free survival was 30.4% for R-Bd and 11.2% for the standard R-Fcomparator. The most robust responsewas observed in patients with follicu-lar lymphoma.

Commenting on the observed sideeffects for R-Bd, Dr Rummel noted thatgrade 3-4 events were uncommon, andthe primary complaints were nauseaand fatigue. There were a few moreinstances of infectious complicationsin the R-Bd treatment arm, but the dif-ference was not significant, and nodose reductions were required to fulfillstudy treatment protocol.

There was no difference in overallsurvival between the 2 combinations;however, the NHL 2-2003 protocolwas amended mid-study to imple-ment the newly established paradigmof 2 years of rituximab maintenanceafter initial treatment. It is uncertainwhat effect, if any, this had on thecomparisons of eventual outcome forstudy patients.

Rituximab/BortezomibBortezomib, which is currently indi-

cated for use in multiple myeloma andadvanced mantle-cell lymphoma, wascombined with rituximab (R-Bt) in alarge, phase 3 trial that enrolled patientswith relapsed, rituximab-naïve, or rit-uximab-sensitive follicular lymphoma.Results for the R-Bt combination versusrituximab alone were reported byBertrand Coiffier, MD, PhD, of theHospices Civils de Lyon, France.The study randomized 676 patients

with advanced follicular lymphomato either rituximab alone or to the R-

Bt combination. Patients were treatedfor 25 weeks and followed for a medi-an of 33.9 months. As expected, as a result of ad -

vanced disease, discontinuation ratesin this study were high (29%); however, the response was good in lightof considerable pretreatment—63%for the combination versus 49% forrituximab alone. Differences in progression-free sur-

vival, however, were slight—12.8%for R-Bt versus 11% for rituximabalone. Significant difference wasfound in patients with the worst base-line prognosis. “This is important for me that the

patients with the higher risk toprogress still do better with the com-bination,” said Dr Coiffier. Toxicityfor R-Bt was higher than for ritux-imab alone, but symptoms were tran-sient and not life-threatening. Basedon these results, Dr Coiffier hopesthat future efficacy could be boostedwith a combination of R-Bt-CHOP. �

“Our study has shown thatwe can defer chemotherapyby a long time in patientswho have asymptomaticfollicular lymphoma….Iimagine this will become the standard of care.”

—Kirit M. Ardeshna, MD

“This is important for me thatthe patients with the higherrisk to progress still do betterwith the combination.”

—Bertrand Coiffier, MD, PhD

On January 28, 2011, the FDAapproved rituximab as a mainte-nance treatment for patients withadvanced follicular lymphoma whoresponded to initial therapy withthis drug plus chemotherapy. TheEuropean Commission approvedrituximab for this indication inOctober 2010.

Rituximab Shows Benefit inAsymptomatic Follicular LymphomaEarly Treatment Can Delay ChemotherapyBy Caroline Helwick


Based on very encouragingphase 2 trial results, the investi-gational monoclonal antibody

conjugate brentuximab vedotin seemsheaded for the marketplace for thetreatment of relapsed or refractoryHodgkin lymphoma. In a study pre-sented at the meeting, brentuximabvedotin achieved dramatic responsesin patients who have virtually notreatment options. The drug manufacturers plan to

seek regulatory approval for this prod-uct in early 2011 for the treatment ofHodgkin lymphoma and anaplasticlarge-cell lymphoma.Of the 102 patients with high-risk

refractory or relapsed Hodgkin lym-phoma, 75% achieved an objectiveresponse and 34% achieved completeremission. A majority of the patients(94%) had some degree of tumor reduc-tion, according to lead investigator,Robert Chen, MD, of City of HopeNational Medical Center, Duarte, CA.“Despite responding to front-line

combination chemotherapy, up to30% of all Hodgkin lymphomapatients will relapse. These patientshave limited treatment optionsbeyond autologous stem-cell trans-

plantation [ASCT],” Dr Chen noted. “Based on these data, brentuximab

vedotin has the potential to change thetreatment paradigm for patients withrelapsed or refractory Hodgkin lym-phoma, and could be the first treat-ment approved for these patients inmore than 20 years,” he said.

Ginna G. Laport, MD, of StanfordUniversity Medical Center, CA, com-mented on this study at ASH 2010.“This promising drug offers a newtreatment option for patients withrelapsed/refractory Hodgkin lym-phoma who have no other options.The results are very exciting, with a34% complete remission rate and 75%objective response rate. Peripheralneuropathy is an issue, but I’ve treated

several patients with this drug, and itis well tolerated,” Dr Laport said.

Study DetailsBrentuximab is an antibody drug

conjugate that targets CD30-express-ing cells, prompting apoptosis andsparing other cells from toxicity.

This phase 2 study included 102patients with relapsed/refractoryHodgkin lymphoma who had re -ceived an average of 4 previous treat-ments and had undergone ASCT. Morethan 70% had failed to achieve a com-plete remission to initial therapy or hadprogressed within 3 months, and 39%were refractory to the most recent sal-vage therapy (excluding ASCT). Patients were treated with an outpa-

tient infusion of brentuximab 1.8 mg/kgevery 3 weeks for up to 16 total doses.Progression-free survival for the

whole population was 25 weeks byindependent review and 39 weeks byinvestigator assessment, and had notbeen reached in patients who achieveda complete remission. Only 3% progressed during treat-

ment with the drug. Side effects with the investigational

drug were manageable. The most com-mon grade 3 or higher adverse eventsincluded neutropenia (20%), peripher-al sensory neuropathy (8%), thrombo-cytopenia (8%), and anemia (6%). Peripheral neuropathy occurred to

some degree in approximately 50% ofthe patients. Dr Chen acknowledgedthat this side effect is an issue withbrentuximab but noted that few casesare severe. “Overall, two thirds of theneuropathy resolved over treatment,”he said.“Brentuximab vedotin achieves

high response rates, has low toxicity,and because of these qualities, outpatient treatment allows patients tocontinue their daily routine. It hasfew side effects, and many are re -versible,” Dr Chen said. �

An escalated protocol of theBEACOPP regimen has be -come the standard of care for

the treatment of early unfavorableHodgkin lymphoma in some Germancenters, because a study showed thatit improved tumor control comparedwith standard BEACOPP. The final results of the German

Hodgkin Study Group HD14 trialwere presented by Andreas Engert,MD, of the University HospitalCologne, Germany.“We achieved overall better tumor

control with more aggressive treat-ment. The toxicity was a little higherhematologically, but this did notresult in more treatment-relateddeaths. This is now our standard ofcare,” Dr Engert said. There is currently no improvement

in overall survival, but Dr Engertnoted this may emerge with longerfollow-up. Combined modality treatment con-

sisting of 4 cycles of chemotherapy

and involved-field radiotherapy is thestandard treatment for early unfavor-able Hodgkin lymphoma. In the pre-vious HD8 study by the same investi-gators, this regimen was associatedwith a 91% rate for 5-year overall sur-vival and an 83% rate for freedomfrom treatment failure.“The rationale for HD14 was to

improve on these results by increasingthe dose intensity using BEACOPPescalated,” Dr Engert said.The study included 1655 patients

with unfavorable risk factors. Theescalated regimen included bleomycin10 mg/m2, etoposide 200 mg/m2,Adriamycin (doxorubicin) 35 mg/m2,and cyclophosphamide 1250 mg/m2,plus vincristine, procarbazine, andprednisone. Patients received 2 cyclesof escalated BEACOPP followed by2 cycles of ABVD (Adriamycin,bleomycin, vinblastine, dacarbazine),followed by radiotherapy 30 Gy IF. Thecontrol arm received 4 cycles of ABVDfollowed by the same radiotherapy.

The study included 1655 patientswho were followed a median of 42months. At 5 years, freedom from treat-ment failure (relapses and deaths) was87.6% among patients receiving stan-

dard treatment and 94.3% among thosereceiving escalated BEACOPP (P<.001). The differences were seen interms of progressive disease, earlyrelapse, and late relapse.“This absolute improvement of

about 7% met our predefined criteriafor stopping the trial and resulted in anew standard of care for us,” DrEngert said. “There were stunningdifferences in tumor control.”Dr Engert pointed out that this trial

was not only a German trial, but thatit also involved 4 European countriesand 350 centers. “This represented avery broad experience, with evensmall oncology centers taking part,”he said. Moderator of the press briefing,

Ginna G. Laport, MD, of StanfordUniversity Medical Center, said shereserves the standard BEACOPP regi-men for patients with more advanceddisease. “I can’t say I would changepractice based on this, although theresults are titillating. This is a verylarge and well-conducted trial, andalthough the toxicity is concerning,there was no difference in treatment-related mortality. If some physiciansdo switch to this regimen, I would sayit’s warranted.”—CH �

Escalated BEACOPP Prevents Treatment FailuresRegimen Now New Standard of Care in Some Centers

“Brentuximab vedotin has the potential to change the treatment paradigm forpatients with relapsed or refractory Hodgkin lymphoma, and could be the first treatment approved for these patientsin more than 20 years.” —Robert Chen, MD

Hodgkin Lymphoma

Brentuximab on the Horizon for Relapsed/RefractoryHodgkin LymphomaMay Lead to Treatment Paradigm Change By Caroline Helwick

“We achievedoverall bettertumor controlwith moreaggressivetreatment.

This is now our standard of care.” —Andreas Engert, MD

In a phase 3 trial of 502 treatment-naïve patients with CML, the investi-gational compound bosutinib failed tomeet the primary study end point—complete cytogenetic response at 1year—compared with the treatmentstandard, imatinib. Complete cytoge-netic response rates were 70% for ima-tinib versus 68% for bosutinib in theBosutinib Efficacy and Safety in Chron -ic Myeloid Leukemia (BELA) trial.A secondary end point, however,

was successful. Major molecularresponse—where cancer cells havebeen reduced but are still detected—was observed in 39% of patients treat-ed with bosutinib versus 26% receiv-ing standard therapy with imatinib. Carlo Gambacorti-Passerini, MD,

BELA lead investigator, was circum-spect about the mixed results. “We areencouraged by these data….Given thelength of time these patients are treat-ed for CML, we need more therapeu-tic options to choose from since eachpatient is different and has differentneeds,” he said. The different needs observed in the

continuum of CML treatment suggesta place for bosutinib in the third-linesetting, because this agent has previously demonstrated activity inpatients resistant or intolerant to ima-tinib. H. Jean Khoury, MD, of theEmory University School of Medicine,

presented results of a small phase 1/2study looking at the efficacy of bosu-tinib in patients who had previouslyfailed imatinib and were also resistantto dasatinib or nilotinib. In this heavily pretreated popula-

tion of 114 patients, complete cytoge-netic response ranged as high as 37%,

depending on the patient’s treatmenthistory; rates were highest for thosewho were intolerant, rather thanresistant, to imatinib, and 2-year over-all survival was also best in thisgroup. Patients resistant to imatiniband dasatinib demonstrated the leastresponse to bosutinib; however, evenin this group, for which no obvioustreatment options exist, overall sur-vival was still 66%. �

For the treatment of chronic myeloid leukemia (CML), data showingsuperior first-line efficacy continue to accrue for relative newcomers,dasatinib and nilotinib, compared with the current gold-standard treat-

ment with imatinib. Mean while, the investigational agent, bosutinib, is stilltrying to find its niche, having failed in 1 of 2 trials presented at the 2010American Society of Hematology (ASH) meeting. Making up for the lacklus-ter bosutinib showing, a phase 1 study for the newest tyrosine kinaseinhibitor, ponatinib, was impressive enough to warrant being includedamong studies highlighted at a press conference at ASH.


Leukemia

Much Progress, One Setback for CML TreatmentsBy Neil Canavan

“We are encouraged bythese data….Given thelength of time these patientsare treated for CML, we needmore therapeutic options tochoose from since eachpatient is different and hasdifferent needs.”

