Multiple Myeloma
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Dr. Alan Teh , 2012
Multiple Myeloma
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Sarah Newbury, the first reported patient with multiple myeloma.
A) Bone destruction in the sternum. (B) The patient with fractured femurs and right humerus. (C) Bone destruction involving the femur.
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Timeline depicting the history and treatment of multiple myeloma from 1844 to the present.
Kyle R A , Rajkumar S V Blood 2008;111:2962-2972
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Myeloma is a blood cancerIncidence : 0.7M/0.5 F per
100,000 population (NCR, 2003)
Median age: 60 years1/10 as common as leukaemias
What Is Multiple Myeloma?
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Causes
Is not known for sureDecline in the immune systemBiological factorsCertain occupationsExposure to certain chemicals Exposure to radiationVirus
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What Is Multiple Myeloma?Cancer of plasma cells.Plasma cells come from B lymphocytes, and
produce antibodies (immunoglobulins). Myeloma cells produce abnormal
immunoglobulins.– Overproduce monoclonal protein or paraprotein.– Ineffective immunoglobulins.– Leads to decreased bone marrow function. – Destruction of bone tissue.
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Plasma Cell
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Mechanism of diseasePlasma cell proliferation - > anemia, bone
marrow suppression, infection risk
Osteoclasts - > boney lesions, fractures, increased blood calcium
Paraprotein, hypercalcemia -> renal failure
Hypercalcemia – polyuria, thirst, drowsiness, coma
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MM: Clinical PresentationsAnemia - 73 percentBone pain - 58 percentElevated creatinine - 48 percentFatigue/generalized weakness - 32 percentHypercalcemia- 28 percentWeight loss - 24 percent, one-half of whom
had lost ≥ 9 kgEarly stage - asymptomatic
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Common Sites for Bone InvolvementSkullSpine
ThoracicLumbarVertebrae
PelvisLong bones Spinal cord –
compression can occur
http://www.emedicine.com/Radio/topic460.htm#section~Introduction
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Slowly evolving cancerMGUS
Monoclonal Gammopathy of Unknown Significance
Asymptomatic myeloma
Symptomatic myeloma
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Risk of MGUS Myeloma
Risk groupRelative
RiskRisk @ 20
yrs
Lowest risk: 1. M protein < 1.5 g/dL2. IgG subtype3. Normal FLC ratio
1 5%
Any 1 factor abnormal 5.4 21%
Any 2 factors abnormal 10.1 37%
All 3 factors abnormal 20.8 58%
Rajkumar, V et al. Blood . 2005
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When I told a friend that I have cancer, he replied "I thought you were an Aries?".
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Symptomatic myeloma= CRABhyperCalcaemiaRenal insufficiencyAnaemiaBone lesions
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DiagnosisParaprotein (M-protein)
serum protein electrophoresis24 hr urine protein electrophoresisserum Free light chain
Bone marrow biopsyplasma cellschromosome analysis: Karyotyping, FISH
ImagingX Rays, MRI, PET scan
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SPEP: Normal
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SPEP: M-protein, M-spike
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Bone Marrow
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Cytogenetics
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FISH
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Normal Skull Xray
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Lytic Bone Lesion
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MM: PET Scan
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Staging for MMInternational staging system (ISS)
Stage I — B2M <3.5 mg/L and serum albumin ≥3.5 g/dL
Stage II — neither stage I nor stage IIIStage III — B2M ≥5.5 mg/L
Median overall survival for patients with ISS stages I, II, and III are 62, 44, and 29 months
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Cytogenenetics, FISHHigh risk (median survival 25 months): Intermediate risk (median survival 42
months)Standard risk (median survival 50 months)
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What's the difference between God and a doctorGod doesn't think he’s a doctor
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Cancer cures smoking, eventually
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Previous Challenges in MM Treatment • Currently incurable in most patients.• Long-term complete responses are rare. • Median survival with standard therapy
about 3 years.• Autologous stem cell transplant may
prolong progression free survival, but it’s not curative.
• Treatment of relapse:– No standard therapy. – Existing options inadequate.
New treatment options needed.
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MM Treatment OptionsConventional chemotherapy:
Melphalan Doxorubicin Cyclophosphamide
• Radiation therapy
• Stem cell transplantation:
– Autologous– Allogenic
• Novel therapeutics: – Thalidomide – Lenalidomide – Bortezomib
Thalomid® Prescribing Information, Revlimid® Prescribing Information; Velcade® Prescribing Information
• Steroid therapy: – Dexamethasone – Prednisone
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MM: Treatment DecisionsIndications for treatmentRisk stratification
- age- co-morbidities
Eligibility for stem cell transplantation
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Smoldering (asymptomatic) myelomaDeferral of chemotherapy until progression to
symptomatic diseaseFollow these patients closely, every 3 to 4
months, with serum protein electrophoresis, complete blood count, serum creatinine, and serum calcium
Metastatic bone survey should be considered annually because asymptomatic bone lesions may develop
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MM: Indications for TreatmentAnemia (hemoglobin <10 g/dL or 2 g/dL
below normal)Hypercalcemia (serum calcium >11.5 mg/dL)Renal insufficiency (serum creatinine>2
mg/dL)Lytic bone lesions or severe osteopeniaExtramedullary plasmacytoma
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Current Frontline Options
Conventional chemotherapySurvival ≤ 3 yrs
TransplantationProlongs survival 4-5 yrs
Novel agents targeting stromal interactions and associated signaling pathways have superiority over conventional chemotherapy- increased % total responders- increased depth of response
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Myeloma treatment optionsEra of Novel therapy as frontline >
Conventional chemotherapy
Autologous transplantation (high dose chemotherapy and stem cell rescue) still an option for younger patients
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Current Frontline Options
Examples of current Novel agent combinations:
Thalidomide based : TD, CTD, MPT
Bortezomib (Velcade) based: Vdex, VMP, CVD, PAD, VRD
Lenalidomide (Revlimid) based: LenDex, Lendex
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Younger patientsTimingUpfront after initial therapy with
novel agentsSalvage for relapseSingle vs Tandem (Double)Low TRM - <3%
Autologous transplantation
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Autologous transplant - ineligible Age >70 yearsSignificant comorbities (organ
function)Poor performance status
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Allogeneic transplantationGenerally not recommended (outside
of clinical trials)High incidence of GVHDHigh TRM (> 40%)
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RadiotherapySurgeryBone care – bisphosphonatesTransfusionsGrowth factors Treatment and prevention of
infections Monitoring, management and
prevention of s/e
Other treatment / Supportive care
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Myeloma survival by decade
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Assessment of response
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Impact of Novel Therapies on Survivorship Care
Unexpected new long-term complicationsSecond cancersLong-term maintenance for survivors:
quality of lifeFamily/social problemsFinancial/insurance concernsOther
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Optimizing Survival: Importance of Health MaintenanceMM patients are expected to live longerProper health maintenance contributes
toward longer survival and quality of life
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RelapseBiochemical
- significant increase in M-proteinClinical
- CRAB criteriaImportance of monitoring and
follow-up
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Hope New drugs on the horizonCarfilzomibPomalidomidePanobinostatVorinostatElotuzumabOld drugs with new useBendamustine
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Be informedhttp://myeloma.orgGroup support
meetingssupport groups
http://malaysianmedicine.com – Myeloma Support Group
Support
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Mobile app
Myeloma Info mobile applicationmobile browser:http://malaysianmedicine.com/myelomainfo
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