MULTIPLE MYELOMA : RAVI VIJ

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  • Trends in Overall Survival of MMKumar et al studied survival in 387 patients who were treated at the Mayo Clinic from 1971–2006 and experienced a first relapse after ASCTPatients were divided into 2 cohorts, those with a relapse date on or before December 31, 2000 and those with a later relapse date Median overall survival (OS) was longer for patients who relapsed after 2000 compared with those who relapsed prior to this date (23.9 vs 11.8 months)Improved outcome of patients with MM has been observed in recent years, both in the relapsed setting as well as at diagnosisReferenceKumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and theimpact of novel therapies. Blood. 2008;111(5):2516-2520.
  • CR associated with OS prolongation in post-induction and post-transplant settingsAssessing the prognostic impact of achieving CR has been difficultbecause of the use of different definitions of CR.1 [Harousseau/p3139/c2/para3/lines1-3]Although not all studies show a correlation between CR and OS in MM, CR generally indicates patients who are likely to live longer.2 [Wang/p500/fig1]Many studies have demonstrated that CR is usually associated with longer overall survival.1[Harousseau/p3140/c2/para1/lines1-9]These findings have been demonstrated in both the postinduction and posttransplant settings.3[Lahuerta/p5778/table3]1. Harousseau J-L et al. Blood. 2009;114(15):3139-3146. 2. Wang M et al. Bone Marrow Transplant. 2010;45(3):498-504.3. Lahuerta JJ et al. J Clin Oncol. 2008;26(35):5775-5782.
  • MULTIPLE MYELOMA : RAVI VIJ

    1. 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. 2. Trends in Overall Survival of MM Overall survival 1971–2006 Diagnosis period Median OS 1996–2006 45 months 1971–1996 30 months (P<0.001) Kumar SK, et al. Blood. 2008;111:2516-2520. Time from diagnosis (Months) Survival 0 0.2 0.4 0.6 0.8 1.0 0 20 40 60 80 100 120 140 2001–2006 1995–2000 2001–2006 1989–1994 1983–1988 1977–1982 1971–1976 OS, overall survival. 2 M
    3. 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. 4. CR associated with OS prolongation in post- induction and post-transplant settings1-3 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. 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. 5. > 65 yrs > 75 yrs Importance of CR in Elderly MM Gay F et al. Blood. 2011;117(11):3025-3031)
    6. 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. 7. Bortezomib-Based Induction Prior to SCT Trial Regimen N CR+VGPR Post- Induction (%) CR+VGPR Post-ASCT (%) PFS P Value Cavo et al, 2010 VTD vs TD 236 238 62* 28 82* 64 68% at 3 yr 56% at 3 yr .0057 Moreau et al, 2011 IFM 2007/02 VD vs vTD 99 100 36 49‡ 58 74§ 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;376:2075-2085. Harousseau JL, et al. J Clin Oncol. 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. 8. Fayers PM et alBlood.2011;118(5):1239-1247 MPT vs MP in Elderly MM
    9. 9. 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 Overall Survival
    10. 10. Palumbo et al. N Engl J Med 2012;366:1759-69. MPR vs MP in Elderly MM
    11. 11. Study Regimen N ORR CR/nCR Outcomes VISTA San Miguel et al. Mateos et al. Phase III VMP MP 344 338 71% 35% 33% 4% 5 yr OS: 46% 5 yr OS: 34.4% UPFRONT Niesvizky et al. Phase III VMP/Vel VTD/Vel VD/Vel 300 73% 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. 12. UPFRONT Study
    13. 13. MM-020: Len + Low-dose Dex vs MPT in Previously Untreated MM Protocol CC-5013-MM-020/IFM 07-01. 2007; data on file, Celgene Corporation Inclusion criteria •Previously untreated MM •Age 65 years or not a candidate for transplantation •No neuropathy of grade > 2 •CICr > 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
    14. 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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