—Carlo Gambacorti-Passerini, MD

In the S0325 Intergroup Trial, aphase 2 study, investigators com-pared 100 mg/day of dasatinib to thestandard of 400 mg/day of imatinibin 240 newly diagnosed patients withchronic-phase CML. Results for toxicity showed that

dasatinib required more dose reduc-tions to prevent serious treatment-related complications, whereas morepatients opted to discontinue treat-ment altogether in the imatinib arm.Overall, rates for adverse events weresimilar for the 2 agents, althoughdasatinib was reported to cause moreserious cases of diarrhea, and ima-tinib, more cases of nausea.Differences in efficacy were strik-

ing. Complete cytogenetic responserate, the main indicator of efficacy inCML, was 69% for imatinib versus82% for dasatinib, and this led to farless risk of relapse with dasatinib—

0.8% versus 4.3%, respectively. Studyinvestigator Jerald P. Radich, MD,Seattle Cancer Care Alliance, WA,stated that these data “are furtherevidence that dasatinib is more effi-cacious than imatinib in the newlydiagnosed, chronic-phase CML pa -tient.” He further maintained thatthis more potent therapy may help tostave off the emergence of treatmentresistance in the long-term.

By any measure, the anticancerdrug imatinib has been a tremendoussuccess. In patients with CML, aonce-deadly disease, there is now an80% disease-free survival rate withimatinib at 8 years, yet there isalways room for improvement. “Nilotinib, as compared to ima-

tinib, is simply more potent and moreselective,” said Gianantonio Rosti,MD, lead investigator of the GruppoItaliano Malattie e Matologichedell’Adulto (GIMEMA) trial thatinvestigated front-line nilotinib. “Infact, when used in imatinib-resistantpatients, 50% are rescued with a sta-ble response.” In GIMEMA, a small phase 2 trial,

73 patients were treated with 400mg/day of nilotinib and followed formore than 3 years. This chosen timepoint is critical because this is thetime period when most treatmentfailures emerge, Dr Rosti noted. At 3, 6, and 12 months, complete

cytogenetic response rates were 78%,96%, and 100%, respectively. “Thismeans that all patients achieved acomplete cytogenetic response at

least once,” he said. At a median fol-low-up of 36 months, 99% of patientswere progression-free.

Dr Rosti admitted that GIMEMAwas a small trial, “but what is rele-vant is to show that even after 3 yearsfrom the beginning of therapy, thenumber of [treatment] failures is only1 out of 73.”

Phase 1 data for the investigationalcompound ponatinib showed intrigu-ing activity in patients with refractoryCML, according to Jorge E. Cortes,

MD, University of Texas M. D. Ander -son Cancer Center, Houston. In acohort of 55 patients who had failed 2or even 3 previous treatments, pona-tinib produced a 53% complete cyto-genetic response rate. An even more robust response was

observed for a subset of patients whoexhibited the T3151 genetic muta-tion—a genetic change that rendersall standard CML treatments ineffec-tive. An impressive “90% of patientsachieved a major cytogenetic re -sponse by 6 months,” Dr Cortes said.The cytogenetic response in theseindividuals was a remarkable 89%.“These are very exciting responses inthis patient population.” Dr Cortesnoted that these patients currentlyhave no treatment options. Some 20%to 30% of patients failing multipleagents may have the T3251mutation,he added. The encouraging resultsfor T3251 patients have led to the ini-tiation of a large multinational phase2 study.

Ponatinib Makes a Splash

Bosutinib Fails for First-Line but ShowsPromise as Third-Line Therapy

Excellent Outcomes for Nilotinib

Comparative Effectiveness: Dasatinib versus Imatinib

These data “are furtherevidence that dasatinib ismore efficacious than imatinib in the newlydiagnosed, chronic-phaseCML patient.”

—Jerald P. Radich, MD

“Nilotinib, as compared toimatinib, is simply morepotent and more selective.”

—Gianantonio Rosti, MD

An impressive “90% ofpatients achieved a majorcytogenetic response by 6 months.” —Jorge E. Cortes, MD

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Prescription drug therapy is th

e mainstay of treat-

ment for many chronic conditions, such as hyper-

tension, hyperlipidemia, diabetes, asthma, and

attention-deficit/hyperactivity disorder (ADHD). It is

well known that adherence to a prescribed drug regimen

is crucial for positive health outcomes. Medication

adherence—the extent to which patients take medica-

tion as prescribed by their healthcare provider—requires

a shared responsibility between patient and physician.1

Nonadherence is sometimes referred to as America’s

“other drug problem.”2 This widespread problem is often

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plex. One of every 4 medical visits results in

patients not

following the advice they were given.3 Each year, nonad-

herence contributes between 33% and 69% of medica-

tion-related hospital admissions.1

Studies show that within 1 year of being prescribed a

medication, patients stop taking 50% of their long-term

CLINICAL

372l American Health & Drug Benefits l www.AHDBonline.com

November/December 2010 l Vol 3, No 6

Ms Scott is Clinical Pharmacy Specialist, a

nd Ms McClure is

Medical Management Consultant, Highmark, Inc,

Pittsburgh, PA.

ORIGINAL RESEARCH

Engaging Providers in Medication

Adherence: A Health Plan Case Study

Amy B. Scott, BSPharm, RPh; Jane E. McClure, BA, RN

Background: Nonadherence to treatment regimens is a common, costly, and complex

problem that is often overlooked in a busy primary care setting.

Objective: The goals of this study were to raise providers’ awareness of nonadherence

among their patients, to identify the reasons for lack of adherence, and engage physicians

in addressing these barriers.

Method: Five primary care practices agreed to participate. The project began in the fall of

2008 with a therapy gap analysis, using prescription drug data from the previous 18 months

to identify nonadherent patients. Initially, 237 members were identified as potential nonadher-

ent patients. Each practice was presented with the data related to its patients; the group then

narrowed its sample using a chart review and/or patient outreach. Each practice had to deter-

mine the barriers to adherence, and was then asked to create action steps to improve patient

adherence based on the group’s unique results and the specific patient population.

Results: Barriers to adherence identified included prescription drug cost, multiple medica-

tions and dosing schedules, and patient as well as family level of understanding and

acceptance of disease state. Each group gained an awareness of nonadherence as it relat-

ed to their patients. For example, in the internal medicine practice, 33% (n = 17) of the

patients reported stopping their medication because of cost. A common reason for poor

adherence in the pediatric groups was that parents decided to stop their child’s medica-

tion on weekends and in the summer, without a physician’s recommendation. Using such

feedback, each practice then developed its own methods to improve medication adher-

ence within its patient population.

Conclusion: Although the final numbers in this case study were small, the providers

gained valuable insights regarding nonadherence in their practice. This study shows the

importance of engaging providers in medication adherence as a way to improve this com-

mon problem. Making this universal issue a personal problem for providers is key to over-

coming many of the adherence barriers.

Am Health Drug Benefits.

2010;3(6):372-380.

www.AHDBonline.com

Disclosures are at end of text

Jane E. McClure

Stakeholder Perspective,

page 380

“Drugs don’t work in patients who don’t take them.”1 —C. Everett Koop, MD, ScD,

former US Surgeon General

Amy B. Scott

BUSINESS

402 l American Health & Drug Benefits l www.AHDBonline.com

November/December 2010 l Vol 3, No 6

Value-Based Insurance Design: Evolving Strategies to Improve

Medication Adherence, Control Healthcare Utilization

PAYERS: Value-based health management strives

to optimize the medical benefit received for the health-

care resource purchased. It is frequently introduced to

individuals by what is now referred to as value-based

insurance design (VBID), through a member’s employ-

er or health plan. This benefit design rewards the use of

evidence-based practices through incentives such as

waived or reduced copayment/coinsurance to individu-

als for services purchased or supplemental payment to

providers for services rendered. VBID typically focuses

on benefits by a specific service (eg, cost waiver/reduc-

tion for specific drugs or services for all patients); con-

dition (eg, cost waiver/reduction for drug or service

related to a specific medical condition); condition

severity (eg, cost waiver/reduction for drugs or services

for an individual classified as high risk); or as men-

tioned in the present article by D’Souza and colleagues,

by involving “health management participation” (eg,

cost waiver/reduction for drugs or services with partici-

pation in a particular program).1

Such strategies are thought to overcome the issues

demonstrated by the increase in individuals’ cost-shar-

ing of prescription drugs through the rise in drug copay-

ments/coinsurance by means of improving drug adher-

ence and reducing potentially preventable healthcare

resource utilization (eg, emergency department visits).

Increased access to medications is an important tool

in improving care. Rates of nonadherence to asthma

medication have been reported to be as high as 70%.2

Reduced inpatient and emergency department visits

have been associated with adherence to asthma con-

troller medication.3Additional access to medication must also be tem-

pered with the opportunity for increased fraud or abuse

of the new benefits. Providers or individuals may be

encouraged to misrepresent information to benefit

from reduced copayment/coinsurance or supplemental

reimbursement for services. Expansion in fraud detec-

tion services may be necessary. Organizations will also

need to be vigilant in monitoring shifts in healthcare

resource utilization, in particular the purchase of low-

value or less clinically supported medical services,

because individuals may then have increased capacity

to purchase such services. PATIENTS: Patients will need to understand that

value-based benefit offerings, such as the H-E-B pro-

gram, are meant to optimize the quality of care they

receive. Members/patients should be encouraged to

engage in the process and take full advantage of the

opportunity presented to help improve their health.

Patients should also be on alert for potential abuse of

the process and advise their organization if they suspect

that abuse of services may have occurred. Value-based

benefit strategies that provide a “carrot” to the individ-

ual through reduced out-of-pocket expenses have not

been embraced by all organizations, but they continue

to grow in acceptance. Abuse of the system could slow

the use of such benefits and shift incentives away from

the carrot and more toward the use of the “stick” (eg,

excluded coverage, higher out-of-pocket expenses).

1. Frederick AM. Value-Based Insurance Design Landscape Digest. National

Pharmaceutical Council. July 2009. www.sph.umich.edu/vbidcenter/publications/

pdfs/NPC_VBIDreport_7-22-09.pdf. Accessed November 29, 2010.

2. Rand CS, Wise RA. Measuring adherence to asthma medication regimens. Am

J Respir Crit Care Med. 1994;149:S69-S76;discussion S77-S78.

3. Tan H, Sarawate C, Singer J, et al. Impact of asthma controller medications on

clinical, economic, and patient-reported outcomes. Mayo Clin Proc. 2009;84:675-684.

Richard F. Radzin, PharmDExecutive ConsultantCGI FederalCleveland, OH

STAKEHOLDER PERSPECTIVE

REGULATORY

Implications of the New Political Realities on Healthcare ReformInterview with Dan Mendelson

CLINICAL

Engaging Providers in Medication Adherence: A Health Plan Case StudyAmy B. Scott, BSPharm, RPh; Jane E. McClure, BA, RN

�� by F. Randy Vogenberg, PhD, RPh

BUSINESS

The H-E-B Value-Based Health Management Program: Impact on AsthmaMedication Adherence and Healthcare CostAnna O. D’Souza, PhD; Roshan Rahnama, MPH; Timothy S. Regan, BPharm, RPh; Beth Common, MBA; Steven Burch, PhD

�� by Richard F. Radzin, PharmD

� Industry Trends

� Generic Drug Trends

� AMCP Highlights

™

©2010 Engage Healthcare Communications, LLCwww.AHDBonline.com

NOVEMBER/DECEMBER 2010 VOLUME 3, NUMBER 6


FOR PAYERS, PURCHASERS, POLICYMAKERS, AND OTHER HEALTHCARE STAKEHOLDERS

��

Patients with newly diagnosedchronic myelogenous leukemia(CML) have less hospitalization

time when treated with nilotinib thanwith imatinib. “Although this difference did not

reach statistical significance, the reduc-tion in hospitalization rate is com-pelling,” said Jennifer L. Beaumont,MS, of the Department of MedicalSocial Sciences, Northwestern Uni -versity Feinberg School of Medicine,Chicago. Imatinib is the standard of care for

CML, but nilotinib is a newer, verypotent, and selective agent. A previousphase 3, open-label randomized studycomparing these 2 agents in patientswith chronic-phase CML showed thatmajor molecular responses were sig-nificantly greater with nilotinib (44%)than with imatinib (22%). Discon -tinuations because of adverse events

were also lower with nilotinib. Basedon these results, twice-daily nilotinib300 mg was approved for the treat-ment of newly diagnosed Philadelphiachromosome-positive (Ph+) chronic-phase CML. The study population included 846

patients with CML who receivedtwice-daily nilotinib 300 mg (n = 282),twice-daily nilotinib 400 mg (n = 281),or imatinib 40 mg daily (n = 283).Hospitalization was defined as a visitto the hospital requiring an overnightstay, excluding any preplanned orelective surgery. Median follow-uptime was 18.5 months.Patients were also asked to report

time off, defined as the average num-ber of hours per week taken awayfrom all usual activities as a result ofCML and treatment side effects overthe past 4 weeks, at baseline, and at theend of months 3 and 12.

