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Induction Therapy For Multiple Myeloma: Two vs Three Drug Regimen and Role of Risk Stratification Ravi Vij MD Associate Professor Section of BMT and Leukemia.

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Presentation on theme: "Induction Therapy For Multiple Myeloma: Two vs Three Drug Regimen and Role of Risk Stratification Ravi Vij MD Associate Professor Section of BMT and Leukemia."— Presentation transcript:

1 Induction Therapy For Multiple Myeloma: Two vs Three Drug Regimen and Role of Risk Stratification Ravi Vij MD Associate Professor Section of BMT and Leukemia Washington University School of Medicine

2 Trends in Overall Survival of MM Overall survival 1971–2006 Diagnosis period Median OS 1996– months 1971– months (P<0.001) Kumar SK, et al. Blood. 2008;111: Time from diagnosis (Months) Survival – – – – – – –1976 OS, overall survival. 2 M

3 CR and MM Is CR an adequate surrogate for OS? Are all CRs as durable? Should we strive for CR pre-transplant? What is the role of HDCT for patients in CR pre-transplant?

4 CR associated with OS prolongation in post- induction and post-transplant settings Lahuerta et al. J Clin Oncol. 2008;26(3): Alexanian et al. Bone Marrow Transplant. 2001;27: Wang, et al. Bone Marrow Transplant. 2010;45(3): Survival by response for 291 patients with MM (age <70 y) who received chemotherapy alone (left) and 375 who proceeded to ASCT (right) (CR vs PR or NR P<0.01) Chemotherapy Alone Chemotherapy and ASCT 4

5 > 65 yrs > 75 yrs Importance of CR in Elderly MM Gay F et al. Blood. 2011;117(11): )

6 Approach to Treatment of MM Clearly not a transplant candidate based on age, performance status and comorbidity Conventional Therapy Potential transplant candidate Non-alkylator based induction x 4 cycles Stem cell harvest

7 Bortezomib-Based Induction Prior to SCT TrialRegimenN CR+VGPR Post- Induction (%) CR+VGPR Post-ASCT (%)PFSP Value Cavo et al, 2010 VTD vs TD * 28 82* 64 68% at 3 yr 56% at 3 yr.0057 Moreau et al, 2011 IFM 2007/02 VD vs vTD ‡ § Median 30 months Median 26 mo.22 *P <.001; † P =.001; ‡ P =.05; § P =.02 GMMG= German Multiple Myeloma Group; SCT = stem cell transplant; CR = complete response; VGPR = very good partial response; PAD = bortezomib (V)/AD; T = thalidomide; VAD = vincristine, doxorubicin (A), dexamethasone (D); vTD = reduced-dose bortezomib. Cavo M, et al. Lancet. 2010;376: Harousseau JL, et al. J Clin Oncol. 2010;28: Sonneveld P, et al. ASH Annual Meeting Abstracts. 2010;116(21):40. Accessed July 17, Moreau P, et al. Blood. 2011;118:

8 Fayers PM et alBlood.2011;118(5): MPT vs MP in Elderly MM

9 Median survival: MP 32.7 months (95% CI, months) MPT 39.3 months (95% CI, months). HR 0.83 (95% CI: ) P=0.004 Overall Survival

10 Palumbo et al. N Engl J Med 2012;366: MPR vs MP in Elderly MM

11 StudyRegimenNORRCR/nCROutcomes VISTA San Miguel et al. Mateos et al. Phase III VMP MP % 35% 33% 4% 5 yr OS: 46% 5 yr OS: 34.4% UPFRONT Niesvizky et al. Phase III VMP/Vel VTD/Vel VD/Vel % 79% 71% 31% 36% 34% ORR: overall response rate; CR: complete response; nCR: near complete response; OS: overall survival; TTP: time to progression; PFS: progression free survival; VMP: Bortezomib-melphalan-dexamethasone; MP: Melphalan- Prednisone; VTP: Bortezomib-thalidomide-dexamethasone; VTD: bortezomib-thalidomide-dexamethasone; VD: bortezomib-dexamethasone; VMPT-VT: bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance Bortezomib in Transplant Ineligible MM

12 UPFRONT Study

13 MM-020: Len + Low-dose Dex vs MPT in Previously Untreated MM Protocol CC-5013-MM-020/IFM ; data on file, Celgene Corporation Inclusion criteria Previously untreated MM Age  65 years or not a candidate for transplantation No neuropathy of grade > 2 CI Cr > 30 ml/min Lenalidomide 25 mg/day, days 1–21, every 28 days Dexamethasone* 40 mg/day, days 1, 8, 15, 22, every 28 days Until PD Lenalidomide 25 mg/day, days 1–21, every 28 days Dexamethasone* 40 mg/day, days 1, 8, 15, 22, every 28 days 18 four- week cycles or until PD N = 1,590 Centres in EU, Switzerland, USA and Canada *In patients older than 75 years Dexamethasone 20 mg/day Thalidomide 100 mg/day Melphalan 20 mg/kg/day Melphalan 0.25 mg/kg/day, days 1–4, every 42 days Prednisone 2.0 mg/kg/day, days 1–4, every 42 days Thalidomide* 200 mg/day, days 1–42, every 42 days 12 six- week cycles or until PD

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16 Conclusions Three drug induction regimen are associated with higher CR rates compared to two drug regimen. In the transplant eligible population prospective trials have shown a higher CR rate and PFS for two drug regimen. Follow-up is too short for analyses of OS. In the transplant ineligible population three drug regimes of thalidomide and bortezomib have a OS advantage compared with MP. Whether non-melphalan containing two drug regime may be equivalent is the subject of ongoing trials. We have entered an era of risk stratification for deciding therapy. However no consensus has emerged on treatment paradigms.


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