ASCO 2015 LYMPHOMA UPDATE

Dr Chandan

Lenalidomide in combination with rituximab for relapsed or refractory mantel cell lymphoma: Updated analysis of a phase 2 trial.

• Yucai Wang, Maria Lourdes Dela Rosa, Shouhao Zhou, Maria Badillo, Alicia Addison, Liang Zhang, Hun Ju Lee, Jorge Enrique Romaguera, Michael Wang; Rutgers New Jersey Medical School, Newark, NJ; The University of Texas MD Anderson Cancer Center, Houston, TX

J Clin Oncol 33, 2015 (suppl; abstr 8542)

Study characteristic

• Relapsed refractory MCL • single arm phase 1/2 trial• Lenalidomide 20 mg daily days 1-21 of each 28-day cycle• Rituximab 375 mg/m2 weekly during the first cycle only.• Treatment was continued until disease progression, stem-cell

transplantation, or severe toxicity. • The primary endpoint :ORR and the secondary endpoint OS. • Analysis by intention to treat.

Result• 46 patients • The median age was 66.5 (range 46-85).• Median number of prior lines of therapy was 2 (range 1-4).• At a median follow up of 24.7 months (range 1.2-96.1),• CR: 16 (34.8%) PR: 10 (21.7%) ,ORR of 56.5%. SD: 10 (21.7%) patients • ORR was independent of age, gender, number of prior lines of therapy and.• Median time to response was 1.8 months (range 1.6-7.7). Median duration of response was 20.9

months (95% CI 10.9-NR). • The median PFS was 14.1 months (95% CI 8.2-26.7), The 12- and 24-month PFS rates were 53.1% and

39.9%, respectively • The median OS was 24.6 months (95% CI 16.8-33.7) The 1-, 2- and 5-year OS rates were 82.6%,

52.2% and 26.1%, respectively.• Lower Ki-67 at registration ( < 50%) and fewer prior lines of therapy ( < 2) were predictive of better

PFS (HR = 0.242, 95% CI 0.070-0.715, P = 0.012; and HR = 0.245, 95% CI = 0.071-0.841, P = 0.025) and OS (HR = 0.267, 95% CI 0.110-0.648, P = 0.003; and HR = 0.363, 95% CI = 0.147-0.896, P = 0.028).

“Lenalidomide plus rituximab is efficacious in treating R/R MCL with good ORR (55%) with durable response (>20 month)”

Updated results of a phase II trial of brentuximab vedotin combined with R-

CHOP in frontline treatment of patients with high-intermediate/high-risk diffuse large B-

cell lymphoma (DLBCL).

Nancy L. Bartlett, Charles M. Farber, Christopher A. Yasenchak, Stephen Maxted Ansell, Ranjana H. Advani, Mark H. Knapp, Luis Fayad, Kathryn S. Kolibaba, Dipti Patel-Donnelly, Mahesh Seetharam, Habte Aragaw Yimer, Thomas John Manley, John M. Burke, Beata Holkova, L. Elizabeth Budde, Ahmad Sami Halwani;

Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO; Hematology-Oncology Associates of Northern New Jersey and Pennsylvania Carol G. Simon Cancer Center/US Oncology Research, Morristown, NJ; Willamette Valley Cancer Institute and Research Center/US Oncology

Research, Springfield, OR; Mayo Clinic, Rochester, MN; Stanford University Medical Center, Stanford, CA; Mid-Ohio Oncology/Hematology Inc., Columbus, OH; The University of Texas MD Anderson Cancer Center, Houston, TX; Northwest Cancer Specialists/US Oncology Research, Vancouver, WA; Virginia Cancer

Specialists/US Oncology Research, Fairfax, VA; Arizona Oncology Associates/US Oncology Research, Phoenix, AZ; Texas Oncology-Tyler/US Oncology Research, Tyler, TX; Seattle Genetics, Inc., Bothell, WA; Rocky Mountain Cancer Centers/US Oncology Research, Aurora, CO; Virginia Commonwealth University Massey

Cancer Center, Richmond, VA; City of Hope National Medical Center, Duarte, CA; University of Utah Huntsman Cancer Institute, Salt Lake City, UT

Study characteristic

• 53 pt: 6# BV+R-CHOP: 1.2 or 1.8 mg/kg BV q3 wks • Inclusion criteria IPI>3–5 or age-adjusted IPI (aaIPI) scores of 2–3 (high-

intermediate/high risk).• 62% were high-intermediate risk (IPI 3, aaIPI 2) ,38% were high risk (IPI

4-5, aaIPI 3). • 70%:stage IV disease • 28% had an ECOG PS 2. • Due to an increased rate of G3 neuropathy seen early in the 1.8 mg/kg

BV+RCHOP arm (30% vs 8%), treatment continue at 1.2 mg/kg BV+R-CHOP.

Result

• ORR: 97% with PET CMR 80% • CR: 1.2 mg/kg BV+RCHOP 86% 1.8 mg/kg BV+R-CHOP, 75% • CD30+ pts (n=13): CR 92% vs CD30– pts (n = 16) CR 69%. • CR rates were similar between ABC and GCB subtypes. • Treatment-emergent adverse events (AEs) occurred in 96% • ≥ G3 febrile neutropenia (27%), and anemia (24%). • AEs of neuropathy (mostly G1/2) occurred in 55% (38%, 1.2 mg/kg

BV+R-CHOP; 77%, 1.8 mg/kg BV+RCHOP).