There were 57 hospitalizations in theimatinib arm, 48 in the twice-dailynilotinib 300-mg arm, and 74 in thetwice-daily nilotinib 400-mg arm(Table), which resulted in a 47% high-er hospitalization rate in the imatinibarm compared with the twice-dailynilotinib 300-mg arm and 8% highercompared with the nilotinib twice-daily 400-mg arm. Patients in the nilo-tinib twice-daily 300-mg arm hadfewer hospital stays and shorter

lengths of stay than the imatinib arm.In the nilotinib twice-daily 400-mgarm, patients had more stays than withimatinib but shorter lengths of stay onaverage, resulting in fewer total hospi-tal days. The majority of hospitaliza-tions (56%) occurred within the first 9months in all arms.

“Patients in all 3 treatment groupsreported significant improvementsfrom baseline in time off from theirusual activities,” Ms Beaumont said. �

Patients with chronic myeloidleukemia (CML) receivingdasatinib were less likely to

adhere to treatment than those treat-ed with nilotinib, in a comparison ofsecond-line therapies of these tyro-sine kinase inhibitors, presented byAnnie Guerin, MSc, Senior Economistwith the Analysis Group, Boston. The study evaluated treatment

adherence associated with dasatiniband nilotinib in their approved sec-ond-line indication for patients withCML who are resistant to or intoler-ant of imatinib. Two administrative claims data-

bases were combined (MarketScanand Ingenix Impact) to identifypatients with CML who received atleast 1 treatment. Patients were fol-lowed for up to 6 months. Treatment

adherence was measured by propor-tion of days covered (PDC), whichwas calculated as the sum of thenumber of days with dasatinib ornilotinib on hand, divided by thenumber of days in the study period. The analysis included 521 patients

with CML receiving second-line ther-apy between 2003 and 2009 with nilo-tinib (n = 69) or dasatinib (n = 452). Patients in the dasatinib cohort

were significantly less adherent totheir therapy compared with pa -tients taking nilotinib. After adjust-ing for potential confounding fac-tors, patients taking dasatinib wereestimated to have a 0.096 (13%)lower PDC value, an equivalent dif-ference of 17.1 days of coverage overa 6-month period compared withnilotinib (P = .009). �


Leukemia

Table Hospitalizations and Time Off from Usual Activities: Imatinib vs Nilotinib

Hospital eventsImatinib 400

mg/dayNilotinib 300 mg

twice dailyaNilotinib 400 mg

twice dailyb

Hospitalizations, N 57 48 74

Total hospital days, N 642 434 591

Hospital days/1000patient-daysc

3.99 2.72 3.69

aP = .057 compared with imatinib.bP = .681 compared with imatinib.cTotal patient-days calculated as the sum of days from randomization to date of last contact.Adapted with permission from Beaumont J. Abstract presented at the 2010 American Society ofHematology meeting. December 6, 2010; Orlando, FL. Abstract 3826.

Comparing Patient Adherence:Nilotinib versus Dasatinib

In the largest study of its kind,investigators in the UKALL12/ECOG2993 trial demonstrated a

marked improvement in all major out-comes for patients with Philadelphiachromosome-positive (Ph+) acutelymphoblastic leukemia (ALL) byusing imatinib before therapeuticstem-cell transplantation.The UKALL12/ECOG2993 investiga-

tion had been an effort of long standing,with the first of a total of 441 patientswith Ph+ enrolled in 1993, before theavailability of imatinib. (The Ph+ genet-ic abnormality is found in several formsof leukemia and is the key indicator forsensitivity to imatinib.) The first treatment cohort, preima-

tinib, evaluated standard inductionchemotherapy before transplant withallogeneic (unrelated donor) bonemarrow stem cells.

Once imatinib became available,additional cohorts were recruited toreceive the same therapy plus ima-tinib, either concurrent with or afterinduction treatment. Patients with adequate treatment

response proceeded to transplant.

Although a number of studies havedetailed the value of imatinib in thisdisease, the size of this patient cohortand the nature of the contrasted treat-ment arms allowed for conclusions tobe made with far greater confidence,said Adele Fielding, MD, PhD, Uni -

versity Col lege London. The use of imatinib significantly

improved event-free, relapse-free,and overall survival in patients withPh+ ALL; the earlier imatinib wasused, the better the response. Theinvestigators concluded that imatinibper se did not extend survival, but itenabled greater numbers of patientsto achieve eligibility criteria for a life-saving transplantation. Commenting on the ramifications

of the study, Dr Fielding said thatalthough the use of imatinib for ALLis common in the United States, she isnot able to prescribe it in the UnitedKingdom. “It takes results from acomparative study of this size to justi-fy the expense of this drug to the offi-cials who make the final determina-tion of whether or not the treatmentwill be covered,” she noted. �

Imatinib Enhances Overall Survival in Patients with ALLBy Neil Canavan

“It takes results from acomparative study of this size to justify the expense of this drug to the officialswho make the finaldetermination of whether or not the treatment will be covered.”

—Adele Fielding, MD, PhD

Hospitalization Rates for CML Lower withNilotinib than ImatinibBy Caroline Helwick


Multiple Myeloma

In patients with newly diagnosedmultiple myeloma (MM), the use ofbortezomib before (ie, induction)

and after (ie, consolidation) autolo-gous stem-cell transplantation (ASCT)is emerging as a new standard of care.“Novel agents have shifted the

treatment paradigm for younger trans-plant-eligible patients with myeloma.Thalidomide/dexamethasone was thefirst newer induction regimen to showsuperior activity versus conventionalchemotherapy before ASCT but therate of complete response [CR] is 10%or less, which is unsatisfactory,” saidMichele Cavo, MD, Seragnoli Insti tuteof Hematology and Medical Oncology,Bologna University School of Med -icine, Italy, who spearheaded a phase 3trial. “More effective induction regi-mens are needed to increase the rate ofhigh-quality responses and improveoutcomes.” In this study, investigatorsadded bortezomib to thalidomide/dexamethasone (VTD) and maximizedthe speed of tumor reduction in prepa-ration for ASCT. “VTD consolidation led to signifi-

cantly higher rates of upgradedresponses, including complete re -sponses and molecular remissions,”Dr Cavo said. In addition, doubleASCT, incorporating VTD as inductionand consolidation therapy, resulted insignificantly longer progression-freesurvival (PFS), a benefit that wasmaintained in the subgroup withadverse cytogenetic abnormalities. The randomized study prospective-

ly compared thalidomide/dexametha-sone (TD) with VTD as induction ther-apy before, and consolidation after,double ASCT in 474 patients withnewly diagnosed MM.

Three 21-day cycles of either VTD orTD were given as induction therapy.Consolidation therapy comprised 235-day cycles of VTD or TD. The CR plus near-CR (nCR) rate was

significantly higher in the VTD armcompared with the TD arm after alltreatment phases, including induction(31% vs 11%), after the first ASCT

(52% vs 31%), after the second ASCT(55% vs 41%), and after consolidationtherapy (62% vs 45%).In a subset of patients evaluated for

the effect of the consolidation regi-mens, the bortezomib arm substan-tially improved on the preconsolida-tion responses, upgrading manyresponses from less than nCR toCR/nCR, and resulted in an absoluteCR upgrade that was twice as high asthat seen with TD.At a median follow-up of 36 months,

disease progression was reduced by39% with VTD compared with TD.Three-year PFS was 68% with VTDand 56% with TD. “The superior PFS inthe VTD arm was retained acrosspatient subgroups with poor progno-sis, including those with [chromoso-mal translocation] t(4;14) and/or[chromosome deletion] del(17p),” DrCavo added. “Random ization to VTDcompletely overcame the adverseinfluence of t(4;14), while TD plusdouble ASCT did not.” The probability of being alive at 3

years was 87% for VTD and 84% for TD.“VTD as consolidation therapy was

associated with negligible toxicity, andit significantly improved the probabil-ity of achieving CR and CR/nCR, anobjective that failed with TD consoli-dation,” Dr Cavo concluded.

Superior Induction with VTD in Spanish TrialIn the final analysis of a phase 3

study of 386 patients conducted by theSpanish Myeloma Group (PETHE-MA/GEM), induction with VTDbefore ASCT also resulted in signifi-cantly higher CR rates and significant-ly longer PFS than was achieved with2 comparative regimens. “We found that induction with VTD

resulted in a significantly higher CRrate in both the overall series and inpatients with high-risk cytogenetics,”reported Laura Rosiñol, MD, of theHospital Clinic, Barcelona, Spain. “The posttransplant CR rate was

also significantly higher with VTD,and PFS was significantly longer,”she said.Response to induction therapy was

high (35%) with VTD, and only 7% ofpatients progressed. VTD inductionwas particularly effective in patientswith extramedullary plasmacytomas,which generally are prognostic forworse outcomes. The same responsepattern held for patients with high-risk cytogenetics, with CR rates of 35%in these patients, as well.

The CR rate to VTD in patients withdel(17p) was 58%; none of thesepatients responded to other inductionregimens. Patients with t(11;14) didnot respond well to any regimen.

“Up to 50% of patients with thebortezomib-containing regimens con-tinue to respond at 2 to 4 years,” DrRosiñol noted.

Bortezomib-Based Inductionand Maintenance OvercomeChromosomal Aberrations Chromosomal aberrations are

important prognostic parameters inMM. In a large German study, newlydiagnosed patients with certain chro-mosomal alterations had worse out-comes in general (Table), but a borte-zomib-based regimen often overcamethe associated risks, especially for thet(4;14) abnormality. The study was presented by Kai Neben, MD, UniversityHospital, Heidelberg, Germany.

The study included a subgroup of833 patients within the HOVON-65/GMMG-HD 4 trial, a prospective,randomized phase 3 study in newlydiagnosed patients aged ≤65 yearswith stage II or III MM. Patients were randomized to receive

3 cycles of vincristine/Adriamycin/dexamethasone (VAD) or bortezomib/Adriamycin/dexamethasone (PAD).All patients received high-dose mel-phalan (200 mg/m²) with ASCT fol-

lowed by maintenance therapy withthalidomide (VAD group) or borte-zomib (PAD group) for up to 2 years.Investigators reported data on the first258 patients who had been followedfor an average of 40.3 months.The most pronounced impact on

prognosis was seen for t(4;14),del(17p13), and chromosome gain1q21, each significantly associatedwith poor prognosis with respect toPFS and overall survival (OS). A totalof 14.8% of patients showed t(4;14),and gain 1q21 was found in 33.7%.Bortezomib-based induction and maintenance therapy overcame the adverseoutcomes associated with severalhigh-risk aberrations. Patients with t(4;14) receiving VAD/

thalidomide had a very poor progno-sis, with a median PFS only half aslong as patients lacking the transloca-tion. But that negative effect was vir-tually ameliorated when patientsreceived PAD/bortezomib, whichresulted in approximately 40 monthsof PFS, and the 3-year OS was 76%compared with 39% for the VAD/thalidomide arm. Similarly, bortezomib significantly

prolonged OS in patients with gain1q21 but only partially overcame theadverse effect of this aberration ondisease progression. Del(17p13) wassignificantly associated with poor OSand PFS in both arms.

“Our analysis confirms the signifi-cant negative prognostic impact ofdel(17p13) and gain 1q21 on PFS andOS for patients with newly diag-nosed myeloma, but the negativeimpact of t(4;14) on PFS could almostcompletely be overcome by the borte-zomib-based treatment,” Dr Nebensaid. In contrast, the bortezomibeffect was more modest for patientswith del(17p), with a 3-year OS ofonly 62%. �

Bortezomib-Based Induction and ConsolidationEmerging as a New Standard for Multiple MyelomaBy Caroline Helwick

“VTD consolidation led tosignificantly higher rates ofupgraded responses, includingcomplete responses andmolecular remissions.”

