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Ravi Vij MD Associate Professor Section of BMT and Leukemia

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. 1989–1994. 1995–2000. 2001–2006. M. Trends in Overall Survival of MM. 1.0.

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Ravi Vij MD Associate Professor Section of BMT and Leukemia

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  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. 1989–1994 1995–2000 2001–2006 M Trends in Overall Survival of MM 1.0 Diagnosis period Median OS 1996–2006 45 months 1971–1996 30 months (P<0.001) 0.8 2001–2006 OS, overall survival. 0.6 Survival 0.4 1971–1976 0.2 1977–1982 1983–1988 0 0 20 40 60 80 100 120 140 Time from diagnosis (Months) Overall survival 1971–2006 Kumar SK, et al. Blood. 2008;111:2516-2520.

  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 settings1-3 Chemotherapy Alone Chemotherapy and ASCT 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) 1. Lahuerta et al. J Clin Oncol. 2008;26(3):5775-5782. 2.Alexanian et al. Bone Marrow Transplant. 2001;27:1037-1043. 3. Wang, et al. Bone Marrow Transplant. 2010;45(3):498-504.

  5. Importance of CR in Elderly MM > 65 yrs > 75 yrs Gay F et al. Blood. 2011;117(11):3025-3031)

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

  7. Bortezomib-Based Induction Prior to SCT *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;376:2075-2085. Harousseau JL, et al. J ClinOncol. 2010;28:4621-4629. Sonneveld P, et al. ASH Annual Meeting Abstracts. 2010;116(21):40. http://web.educationalconcepts.net/Newsletter/MMY015AE1/MMY015AE1.pdf. Accessed July 17, 2012. Moreau P, et al. Blood. 2011;118: 5752-5758.

  8. MPT vs MP in Elderly MM Fayers PM et alBlood.2011;118(5):1239-1247

  9. Overall Survival Median survival: MP 32.7 months (95% CI, 30.5-36.6 months) MPT 39.3 months (95% CI, 35.6-44.6 months). HR 0.83 (95% CI: 0.73-0.94) P=0.004

  10. MPR vs MP in Elderly MM Palumbo et al. N Engl J Med 2012;366:1759-69.

  11. Bortezomib in Transplant Ineligible MM

  12. UPFRONT Study

  13. MM-020: Len + Low-dose Dexvs MPT in Previously Untreated MM • Lenalidomide 25 mg/day, days 1–21, every 28 days • Dexamethasone* 40 mg/day, days 1, 8, 15, 22, every 28 days Until PD • Inclusion criteria • Previously untreated MM • Age  65 years or not a candidate for transplantation • No neuropathy of grade > 2 • CICr > 30 ml/min 18 four-week cycles or until PD • Lenalidomide 25 mg/day, days 1–21, every 28 days • Dexamethasone* 40 mg/day, days 1, 8, 15, 22, every 28 days • 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 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 Protocol CC-5013-MM-020/IFM 07-01. 2007; data on file, Celgene Corporation

  14. 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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