“BV+R-CHOP has encouraging activity in frontline high-intermediate/high risk DLBCL; with CR rate in CD30+ pts was higher than in CD30– pts.

In combination with R-CHOP, BV is better tolerated at 1.2 mg/kg than 1.8 mg/kg due to reduced neuropathy.”

“

Effect of prednisone and rituximab prephase on early toxicity in older DLBCL patients (pts) receiving RCHOP within a NHL specific comprehensive geriatric assessment (CGA) trial.

• Colette Ngozi Owens, Augustine Iannotta, John F. Gerecitano, Matthew J. Matasar, Ariela Noy, Craig H. Moskowitz, Pamela Drullinsky, Maria Lia Palomba, David J. Straus, Steven M. Horwitz, Andrew David Zelenetz, Carol S. Portlock, Anita Kumar, Paul A. Hamlin; Memorial Sloan Kettering Cancer Center, New York, NY; Memorial Sloan Kettering Cancer Center, Englewood, NJ; Memorial Sloan Kettering Cancer Center, Rockville Centre, NY

Study characteristics

• Eligible pts (n = 30) de novo DLBCL/tDLBCL, • age ≥ 70 yrs or ≥ 60 yrs with KPS < 80%, and planned RCHOP-like

therapy for 2+ cycles. • CGA :CARG +CRASH scores as largely self administered assessments.

CGA was assessed at baseline, post pre-phase, with each cycle, and at end-of-therapy. • Pre-phase : Pred 50-100mg x 5-10 days + R 375mg/m2 x1 day

completed in the 14 days pre-RCHOP. • The study is powered to show a 15% change in CGA risk score, with

secondary endpoints of toxicity, TRM, PFS/OS.

Cancer and Aging Research Group - Chemo Toxicity Risk Score

Result

• median age 75 (range 65-85), female 59%• DLBCL 87%, Stage III/IV 60%, aaIPI high-int/high 57%• cell of origin GC/non-GC 55%/45%• median ki67 70% (range 60-90%). • 97 % completed pre-phase and 2+ cycles of chemotherapy. • Median followup is 6m (range 1-18m) with 28/30 pts alive.

RESULT

BASELINE POST PREPHASE

KPS median 70% 80%

CGA predicted risk of G3+ toxicity 65%(range 32-89%) Toxicity risk score 31% (9/29) pts, mean 16% risk reduction for G3+ toxicity

non-heme grade 3+ events were 41% andheme G4+ events 16%.

no reported TLS or early TRM (n = 30

“A pre-phase intervention of Pred and R may mitigate early toxicity, resulting in improved KPS and CGA risk score, with no TLS or early TRM”

GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma

• Laurie Helen Sehn, Neil Sun Chua, Jiri Mayer, Gregory Scott Dueck, Marek Trněný, Kamal Bouabdallah, Nathan Hale Fowler, Vincent Delwail, Oliver W. Press, Gilles A. Salles, John G. Gribben, Anne Lennard, Pieternella J. Lugtenburg, Natalie Franklin, Elisabeth Wassner Fritsch, Guenter Fingerle-Rowson, Bruce D. Cheson; BC Cancer Agency, Vancouver, BC, Canada; Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada; Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Medical Oncology, BC Cancer Agency, Kelowna, BC, Canada; First Faculty of Medicine, Charles University General Hospital, Prague, Czech Republic; Department of Haematology, CHU Haut-Lévèque, Pessac, France; The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Oncology-Hematology and Cell Therapy, University Hospital, Poitiers, France; Fred Hutchinson Cancer Research Center, Seattle, WA; Hospices Civils de Lyon, Université Claude Bernard, Pierre Bénite, France; Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom; Department of Hematology, Erasmus MC Cancer Insitute, Rotterdam, Netherlands; Biostatistics, F. Hoffmann-La Roche, Welwyn Garden City, United Kingdom; Pharma Development Oncology, F. Hoffmann-La Roche, Basel, Switzerland; Georgetown University Hospital, Washington, DC

Study characteristics

• GADOLIN (NCT01059630) is a phase III open label study I• Primary endpoint was PFS assessed by an independent radiology

facility (IRF), with 80% power to detect 43% improvement in median PFS. CD20+Rituximab Refractory

396 pts

Bendamustine 120 mg/m2 D1/2+G 1000 mg d1, 8, 15 #1, d1 #2-6 N=194

PD- BSC

Any response: G every 2 mo for up to 2 yrs

Bendamustine 120 mg/m2 D1/2+N=198

Result

• Median age was 63 yrs and pts had a median of 2 prior therapies

• Median PFS was 14 mo for B and 29 mo for GB (HR 0.52, 95% CI 0.39–0.70; p < 0.0001). OS Not reached• • There were no significant differences in IRF-assessed ORR (63.0% B vs 69.1%

GB) or CR (12.2% B vs 11.2% GB) at end of induction

• fewer Grade ≥ 3 adverse events with B than GB (62.1% B vs 68% GB), notably neutropenia (26.3% B vs 33.0% GB) and infusion-related reactions (3.5% B vs 8.8% GB)

“First randomized evidence of benefit for a novel aCD20 mAb in Rit-Ref iNHL” “G combined with B (90 mg/m2) followed by G maintenance significantly improved PFS vs B alone (120 mg/m2) in Rit-Ref iNHL.”