—Michele Cavo, MD

“Up to 50% of patients withthe bortezomib-containingregimens continue torespond at 2 to 4 years.”

—Laura Rosiñol, MD

Table Prognostic Impact of Chromosomal Abnormalities on Outcome

3-year PFS 3-year OSChromosome Present, % Absent, % P Present, % Absent, % P

Del(8p21) 34 54 .005 67 83 NS

Del(13q14) 39 58 .010 73 84 .006

Del(17p13) 22 51 <.001 36 83 <.001

+1q21 22 56 .002 71 84 .010

t(4;14) 31 51 .020 55 83 <.001

NS indicates nonsignificant; OS, overall survival; PFS, progression-free survival.


AVBCC Conference

The Association for Value-BasedCancer Care’s First AnnualStakeholder Integration Conference

will be held in Philadelphia on March 29-30, 2011 (see full agenda below). To helpset the stage for this meeting, Value-Based Cancer Care (VBCC) interviewedGary Owens, MD, one of the cochairs ofthe meeting. Dr Owens is president ofGary Owens Associates, a medical man-agement and pharmaceutical consultingfirm in the Philadelphia area. Dr Owensis a primary care physician who has spent20 years in health plans, and one of hismajor areas of focus during that time hasbeen oncology.

VBCC: Why this meeting now?Gary Owens, MD: A number of rea-

sons, the first being the obvious rapidgrowth of spending that the playersin the oncology world—including thefederal government, health plans,and the public—is seeing. As PeterBach noted several years ago in theNew England Journal of Medicine(2009;360:626-633), the cost of cancercare agents has risen dramaticallyover the years, and the ability to con-trol those costs has been limited. Babyboomers are aging, and people areliving longer with cancer. It is analmost-perfect storm (see Sidebar).Ultimately, the goal is to provide the

best care possible for patients withmalignant disorders but to spendthose care resources wisely. We don’twant to withhold treatment from thosewho need it, but we don’t want towaste treatment in those for whom it isineffective or unproven. This meetingwill examine all these topics.

VBCC: Who will be presenting atthis meeting, and what topics canwe expect to be covered?

Dr Owens: We have some keythought leaders. On the clinical side, AlBenson, MD, the current president ofthe Association of Community CancerCenters, and A. Mark Fendrick, MD,from the University of Michigan, willboth present. Dr Fendrick is a drivingforce behind the value-based benefitmovement, and it will be interesting tohear his perspective.Along the lines of targeted therapy,

we have a session on the age of per-sonalized oncology therapy thatpromises to be a very cogent topic.Right now, these offer more promisethan reality. Although there are a fewsuccessful examples of this so far—KRAS testing and colorectal cancer,HER2/neu testing and breast cancer,and ABR-BCL mutations in chronicmyelogenous leukemia—this is anarea that will continue to grow, so itwas essential that we cover this.

In the future, I suspect that drugswill come to market with companiondiagnostics attached to them. I’m notsure that health plans, providers, oranyone else is tuned in as to how tomanage these situations effectively. Other areas to be covered will

include clinical treatment of cancerpatients, the use of guidelines, andpatient navigators and patient-assis-tance programs. With the growingnumber of uninsured and underin-sured patients, we can’t forget aboutthe difficulties these individuals face

in accessing treatment, so these lattersessions will be important.

VBCC: What’s different about this meeting?

Dr Owens: A big plus is that itbrings together different viewpoints

Tuesday, March 291:30 – 3:30 pm PAYER PRE-CONFERENCE (Off-site)Ritz-Carlton Philadelphia10 Avenue of the Arts, Philadelphia, PA 19102

Payer Trends in Oncology - Panel DiscussionMODERATORBurt Zweigenhaft, BSPANELScott Breidbart, MD — CMO, Empire BCBSNick J. Calla, RPh — VP, Trade Relations, Walgreens Specialty PharmacyMaria Lopes, MD — CMO, AMC HealthMona Chitre, PharmD — Director, Clinical Strategy, Policy, and Services, Excellus

�� GENERAL PRE-CONFERENCE SESSIONSLoews Philadelphia Hotel 1200 Market Street, Philadelphia, PA 19107-3615

Value-Based Insurance Design in OncologyCHAIRA. Mark Fendrick, MD – Co-Director, University of Michigan Center forValue-Based Insurance DesignCancer Care from a Large Insurer’s PerspectiveDonald Liss, MD – Senior Medical Director, Independence Blue Crossof PhiladelphiaThe Role of Diagnostics from a PBM’s StandpointJane F. Barlow, MD, MPH, MBA – VP, Clinical Innovation, MEDCO Health SolutionsPanel Discussion

�� Welcome/Networking Reception

Wednesday, March 30�� Corporate-Sponsored Breakfast Symposium

Havalen™ (eribulin mesylate) Injection:A New FDA-approved Treatment Funded by Eisai Inc.

Stephen C. Malamud, MD –Beth Israel Medical Center

�� Intro/Opening

�� NCCN Guidelines Acceptance and ComplianceAl Benson, MD – President, ACCC

�� The Impact of Personalized Oncology TherapiesMODERATORGary Owens, MDPANELPerry Dimas – VP, Premier Source DiagnosticsRichard Bender, MD – CMO, AgendiaBeth Davis – Senior Director, Managed Care, AgendiaGene Morse, PharmD – University of Buffalo

�� Morning Break in the Exhibit Hall

�� BREAKOUT SESSIONS

PROVIDER TRACKCommunity Oncology: TrendsTed Okon – Executive Director, Community Oncology AlliancePatient Navigation/Patient AssistanceSteven Patierno, PhD – Executive Director, George Washington University Cancer InstituteDawn Holcombe, MBA, FACMPE, ACHE – President, DGH ConsultingMonica Knoll – Executive Director/Founder, CANCER101

Oncology Practices—Issues with Managed CareCraig Deligdish, MD – Medical Director, Florida Comprehensive Care NetworkYu-Ning Wong, MD – Fox Chase Cancer CenterWinston Wong, PharmD – Associate VP, Pharmacy Management, CareFirst BCBS

PAYER TRACKMedicare and Reimbursement IssuesKip Piper, MA, FACHE – President, Health Results GroupJayson Slotnik, JD – Counsel, Foley HoagOncology Drug Reimbursement and Administration IssuesJohn Aforismo, BSc Pharm, RPh, FASCP – President & CEO, RJ Health SystemsPeyton Howell, MBA – AmerisourceBergenScott Breidbart, MD – CMO, Empire BCBSEvolutions in Oncology Pharmacy ManagementMODERATORBurt Zweigenhaft, BSROUNDTABLEAlan Lotvin, MD – President, ICOREKristen M. Reimers, RPh – Clinical Pharmacy Operations Manager, ExcellusJeff Ulanet – VP, Oncology, MEDCO

�� LUNCH SYMPOSIUMBest Practices for Management of CINV: A Value-Based ApproachSupported by an educational grant from Eisai Inc.

Shawna Kraft, PharmD, BCOP – Hematology/Oncology Clinical Pharmacist, University of Michigan Health SystemBeth Faiman, RN, MSN, CNP, AOCN – Nurse Practioner,Cleveland Clinic Taussig Cancer Center

�� Cancer Care and the New Healthcare Legislation: What to Expect NextMODERATORJayson Slotnik, JDPANELScott Gottlieb, MD – Resident Fellow, American Enterprise InstituteJoseph Bailes, MD – Texas Oncology

�� Strategies for Improving Oncology Pharmacy and Care Management ModelsMODERATORBurt Zweigenhaft, BSPANELIra M. Klein, MD – Medical Director, Aetna Oncology StrategyDan McCrone, MD – CMO, New Century HealthJeffery Scott, MD – SVP/CMO, P4 Healthcare, Cardinal HealthWinston Wong, PharmD

�� Afternoon Break in the Exhibit Hall

�� Clinical Fragmentation: Impact of Oral, Injected,and Infused TherapiesMODERATORGary Owens, MDROUNDTABLEAtheer Kaddis, RPh – VP, Managed Markets, Diplomat Pharmacy ServicesKirby Eng, RPh – Director, Oncology Management Services, CVS CaremarkEllen Scharaga, BS – SVP, Pharmacy Operations, OncoMed

�� Cocktails/Networking in the Exhibit Hall

First Annual Stakeholder Integration Conference Integrating Payers, Providers, and the Entire Oncology Team

March 29-30, 2011Philadelphia, PA

Loews Philadelphia Hotel

��

PROGRAM OVERVIEWThis is the first national stakeholder integration meeting dedicated toadvancing the understanding of value in cancer care. Guided by theexpertise of leaders in these fields, attendees will receive a thoroughunderstanding of the evolution of the value equation as it relates tocancer therapies and will be able to implement, improve, and sustaintheir companies and institutions, while improving access for patientsand ultimately patient care.

WHO SHOULD ATTENDAll stakeholders in a position to impact cancer patient care are in-vited to join this exciting forum. Specifically this conference is in-tended for:•Medical Oncologists •Advanced Practitioners•Hematologists/Oncologists •Managed Care Professionals•Surgical Oncologists •Medical Directors•Nurses • Practice Managers/Administrators•Pharmacists • Pharmacy Benefit Managers (PBMs)

CONTINUING EDUCATION INFORMATIONGoalThe Association for Value-Based Cancer Care’s First Annual Stake-holder Integration Conference will foster an open dialogue betweenproviders, payers, and/or other members of the oncology team inorder for attendees to gain a better understanding of various pointsof view regarding cost, quality, and access in cancer care.Objectives• Examine the impact of healthcare reform on all stakeholders in-volved in the management of patients with cancer

• Identify issues and potential solutions to challenges with accessand affordability of oncology therapeutics

• Determine the value equation of cost, quality, and access whenevaluating the diagnosis, treatment, and overall management ofcancer patients

• Define appropriate comparative effectiveness research and clini-cal pathways as tools to evaluate current recommendations forpatient management

• Analyze trends in the delivery of care in the management ofcancer patients

PRIMARY CONFERENCE LOCATIONLoews Philadelphia Hotel 1200 Market Street, Philadelphia, PA 19107-3615Phone: 215-627-1200 http://www.loewshotels.com/en/Philadelphia-Hotel

ACCREDITATION INFORMATIONPHYSICIAN ACCREDITATIONScience Care designates this activity for a maximum of 6.0 AMAPRA Category 1 Credit(s)™. Science Care is accredited by the Ac-creditation Council for Continuing Medical Education (ACCME)to provide continuing medical education for physicians. Physiciansshould only claim credit commensurate with the extent of their par-ticipation in the activity.

REGISTERED NURSE DESIGNATIONMedical Learning Institute, Inc. (MLI)Provider approved by the California Board of Registered Nursing, Provider Number 15106, for 6.0 contact hours.

REGISTERED PHARMACY DESIGNATIONMedical Learning Institute is accredited by the AccreditationCouncil for Pharmacy Education (ACPE) as a provider ofcontinuing pharmacy education. Completion of this activity

provides for 7.50 contact hours (0.750 CEUs) of continuing educa-tion credit.

The Universal Activity Number for General Sessions is: 0468-9999-11-072-L01-P.

The Universal Activity Number for the lunch symposium is: 0468-9999-11-071-L01-P.

CONFERENCE REGISTRATIONRegister Online at

www.regonline.com/avbcc-2011$250 Includes 1-year association membership$355 Includes 3-year association membership

CONTACT/SUPPORTIf you have any questions please contact:

Association for Value-Based Cancer Care™241 Forsgate Drive, Suite 205B, Monroe Township, NJ 08831

Phone: 732-992-1040 [email protected]

REGISTER ONLINE ATwww.regonline.com/avbcc-2011

��

Gary Owens, MD President, Gary Owens Associates

Burt Zweigenhaft, BSPresident, CEO, OncoMed

Co-Chairs

��

Conference Promises Valuable Perspectives


AVBCC Conference

from various stakeholders, includinghealth plans, pharmacy benefit man-agers, providers, patients, govern-ment, manufacturers, and theNational Com pre hensive CancerNetwork. We’re attempting to bringtogether a group that owns different

pieces of the cancer care equation,and to hear about the world of oncol-ogy through their eyes. We hope toidentify common issues and under-stand how we might integrate these. The current situation with Avastin

provides an excellent example of the

interconnected nature of cancer caretoday. The US Food and Drug Admin -istration (FDA)’s accelerated approvalwas based on the requirement of fur-ther data on patients with metastaticbreast cancer. Compendia, however,continue to advocate coverage for this

condition as do some patient groups.So we have a situation where the FDAis taking one action and the realworld another. Some patients are ben-efiting but many are probably not.Con ferences such as these can behelpful in shedding light on the issuesbehind these situations. We’re trying to open up the lines of

communication between these vari-ous groups. Currently, stakeholdersmay not have a chance to “cross-pol-linate,” as we’re hoping to do here. Imay have seen only 1 or 2 other meet-ings that have even tried to bringtogether this many stakeholders. Wetend to live in our own world andoften only see our own points of view,so it can be eye-opening to see thoseother viewpoints.We will feature multiple presenters,

with interactivity not only amongpresenters but with members of theaudience. We believe that this audi-ence is going to have as much expert-ise as the people behind the podium,which should make for excellentinteractions. �

Tuesday, March 291:30 – 3:30 pm PAYER PRE-CONFERENCE (Off-site)Ritz-Carlton Philadelphia10 Avenue of the Arts, Philadelphia, PA 19102

Payer Trends in Oncology - Panel DiscussionMODERATORBurt Zweigenhaft, BSPANELScott Breidbart, MD — CMO, Empire BCBSNick J. Calla, RPh — VP, Trade Relations, Walgreens Specialty PharmacyMaria Lopes, MD — CMO, AMC HealthMona Chitre, PharmD — Director, Clinical Strategy, Policy, and Services, Excellus

�� GENERAL PRE-CONFERENCE SESSIONSLoews Philadelphia Hotel 1200 Market Street, Philadelphia, PA 19107-3615

Value-Based Insurance Design in OncologyCHAIRA. Mark Fendrick, MD – Co-Director, University of Michigan Center forValue-Based Insurance DesignCancer Care from a Large Insurer’s PerspectiveDonald Liss, MD – Senior Medical Director, Independence Blue Crossof PhiladelphiaThe Role of Diagnostics from a PBM’s StandpointJane F. Barlow, MD, MPH, MBA – VP, Clinical Innovation, MEDCO Health SolutionsPanel Discussion

�� Welcome/Networking Reception

Wednesday, March 30�� Corporate-Sponsored Breakfast Symposium

Havalen™ (eribulin mesylate) Injection:A New FDA-approved Treatment Funded by Eisai Inc.

Stephen C. Malamud, MD –Beth Israel Medical Center

�� Intro/Opening

�� NCCN Guidelines Acceptance and ComplianceAl Benson, MD – President, ACCC

�� The Impact of Personalized Oncology TherapiesMODERATORGary Owens, MDPANELPerry Dimas – VP, Premier Source DiagnosticsRichard Bender, MD – CMO, AgendiaBeth Davis – Senior Director, Managed Care, AgendiaGene Morse, PharmD – University of Buffalo

�� Morning Break in the Exhibit Hall

�� BREAKOUT SESSIONS

PPRROOVVIIDDEERR TTRRAACCKKCommunity Oncology: TrendsTed Okon – Executive Director, Community Oncology AlliancePatient Navigation/Patient AssistanceSteven Patierno, PhD – Executive Director, George Washington University Cancer InstituteDawn Holcombe, MBA, FACMPE, ACHE – President, DGH ConsultingMonica Knoll – Executive Director/Founder, CANCER101

Oncology Practices—Issues with Managed CareCraig Deligdish, MD – Medical Director, Florida Comprehensive Care NetworkYu-Ning Wong, MD – Fox Chase Cancer CenterWinston Wong, PharmD – Associate VP, Pharmacy Management, CareFirst BCBS

PPAAYYEERR TTRRAACCKKMedicare and Reimbursement IssuesKip Piper, MA, FACHE – President, Health Results GroupJayson Slotnik, JD – Counsel, Foley HoagOncology Drug Reimbursement and Administration IssuesJohn Aforismo, BSc Pharm, RPh, FASCP – President & CEO, RJ Health SystemsPeyton Howell, MBA – AmerisourceBergenScott Breidbart, MD – CMO, Empire BCBSEvolutions in Oncology Pharmacy ManagementMODERATORBurt Zweigenhaft, BSROUNDTABLEAlan Lotvin, MD – President, ICOREKristen M. Reimers, RPh – Clinical Pharmacy Operations Manager, ExcellusJeff Ulanet – VP, Oncology, MEDCO

�� LUNCH SYMPOSIUMBest Practices for Management of CINV: A Value-Based ApproachSupported by an educational grant from Eisai Inc.

Shawna Kraft, PharmD, BCOP – Hematology/Oncology Clinical Pharmacist, University of Michigan Health SystemBeth Faiman, RN, MSN, CNP, AOCN – Nurse Practioner,Cleveland Clinic Taussig Cancer Center

�� Cancer Care and the New Healthcare Legislation: What to Expect NextMODERATORJayson Slotnik, JDPANELScott Gottlieb, MD – Resident Fellow, American Enterprise InstituteJoseph Bailes, MD – Texas Oncology

�� Strategies for Improving Oncology Pharmacy and Care Management ModelsMODERATORBurt Zweigenhaft, BSPANELIra M. Klein, MD – Medical Director, Aetna Oncology StrategyDan McCrone, MD – CMO, New Century HealthJeffery Scott, MD – SVP/CMO, P4 Healthcare, Cardinal HealthWinston Wong, PharmD

�� Afternoon Break in the Exhibit Hall

�� Clinical Fragmentation: Impact of Oral, Injected,and Infused TherapiesMODERATORGary Owens, MDROUNDTABLEAtheer Kaddis, RPh – VP, Managed Markets, Diplomat Pharmacy ServicesKirby Eng, RPh – Director, Oncology Management Services, CVS CaremarkEllen Scharaga, BS – SVP, Pharmacy Operations, OncoMed

�� Cocktails/Networking in the Exhibit Hall

First Annual Stakeholder Integration Conference Integrating Payers, Providers, and the Entire Oncology Team

March 29-30, 2011Philadelphia, PA

Loews Philadelphia Hotel

��

PROGRAM OVERVIEWThis is the first national stakeholder integration meeting dedicated toadvancing the understanding of value in cancer care. Guided by theexpertise of leaders in these fields, attendees will receive a thoroughunderstanding of the evolution of the value equation as it relates tocancer therapies and will be able to implement, improve, and sustaintheir companies and institutions, while improving access for patientsand ultimately patient care.

WHO SHOULD ATTENDAll stakeholders in a position to impact cancer patient care are in-vited to join this exciting forum. Specifically this conference is in-tended for:•Medical Oncologists •Advanced Practitioners•Hematologists/Oncologists •Managed Care Professionals•Surgical Oncologists •Medical Directors•Nurses • Practice Managers/Administrators•Pharmacists • Pharmacy Benefit Managers (PBMs)

CONTINUING EDUCATION INFORMATIONGoalThe Association for Value-Based Cancer Care’s First Annual Stake-holder Integration Conference will foster an open dialogue betweenproviders, payers, and/or other members of the oncology team inorder for attendees to gain a better understanding of various pointsof view regarding cost, quality, and access in cancer care.Objectives• Examine the impact of healthcare reform on all stakeholders in-volved in the management of patients with cancer

• Identify issues and potential solutions to challenges with accessand affordability of oncology therapeutics

• Determine the value equation of cost, quality, and access whenevaluating the diagnosis, treatment, and overall management ofcancer patients

• Define appropriate comparative effectiveness research and clini-cal pathways as tools to evaluate current recommendations forpatient management

• Analyze trends in the delivery of care in the management ofcancer patients

PRIMARY CONFERENCE LOCATIONLoews Philadelphia Hotel 1200 Market Street, Philadelphia, PA 19107-3615Phone: 215-627-1200 http://www.loewshotels.com/en/Philadelphia-Hotel

ACCREDITATION INFORMATIONPHYSICIAN ACCREDITATIONScience Care designates this activity for a maximum of 6.0 AMAPRA Category 1 Credit(s)™. Science Care is accredited by the Ac-creditation Council for Continuing Medical Education (ACCME)to provide continuing medical education for physicians. Physiciansshould only claim credit commensurate with the extent of their par-ticipation in the activity.

REGISTERED NURSE DESIGNATIONMedical Learning Institute, Inc. (MLI)Provider approved by the California Board of Registered Nursing, Provider Number 15106, for 6.0 contact hours.

REGISTERED PHARMACY DESIGNATIONMedical Learning Institute is accredited by the AccreditationCouncil for Pharmacy Education (ACPE) as a provider ofcontinuing pharmacy education. Completion of this activity

provides for 7.50 contact hours (0.750 CEUs) of continuing educa-tion credit.

The Universal Activity Number for General Sessions is: 0468-9999-11-072-L01-P.

The Universal Activity Number for the lunch symposium is: 0468-9999-11-071-L01-P.

CONFERENCE REGISTRATIONRegister Online at

www.regonline.com/avbcc-2011$250 Includes 1-year association membership$355 Includes 3-year association membership

CONTACT/SUPPORTIf you have any questions please contact:

Association for Value-Based Cancer Care™241 Forsgate Drive, Suite 205B, Monroe Township, NJ 08831

Phone: 732-992-1040 [email protected]

REGISTER ONLINE ATwww.regonline.com/avbcc-2011

��

Gary Owens, MD President, Gary Owens Associates

Burt Zweigenhaft, BSPresident, CEO, OncoMed

Co-Chairs

��

Cancer Costs Projection:Population Booming,Costs Zooming

The estimated total cost of can-cer care in the United States is pro-jected to be $158 billion by 2020 ifcurrent patterns of incidence, sur-vival, and cost remain the same. Ifcare costs increase 2% in the initialand last phases of treatment abovethe base estimates, however, totalcosts of care could reach $173 bil-lion by 2020, an increase of 39%from 2010.This analysis appears in the

Journal of the National CancerInstitute (Mariotto AB, et al. 2011;103:117-128). By 2020, the authors estimate

there will be 18.1 million cancersurvivors in the United States,whose care will cost $157.7 billion,a 27% increase from 2010’s amountof $124.5 billion.Despite this profound possible

increase, the authors are hopeful.“Expanding costs of cancer caredue to increases in an aging popu-lation are inevitable,” they note,“but the costs of new treatmentsand diagnostic technologies couldpotentially be managed to ensureaccess to quality care for allpatients.”

Patients with newly diagnosedor previously treated multiplemyeloma (MM) administered

thalidomide- or lenalidomide-basedregimens are at high risk for venousthromboembolism (VTE), but thenecessity of thromboprophylaxis andthe choice of agent are not clear. Recent observational studies have

suggested that thromboprophylaxismay be efficacious in decreasing risk,and consensus guidelines recom-mend routine thromboprophylaxis,but reliable data from randomized,controlled trials are lacking. Twostudies at ASH provided some infor-mation on this issue. In a meta-analysis by Canadian

investigators, clear benefit for thrombo-prophylaxis was not found, especiallyfor patients receiving lenalidomide andfor previously treated patients, whoserisk appears low. Marc Carrier, MD, MSc, FRCPC,

Division of Hematology, University ofOttawa, Ontario, Canada, and col-leagues investigated the ab solute ratesof VTE with/without throm boprophy-lactic agents—aspirin, warfarin, low-

molecular-weight heparin (LMWH)—in patients with newly diagnosed orpreviously treated MM. Their systematic literature review

included 66 studies: 61 studies (with4264 pa tients) evaluated thalidomide-based regimens, and 5 studies (involv-ing 1119 pa tients) assessed lenalido-mide-based strategies.

Thalidomide-Based RegimensFor the 444 newly diagnosed

patients with MM who were treatedwith thalidomide only, the rates ofVTE (per 100 patient-cycles) were 1.3for the patients (n = 380) who did notreceive VTE prophylaxis and 0.5 for

those receiving LMWH prophylaxis. For newly diagnosed patients who

received the combination of thalido-mide plus dexamethasone, the rates ofVTE (per 100 patient-cycles) were:• 4.1 (n = 628) without prophylaxis• 2.3 (n = 80) with aspirin• 2.8 (n = 87) with warfarin• 2.1 (n = 446) with LMWH.The rates of VTE (per 100 patient-

months) in patients with previouslytreated MM managed with thalido-mide-based regimens who did notreceive prophylaxis VTE were: • 0.4 (n = 706) with thalidomide alone• 0.6 (n = 258) with thalidomide plusprednisone

• 0.4 (n = 38) with thalidomide pluschemotherapy

• 0.9 (n = 321) with thalidomide plusdexamethasone plus chemotherapy

• 6.7 (n = 331) with thalidomide plusdexamethasone plus chemothera-py, including doxorubicin.

Lenalidomide-Based RegimensThe rates of VTE (per 100 patient-

cycles) in patients with newly diag-nosed MM treated with lenalidomide

and dexamethasone were:• Any prophylaxis: 0.7 (n = 349)• Aspirin: 0.9 (n = 172)• No prophylaxis: 0.8 (n = 278).The rates of VTE (per 100 patient-

months) in patients with previouslytreated MM managed with lenalido-mide-based regimens were: • No prophylaxis: lenalidomide +dexamethasone, 0.7 (n = 361)

• Aspirin: lenalidomide + dexameth a-sone + chemotherapy, includingdoxorubicin, 0.6 (n = 131).None of the studies reported major

bleeding events. Of note, the defini-tion for VTE varied across studiesand/or was unclear, and data are notavailable for all prophylaxis regimens.

Low Thromboembolism Rates withEither AgentAn Italian study evaluated newly

diagnosed patients with MM receivinglenalidomide and dexamethasone andshowed the overall incidence ofthrombotic events to be less than 5% inall groups, “confirming the safety oflow-dose dexamethasone in associa-tion with lenalidomide,” according to


Multiple Myeloma

Advances in treatment havehelped to achieve levels ofresponse and durations of

remission in multiple myeloma (MM)that were previously not achievablewith standard approaches. As a result,patients with MM are living signifi-cantly longer than a decade ago. Drugsthat have made such a differenceinclude thalidomide, bortezomib, andlenalidomide, which are used in vari-ous combinations together and withother conventional agents, such asdexamethasone. Now, next-generation agents are in

development, and new targets arebeing refined. Sagar Lonial, MD, Direc -tor of the Translational Research B-cellMalignancy Program, Hematology andMedical Oncology, Winship CancerInstitute, Emory University School ofMedicine, discussed the current ap -proach to remission in MM. Remissions are becoming longer,

although eventually all patients withMM relapse. Patients with remissiondurations of <6 months and those withsigns of aggressive relapse are differ-ent from patients with indolent, slow-ly progressing disease. The physician

must consider which agents thepatient has been given and the dura-tion of response to each. Some patientsare good candidates for single-agentapproaches and some need combina-tion treatment. In addition, patientswith a high-risk cytogenetic featureusually warrant combinations, DrLonial said. For relapse, allogeneic transplant

“remains a strategy with limited clin-ical benefit,” according to Dr Lonial,“since long-term disease-free survivalis seen in only 10% to 20% of patients,with a significant fraction developingdebilitating chronic graft-versus-hostdisease or relapse. The use of alloge -neic transplant for managing relapsedmyeloma should be discouraged.”

Second-Generation Agents andNew Versions of Active AgentsA promising investigative approach

is to combine the proteasome inhibitorbortezomib with agents targeting newpathways (Table).

These include heat shock proteininhibitors (eg, 17AAG), histonedeacetylase inhibitors (eg, vorinostat,panobinostat), and drugs that targetthe PI2K/AKT/mTOR pathways (eg,perifosine), which appear to be acti-vated after exposure to bortezomib. A number of novel approaches

made news at ASH 2010. Especiallypromising was the monoclonal anti-body elotuzumab, which looks activein combination with the immuno -modulatory agent lenalidomide. Highresponses were also seen with carfil-zomib, a second-generation proteasomeinhibitor, and with pomalidomide, anew im mun o modulatory agent.“It is clear that the availability of

new classes of agents and new protea-some inhibitors and immunomodula-tory agents have changed the naturalhistory of MM over the past 10 years,”Dr Lonial said. “Their use both in theinduction setting and relapsed diseasesetting, either alone or in combina-tions, has resulted in significantimprovements in overall survival. Thewealth of second-generation andnewer agents currently suggests thatthis improvement will continue.” �

“The wealth of second-generation and newer agentscurrently suggests that thisimprovement will continue.”

—Sagar Lonial, MD Table New Agents in Phase 3 Trials

Bortezomib ± vorinostat (HDACinhibitor)

Bortezomib/dexamethasone ± perifosine (AKT inhibitor)

Bortezomib/dexamethasone ± panobinostat (HDAC inhibitor)

Lenalidomide/dexamethasone ± carfilzomibHDAC indicates histone deacetylase.

Advances in Multiple Myeloma Likely to Expandwith Current Drugs in Development By Caroline Helwick


Is Thromboprophylaxis Necessary in Patients withMultiple Myeloma?

“LMWH and aspirin arelikely to be effectivethromboprophylacticregimens in lenalidomide-treated patients with newlydiagnosed myeloma.”

—Federica Cavallo, PhD

According to 2 studies present-ed at ASH 2010, the use ofzoledronic acid (ZA) in

patients with multiple myeloma(MM) to prevent bone complicationswas superior to some, but not all, bis-phosphonates in improving overallsurvival (OS), and the drug was cost-effective compared with clodronate.In the meta-analysis, ZA had a ben-

eficial effect on OS compared with clo-dronate, and etidronate was superiorto clodronate in improving progres-sion-free survival (PFS). In preventingskeletal-related events (SREs), ZA wassuperior to clodronate, pamidronate,ibandronate, reported Rahul Mhaskar,MD, MPH, Center for Evidence-BasedMedicine and Health Out comes Re -

search, at the H. Lee Moffitt CancerCenter, Tampa, FL. “In the context of a mixed treatment

comparison uncertainty analysis, ZAranked as the best treatment, followed

by clodronate and pamidronate,” DrMhaskar said. The analysis was basedon 18 randomized controlled trials thatenrolled 4970 patients. Superiority ofbisphosphonates was assessed by the

mixed treatment comparison. The pooled analysis demonstrated

an OS benefit with ZA comparedwith clodronate and etidronate, butthere was no evidence that zole-


Multiple Myeloma

Mark B. McClellan, MD, PhDDirector, Engelberg Centerfor Health Care ReformBrookings Institution

Mark T. BertoliniChief Executive Officerand PresidentAetna

George C. Halvorson,Chairman and Chief ExecutiveOfficer, Kaiser PermanenteBoard of Directors, AHIP

Len M. Nichols, PhDDirector, Center for Health PolicyResearch and Ethics; Professorof Health PolicyGeorge Mason University

Joseph JimenezChief Executive OfficerNovartis

Bertram L. ScottPresidentU.S. CommercialCIGNA Corporation

Joseph F. Coughlin, PhDFounder and DirectorMassachusetts Instituteof Technology AgeLab

William A. HawkinsChairman andChief Executive OfficeMedtronic

Charles W. Sorenson, Jr, MDPresident andChief Executive OfficerIntermountain Health Care

Meg McCarthyChief Information Officer, Senior VicePresident of Innovation Technologyand Service Operations Aetna, Inc.

Zoë BairdPresidentMarkle Foundation

David J. Brailer, MD, PhDFounder, Health EvolutionPartners; Former and First NationalCoordinator for Health InformationTechnology, U.S. Department ofHealth and Human Services

Jonathan B. Perlin, MD, PhDPresident, Clinical Servicesand Chief Medical OfficerHCA, Inc. / HospitalCorporation of America

Bruce J. GoodmanSenior Vice President, Chief Serviceand Information OfficerHumana

His Excellency Hatem El-GabaliMinister of Health and PopulationMinistry of Health and Population(Egypt)

The Cost Crisis in Health Care

Leveraging Information and Technology to Drive Efficiencies

Bart Asner, MDChief Executive OfficerMonarch HealthCare

Alfred B. Knight, MDChief Executive OfficerScott & White MemorialHospital/Foundation andScott & White Health Plan

The 8thAnnual

Driving Post-Reform Innovation and Collaboration to Achieve Quality, Cost-Effective Care

Educational Underwriters:

Official Public Relations Partner:

Official Innovation Series Sponsor:

Official Healthcare Decisions Sponsor:

Official Well-Being Sponsor:

Presidential Sponsor:

Adapting International Best Practices

JustConfirmed!

Dr. Zakiuddin AhmedNational Coordinator of Telemedicine andeHealth Ministry of Health (Pakistan) FocalPerson for Health,World Health OrganizationChief Executive Officer, eHealth Service Pvt. Ltd

Hisham Diwani,MDGeneral Manager, Health InsuranceMinistry of Health of Syria;Member,Syrian InsuranceSupervisory Commission (Syria)

Featuring the 2nd Annual World Health Innovation Summit!

Susan E. VossPresident, National Association ofInsurance Commissioners (NAIC)Commissioner, Iowa InsuranceDivision

WHAT TO EXPECT AT THE 8TH ANNUAL WORLD HEALTH CARE CONGRESSThe Next Stages of Health Reform —Through 13 keynote sessions, 10 executive summits, 10 emerging trend forums, 10innovation andmarket insight series - WHCC featuresmulti-perspective, high-level panel discussions that deliver expertopinions on the necessities to drive efficiency and quality in care—and the possibility of dismantling health reform

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April 4-6, 2011 • Gaylord National Resort and Convention Center • Washington, DC

Max BaucusUnited States SenatorChairmanUnited States SenateFinance Committee

Innovation for the Health Care ConsumerRobert Blendon, ScDSenior Associate Dean, Policy Translationand Leadership Development; Professorof Health Policy and Political AnalysisDepartment of Health andPolicyManagementHarvard School of Public Health

Official Publication:

Federica Cavallo, PhD, AssociateProfessor of Immunology, Universityof Torino, Italy. Preliminary studies of patients

with MM receiving lenalidomide plusdexamethasone had shown an oddsratio of about 3.5 for the developmentof thrombosis. In a comparison of agents, no sig-

nificant benefit was seen for LMWHover aspirin in this patient popula-tion. “LMWH and aspirin are likely tobe effective thromboprophylacticregimens in lenalidomide-treatedpatients with newly diagnosed mye -loma,” she said. The data came from a substudy of a

prospective, multicenter phase 3 trialof 402 newly diagnosed patients withMM treated with lenalidomide andlow-dose dexamethasone inductionand subsequently randomized to con-solidation with lenalidomide plus mel-phalan and prednisone or high-dosemelphalan. Patients were randomlyassigned to receive LMWH or aspirinduring induction therapy and consoli-dation therapy. During induction, the overall inci-

dence of grade 3 to grade 4 thromboticevents was 1% in the LMWH groupand 2.4% in the aspirin group. VTEs,mostly of the lower limbs, were equal-ly distributed in the 2 groups, whereaspulmonary embolism was observedonly in the aspirin group. Only minor bleeding was detected

in the LMWH group (1%), and nothrombotic events were observed dur-ing consolidation.—CH �

Is Thromboprophylaxis...Continued from page 22


Cost-Effectiveness Analysis: Zoledronic Acidversus ClodronateBy Caroline Helwick


Multiple Myeloma

Young patients with multiplemyeloma (MM) often receivehigh-dose therapy with autolo-

gous stem-cell transplantation (ASCT).Residual disease in evitably leads torelapse, and a research aim has been todetermine ways to prevent this. In 2phase 3 studies, maintenance therapywith lenalidomide resulted in a dou-bling of the time to disease progression.

CALGB 100104 Updated results of the CALGB

100104 trial, now with 18 months’ fol-low-up on 460 patients, were present-ed by Philip L. McCarthy, MD,Roswell Park Cancer Institute, Buffalo,NY. The study team randomized 570patients to lenalidomide (10 mg/day,with dose reduction or titrationallowed) or placebo after ASCT (and avariety of induction regimens). Time to disease progression (or

death) was significantly better in themaintenance arm (42.3 months) com-pared with placebo (21.8 months),although overall survival (OS) re -mained similar. The lack of differencemay be because most placebo recipi-ents were allowed to receive lenalido-mide when the study was unblinded.Of 100 placebo-treated patients, 86started treatment with lenalidomide

when the trial was unblinded.Of 211 lenalidomide-treated patients,

46 had disease progression or diedcompared with 95 of the 229 placebo

recipients (P <.001). This yielded a 60%reduction in the risk of progressionwith lenalidomide maintenance, DrMcCarthy reported. Lenalidomide prolonged time to

progression or death in patients withhigh and low beta 2-microglobulin lev-els (indicating disease risk) and inpatients with previous thalidomide orlenalidomide induction therapy.No significant OS advantage has

been observed, although a trendfavored maintenance, with 13 deathsin the lenalidomide arm and 24 in theplacebo arm (P <.052).“Some hematologic toxicity was

observed, but it was not severe,” henoted. In the lenalidomide arm, grade3 hematologic events were observed in31% of patients versus 7% with place-bo, and grade 4 events occurred in 14%versus 4%, respectively (P <.001).

IFM 2005-02 Supports MaintenanceLenalidomideUpdated analysis of the IFM 2005-02

trial, reported by Michel Attal, MD,Hospital Purpan, Toulouse, France,also supported lenalidomide mainte-nance in patients with MM. The study included 614 patients

aged ≤65 years who were randomizedpost-ASCT to receive consolidationwith lenalidomide (25 mg/d, 21 days/month, for 2 months) followed bymaintenance with either lenalidomide(10-15 mg/d) or placebo until relapse.After the first preplanned interimanalysis, with a median follow-up of24 months, the study was unblindedbecause of the superiority of thelenalidomide arm. The final analysiswas performed with a median follow-up of 34 months from randomization.

Consolidation with lenalidomide im -proved the very good partial responserate, and maintenance with the drugimproved progression-free survival(PFS). Median PFS was 24 months withplacebo and 42 months with lenalido-mide, for a very significant 50% reduc-tion in risk of disease progression. “There was about a 50% reduction

in the risk of progression in all sub-groups,” he said. “Today, deaths haveonly been observed in the high-riskpatients. Maintenance treatment withlenalidomide was not associated with

resistance of the disease at time of pro-gression. The median interval betweenprogression and death was similar inboth arms at 12 months,” Dr Attal said.“With the current follow-up, the 5-yearpostdiagnosis overall survival remainsextremely high (81%) and similar inthe 2 treatment groups.” Maintenance treatment with len -

alidomide was well tolerated, withtreatment interruptions no higher inthe active arm.

Concerns Over SecondMalignanciesAttendees at ASH 2010 welcomed

the findings of prolonged remissionwith lenalidomide maintenance, butsome specialists expressed concernover the finding of an excess number ofnew malignancies in the lenalidomidearms of the CALGB and IFM trials. In the CALGB study, 25 new malig-

nancies were reported—3 in the len -alidomide group (1 in a patienttreat ed for breast cancer) and 2 in theplacebo arm. A total of 15 malignan-cies occurred among the 231 patientsreceiving lenalidomide and 6 amongthe 229 receiving placebo. The exacttypes of cancers were not detailed,except for cases of acute myeloidleukemia/myelodysplastic syndrome(AML/MDS). In the IFM trial, hematologic malig-

nancies have been diagnosed in 10patients receiving lenalidomide versus2 receiving placebo; nonhematologiccancers have been diagnosed in 6patients versus 1 patient, respectively. Remarking on the CALGB results, Dr

McCarthy said, “We don’t know howthese patients were treated. We knowthey all got a big dose of the alkylatingagent, but we cannot say anything spe-cific. We will have to see if this holds upas something significant.”Thierry Facon, MD, of the Hospital

C. Huriez, Lille, France, pointed outthat the numbers of malignancies arevery small and that AML/MDS haslong been observed in MM.In a December 6, 2010, report on this

topic (www.reuters.com/article/2010/12/06/celgene-idUSN0620814320101206), Brian Gill, a spokes man forCelgene (lenalidomide maker) said itis known that about 8% of patientswith MM who are alive after 2 yearsare at risk for developing a second can-cer, and induction therapy greatlyincreases this risk. He maintained thatthe occurrence seen in these studiesfalls within the expected range. �

Maintenance Therapy with LenalidomideDoubled Remission TimeBy Caroline Helwick

“There was about a 50%reduction in the risk ofprogression in allsubgroups….The 5-yearpostdiagnosis overallsurvival remains extremelyhigh (81%) and similar in the2 treatment groups.”

—Michel Attal, MD

In the CALGB 100104 study,of 211 lenalidomide-treatedpatients, 46 had diseaseprogression or died comparedwith 95 of the 229 placeborecipients. This yielded a60% reduction in the risk of progression withlenalidomide maintenance.

dronate was superior to pamid ro -nate or ibandronate. ZA was superi-or to clodronate in PFS.The Medical Research Council

Myeloma IX study compared ZA,given intravenously monthly, withthe daily oral bisphosphonate clo-dronate among 1970 patients withnewly diagnosed MM. After a medi-an follow-up of 3.7 years, ZA pro-longed OS from 44.5 to 50.0 months,PFS from 17.5 to 19.5 months, andreduced the incidence of SREs from35.3% to 27.0% compared with clo-dronate, all significant differences.Cost-effectiveness was expressed

in terms of the incremental cost perquality-adjusted life-year (QALY)gained with ZA versus clodronate.Costs were in 2009/2010 Canadiandollars, discounted at 5% annually. The cost per QALY gained with

ZA versus clodronate in patientswith newly diagnosed MM fellbelow the standard threshold of

$50,000 per QALY gained. The expected lifetime costs (in -

cluding administration and monitor-ing costs) of bisphosphonate therapywere $11,967 greater with ZA thanwith clodronate ($14,267 vs $2301),but the expected costs of SREs werereduced by $720 with ZA ($4152vs $4872). The expected costs of adverse

events were increased by $663 withZA ($3225 vs $2562), and the expect-ed total lifetime costs were increasedby $11,878 ($30,103 vs $18,225).On an undiscounted basis, the life

expectancy with ZA increased by 0.83years (6.43 vs 5.60), QALYs increasedby 0.56 (from PFS and OS), and 0.02QALYs were lost as a result ofadverse events (predominantly jawosteo necrosis). The total QALYsgained with ZA (undiscounted),therefore, were 0.56 (4.43 vs 3.87). Ona discounted basis, total QALYsgained were 0.37 (3.51 vs 3.14). �

Cost-Effectiveness Analysis...Continued from page 23


Myelodysplastic Syndromes

At ASH 2010, 2 population-basedstudies investigated currenttreatment options for myelo -

dysplastic syndromes (MDS).

Efficacy Confirmed but Head-to-Head Comparison Needed A retrospective, population-based

study assessing the effectiveness ofcurrent treatments for MDS showedthat azacitidine and decitabine areequally effective, but azacitidine pro-duces higher response rates. The studywas from the University of SouthFlorida Center for Evidence-BasedMedicine, Tampa. Although studies have shown both

drugs to be more effective than sup-portive care, no studies have com-pared the 2 hypomethylating agentshead to head. “Our study is the firstpopulation-based direct comparison ofazacitidine versus decitabine,” saidTea Reljic, University of South FloridaClinical and Translational ScienceInstitute Center for Evidence-BasedMedicine and Health OutcomesResearch, Tampa.Investigators analyzed outcomes for

174 patients with MDS, who were alltreated at the H. Lee Moffitt CancerCenter, Tampa, between 1999 and2009; 121 received azacitidine and 53received decitabine.The unadjusted results for overall

survival and progression-free survivalshowed significant benefits for azaciti-dine, which improved these outcomesby about 50%. In the multivariate

analysis, however, these gains lost sta-tistical significance, Ms Reljic reported.Treatment with azacitidine com-

pared with decitabine, however, wasassociated with significant benefits inoverall response rates (20% vs 6%,respectively) and hematologic re -sponse rates (24% vs 6%, respectively),she added. Toxicities were also similarbetween the 2 groups. “These results warrant a prospective

direct comparison of the drugs in a ran-domized, controlled trial,” she said.

Cost and Utilization of AzacitidineThe cost and utilization of azaciti-

dine was investigated by a population-based study from Canada. “Based on the published treatment

regimen [Fenaux P, et al. Lancet Oncol.2009;10:223-232], the average cost ofazacitidine is estimated to be $10,000[Canadian dollars] per month,” saidPamela Skrabek, MD, FRCPC,CancerCare Manitoba. “With a medianof 9 full-dose cycles of the drug, thecost per patient is anticipated to be$90,000, which translates into a finan-cial constraint that prevents manyhealthcare systems from using thisdrug. We thought a population-basedstudy would provide a more realisticestimate of its use and cost and helpour center budget for it.” Azacitidine was provided by the

manufacturer on a compassionate(from April 2009 to March 2010) basisfor any patient who met the approvedcriteria. The analysis included 11

patients who were followed up to July2010 and received 42 cycles (median of3 cycles per patient). Dose reductions were required in 9

of 42 cycles as a result of cytopenias.Eleven of 42 cycles were complicatedby febrile neutropenia, with 7 of theseepisodes requiring hospital admission.Despite receiving dose reductions andfewer total cycles, 45% of the patientsstill had an objective response, DrSkrabek said. Reasons for discontinu-ing the drug were progressive cytope-nia or transformation to leukemia,ability to undergo stem-cell transplan-tation, occurrence of severe sepsis, andlack of response.

“In this population-based study,we demonstrate that many MDS

patients are withdrawn from furthertreatment due to adverse effects orlack of early response, in contrast topatients participating in clinical tri-als,” she explained. “Many patientsare older, sicker, and frailer, andwould have been excluded from atrial. Ours is a more typical popula-tion. In the real world, patients cannottolerate 9 cycles.” The approximate cost of azacitidine

in this cohort was $34,090 per patient,which was substantially lower than theanticipated cost. “We believe that peo-ple overestimate what it will cost to usethis drug,” she said in an interview.“We think that decisions to fund ordeny expensive drugs should includedata from population-based studies.” �

Therapies for Myelodysplastic Syndromes Improvingbut Still Fall Short

Myelodysplastic syndromes(MDS) are a group of disor-ders caused by poorly

formed or dysfunctional blood cells.Currently, 3 drugs are approved bythe US Food and Drug Admin istra -tion for treatment of MDS—azaciti-dine, decitabine, and len alidomide. Although each drug has helped to

improve the care of patients withMDS, “MDS treatment in 2010 ulti-mately failed in most patients,” saidWilliam Blum, MD, Ohio State Uni -versity Comprehen sive Care Center,Columbus.

Current TherapiesBut current therapies provide a

foundation on which to build, headded. The best available evidencefor this is that patients benefitingfrom therapy with azacitidine ordecitabine should continue treatmentuntil progression or unacceptable tox-icity, Dr Blum said, but the questionof which agent is superior is hard toanswer. A comparative trial recentlyopened, but overall survival (OS),“the more relevant question,” is not aprimary end point. Lenalidomide is approved for lower-

risk MDS patients with transfusion-dependent anemia and the chromoso-mal deletion (del)5q. Len alidomidecatapulted onto the MDS treatmentscene when it showed robust activity

(83% response rate) in patients who fitthis profile. Subsequent studies havedetermined that dose reductions areoften needed, and blood counts should

be followed weekly during the first 8weeks of therapy.

Prophylactic granulocyte colony-stimulating factor (G-CSF) is not neces-sary for safe administration of lenalido-mide. The drug is being studied inhigh-risk patients with del(5q) and inlower-risk patients without del(5q). Dr Blum pointed out that higher-

risk MDS patients who are otherwisehealthy are excellent candidates fortreatment. The drug used must beapplied in repetitive cycles andadministered to appropriate patientswho are able to undergo prolongedtherapy, he emphasized. “With bothazacitidine and decitabine, mainte-nance of response with continuedtherapy is clearly important,” he said,“thus, in the absence of unacceptable

“We think that decisions to fund or deny expensive drugsshould include data from population-based studies.”

—Pamela Skrabek, MD, FRCPC

First Population-Based Comparisons of Azacitidineand Decitabine for MDSSimilar Effectiveness, Varied Response RateBy Caroline Helwick


“With both azacitidine anddecitabine, maintenance ofresponse with continuedtherapy is clearlyimportant.”—William Blum, MD


Other Highlights

setting of relapsed/refractory disease;the rate of very good partial respons-es or better was 37%. The combina-tion appears to be synergistic, saidPaul G. Richardson, MD, HarvardMedical School.

Pomalidomide, a novel im muno -modulatory agent, was very active incombination with dexamethasone in 92patients with advanced MM refractoryto bortezomib and lenalidomide. Xavier Leleu, MD, Hopital Huriez,

Lille, France, said that overall sur-vival was >85% at 6 months, and at amedian follow-up of about 7 months,median progression-free survival(PFS) ranged from 7 to 10 months,depending on the regimen. Resultssuggest that pomalidomide has nocross-resistance with lenalidomide(see page 22).

Carfilzomib, a novel highly selec-tive next-generation protease inhibitor,achieved durable responses in a phase2b study of 266 patients withrelapsed/refractory MM previouslytreated with all available therapies.Among 257 patients, responses wereobserved in 24.1%, and median dura-tion of response was 8.3 months. The clinical response rate (complete

or partial remission or stable disease)was 34.2%. Median overall survivalwas 15 months. The most commongrade 3 or 4 toxicities were thrombo-cytopenia (27%), anemia (22%), lym-pho penia (18%), and neutropenia(10%). Carfilzomib may be of clinicalbenefit to patients who have relapsedor are refractory to other therapies,said David Siegel, MD, St. JohnTheuer Cancer Center, Hackensack,NJ (see page 22).

Chronic Myelogenous LeukemiaBosutinib, a new tyrosine kinase

inhibitor with a dual mechanism ofaction, may turn out to be a newoption for first-line therapy for CML,to be added to the current agentsapproved by the US Food and DrugAdministration as first-line therapy forthis condition—imatinib, dasatinib,and nilotinib. Promising results of a randomized,

phase 3, open-label trial of bosutinibwere reported at the meeting. In 502newly diagnosed patients with CMLevaluated at 1 year, the major molecularresponse rate was 39% with bosutinibversus 26% with imatinib (P = .002). According to Carlo Gambacorti-

Passerini, MD, University of MilanoBicocca, Italy, bosutinib’s effect ontreatment failure is the main messageof this study. At 1 year, treatment fail-ures occurred in 3% of patients treat-ed with bosutinib versus 10% of thosewho received standard imatinib. The overall net benefit of 7% would

translate to about 500 newly diag-nosed patients with CML in theUnited States each year, he said (seepage 16).A very preliminary but very positive,

dose-escalation phase 1 study of 74patients suggests that ponatinib—anovel tyrosine kinase inhibitor—will bethe first drug to inhibit the entire spec-trum of mutations responsible forresistance to tyrosine kinase inhibitors,including the T315I mutation, whichhas so far eluded drug treatment.Responses were most robust in chronic-phase patients with T315I mutations,but were less robust in accelerated andblast-phase CML.Jorge Cortes, MD, of M. D. Anderson

Cancer Center, Houston, called theresults of this study “very exciting,”and said that ponatinib may turn outto be the first drug that can prevent theemergence of resistance resulting frommutations in this patient population(see page 16).

Non-Hodgkin LymphomaPixantrone, a novel aza-anthra -

cenedione structurally related tomitoxantrone and anthracyclines,achieved superior rates of completeresponse/complete response uncon-firmed, a superior overall response

rate, and superior PFS versus com-parator agents in the randomizedphase 3 EXTEND trial of 140 heavilypretreated patients with non-Hodgkinlymphoma who have poor prognosis. Ruth Pettengell, MD, of St. George’s

Hospital in London, United Kingdom,reported the results of the study.

At 18 months of follow-up, therates for pixantrone versus compara-tors, respectively, were:• Complete response/complete re -sponse unconfirmed—20% versus5.7%

• Overall response—37.1% versus14.3%

• Median PFS—5.3 months versus 2.6months

• Median overall survival 10.2 monthsversus 7.6 months.

Hodgkin LymphomaBrentuximab vedotin, an anti-

body-drug conjugate of an anti-CD30monoclonal antibody and a potentantitubulin agent called monomethylauristatin E, showed encouragingresults in patients with relapsed/refractory Hodgkin lymphoma in apivotal phase 2, single-arm studyreported by Robert Chen, MD, assis-tant professor, City of Hope, Duarte,CA (see page 15). Dr Chen called these results “dra-

matic” for patients with Hodgkin lym-phoma who have limited or no treat-ment options. Of 102 high-risk patientswith refractory or relapsed disease,75% had an objective response (≥50%tumor shrinkage), and 94% had somedegree of tumor shrinkage. �

Hematology Drug Pipeline... Continued from page 1

For too many patients with hema-tologic malignancies, the hopethat comes with potentially

being cured through an allogeneic(donor) stem-cell transplant is oftentempered by the devastating cost oftransplant-related complications. Im -proving pretransplant prediction ofcomplications and posttransplantrecognition and treatment shouldimprove outcomes for patients, butthe pace has been slow.Mohamed L. Sorror, MD, MSc, of

the Fred Hutchinson Cancer ResearchCenter and the University ofWashington, Seattle, described thegeneral lack of standardization inhow transplant physicians use pre-

transplant comorbidities to predictthe risk of toxicity after allogeneicstem-cell transplant. He showed compelling evidence

that the use of a hematopoietic-celltransplantation comorbidity index—which compiles objective organcomorbidities into a single risk fac-tor—is a more standard and effectiveway to predict transplant-related tox-icities. Dr Sorror gave examples ofhow this index may be used, forexample, in considering a reduced-intensity conditioning regimen inpatients with increased hematopoiet-ic-cell transplantation comorbidityindex scores and myeloablative con-ditioning regimens in older patients

Long-Term Complications ofStem-Cell TransplantBy Caroline Helwick

toxicity or evidence of disease pro-gression, therapy should be contin-ued indefinitely.”When properly administered, even

elderly patients (>75 years) can havea survival benefit (2-year OS is 55%)with good tolerability, he said.

ToxicityAdverse events are inevitably

encountered in treating patientswith MDS with these drugs.Hematologic toxicity is common,and concern for infection in the set-ting of disease- or drug-related neu-tropenia has led to frequent prophy-lactic use of myeloid growth factors. However, there is little evidence

that this improves outcomes, accord-ing to Dr Blum. “Growth factors canadd considerable cost and patientinconvenience to the regimen….Judicious use of G-CSF in the settingof ongoing neutropenic infection,particularly for patients with pre-dominantly drug-associated neu-tropenia, is quite reasonable but notnecessarily mandated. I typically useG-CSF only in the setting of seriousneutropenic infection, when it isclearly drug-related.”

The role of immunosuppressivetherapy with antithymocyte globu-lin and cyclosporine “remains enig-matic” in MDS. “The serious toxici-ties that can be encountered with itsinfusion and long-term immunosup-pressive effects have properly led tohesitation over its use in practice…although appropriate selec tionof patients affords some opportunityfor prolonged responses without therequirement for repeated mainte-nance chemotherapy,” Dr Blum said.He added that immunosuppressivetherapy could be considered in lieuof a hypomethylating agent (ie, aza -citidine, decitabine) for a selectgroup of previously untreated,younger patients in accordance withclinical guidelines.Looking ahead, he said “the great-

est benefit from each of the currentagents will be in providing momen-tum for the next decade of research.Future advances will come from thediscovery of new molecular targetsand development of prognostic andpredictive markers, as well as de -velopment of novel therapeuticapproaches, including allogeneictransplantation.”—CH �

Therapies for Myelodysplastic...Continued from page 25



Other Highlights

Key advances in understandingthe human genome, and the de -velo pment of high-throughput

methods of defining genetic loci, areaccelerating the pace of discovery in allcancer, especially hematology, it seems.At ASH 2010, a number of sessions

were aimed at drilling down to thelevel of the chromosome. Althoughchromosomal alterations have, forsome time now, defined subsets ofpatients with leukemia and led toamazing treatments, such as imatinib,the search for key genes is under wayin virtually all categories of hemato-logic disorders and malignancies. Genomic studies were the focus of

many abstracts and entire sessions atthe meeting. Mark D. Fleming, MD,DPhil, of Harvard Medical School,who moderated one of the sessions,suggested that attendees should begin

to understand “the principles ofgenome-wide association studies andhow the results may be translated toclinical medicine.”

For example, European population-based studies have identified 70 singlenucleotide polymorphisms that are

associated only with platelet countand volume. And genome-wide inter-rogations are now addressing the eti-ology and responsiveness to therapyfor childhood acute lymphoblasticleukemia (ALL). A collaborative study has identified

single nucleotide polymorphisms thatare significantly associated with ALL,some of which distinguish among sub-types and others that are associatedwith methotrexate pharmacokinetics,known to be important in ALL treat-ment response. Genes have been identified in asso-

ciation with a virulent subtype of pedi-atric leukemias that occurs in infantsand in secondary leukemias after cer-tain therapies. Other investigators arepinning down genes that may help indonor selection for hematopoieticstem-cell transplantation, and one

gene deletion is now known to beassociated with the occurrence ofgraft-versus-host disease afterward. The hemophilias are now consid-

ered prototypic models of genetic dis-ease and new therapies. Cloning ofthese genes led to the development ofrecombinant clotting factor concen-trates that revolutionized treatmentfor this disease. Bioengineering is now focused on

developing new second- and later-generation concentrates that persistlonger in the body and may result inreduced immunogenicity. Gene therapy approaches are

advancing in this area. These are onlya few examples of the genome-basedresearch exploding in hematologythat will ultimately lead to finelytuned, individualized therapy—butat what cost? �

Looking Ahead: Incorporating Genomic Researchinto Personalized MedicineBy Caroline Helwick

Hematologists should begin tounderstand “the principles ofgenome-wide associationstudies and how the resultsmay be translated to clinical medicine.”

—Mark D. Fleming, MD, DPhil

with lower scores. But questions will need to be

answered, he added, before thisapproach could be put into routinepractice:• Will mitigation of toxicity affect clin-ical outcomes?

• Should allogeneic stem-cell trans-plant even be offered to patientswith a hematopoietic-cell transplan-tation comorbidity index above acertain score?

Long-Term ComplicationsMohamad Mohty, MD, PhD, of the

CHU de Nantes in France, noted thatalthough more allogeneic stem-cell

transplant recipients are survivingthe early transplant period, they oftenexperience long-term medical com-plications and increased risk of mor-tality down the road. These complica-tions include:• Endocrine disorders• Secondary malignancies• Chronic graft-versus-host disease.Increased awareness and monitor-

ing for these conditions; appropriatemanagement strategies; and close part-nering among transplant centers,organ-specific specialists, and local pri-mary care providers will help to ame-liorate these problems, Dr Mohty said.Good quality of life after allogeneic

stem-cell transplant, therefore, isnever assured, said Margaret F.

Bevans, RN, PhD, of the NationalInstitutes of Health. She emphasizedthe multiple dimensions that affecthealth-related quality of life inpatients with allogeneic stem-celltransplant—physical, psychosocial,and emotional issues surface forpatients—and there can be great care-giver distress. Her group is develop-ing formal guidelines to assist trans-plant centers in assessing thesedomains.The speakers agreed that cure is no

longer enough in patients with hema-tologic malignancies; healthcare pro -viders must also ensure that life aftertransplant is worth living. �

Long-Term Complications... Continued from page 26

Multiple dimensions affecthealth-related quality of life in patients with allogeneic stem-cell transplant—physical,psychosocial, and emotionalissues surface for patients—and there can be great caregiver distress.

©2011 Millennium Pharmaceuticals, Inc. All rights reserved.

To learn more, visit us at millennium.com.

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ASH 2010: Payers' Perspectives

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