MULTIPLE MYELOMA RISK STRATIFICATION

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MULTIPLE MYELOMA RISK STRATIFICATION

  1. 1. Education Clinical Care Research Multiple Myeloma: Risk Stratified Treatment Strategies A/Prof Chng Wee Joo Head, Haematologic Malignancies Department of Haematology-Oncology National Cancer Institute of Singapore National University Health System Deputy Director and Senior Principle Investigator Cancer Science Institute, Singapore National University of Singapore
  2. 2. International Staging System Greipp et al JCO 2005;23:3142
  3. 3. Genetic Abnormalities Detected by FISH Abnormalities Frequencies Prognosis t(4;14) 10-15% Poor t(11;14) 15-20% Neutral t(14;16) 3-5% Poor 1q21 Gain 30-35% Poor 13q14 del 45-50% Neutral 17p13 del 5-10% Poor
  4. 4. Summary of Prognostic Factors Pre-treatment Post-treatment Host Age Albumin Tumor Burden MRI/PET-CT Durie-Salmon Beta-2 microglobulin MRI/PET-CT Tumor Biology PCLI Genetics Response
  5. 5. Prognostic impact of t(4;14)/del(17p) with ISS 4-year Deaths/N estimate a ISS I or ISS II and Normal FISH 193/610 76% (72,79) b ISS I and Abnormal FISH/ISS III and Normal FISH 140/252 52% (45,58) c ISS II or ISS III and Abnormal FISH 146/196 32% (26,39) Avet-loiseau et al. ASH 2009
  6. 6. JCO 2012 epub
  7. 7. Can novel agents modulate risk?
  8. 8. A1 A2 B1 B2 Induction Consolidation HDT with Mel200 & ASCT VAD x 4 VAD x 4 Vel-Dex x 4 Vel-Dex x 4 DCEP x 2 DCEP x 2 JCO 2010; 28; 4630-4634
  9. 9. t(4;14) with Velcade® treatment VAD Vel/Dex pvalue (logrank) Patients 98 106 0.0006Relapses 82 43 Median EFS (years) [IC 95%] 1.36 [1.08 ; 1.56] 2.32 [1.49 ; 2.95] p=.0006 Vel/Dex VADp=.0006 Vel/Dex VAD p=.0004 treatment VAD Vel/Dex pvalue (logrank) Patients 106 107 0.0004Deaths 70 20 Median OS (years) [IC 95%] 2.87 [1.76 ; 3.48] ---* [3.60 ; -- -*] EFS OS
  10. 10. t(4;14) with Velcade® t(4 ;14) neg pos pvalue (logrank) Patients 396 106 0.0178Relapses 141 43 Median EFS (years) [IC 95%] 2.90 [2.74 ; 3.53] 2.32 [1.49 ; 2.95] p<.02 t(4;14) pos t(4;14) neg t(4;14) neg t(4;14) pos p=.002 t(4 ;14) neg pos pvalue (logrank) Patients 400 107 0.0020Deaths 38 20 Median OS (years) [IC 95%] ---* [---* ; ---*] ---* [3.60 ; --- *] EFS OS
  11. 11. Del(17p) with Velcade® treatment VAD Vel/Dex pvalue (logrank) Patients 101 50 0.3156Relapses 82 30 Median EFS (years) [IC 95%] 1.47 [1.17 ; 1.83] 1.17 [0.72 ; 2.01] Vel/Dex VAD p=.32 Vel/Dex VAD p=.49 treatment VAD Vel/Dex pvalue (logrank) Patients 115 51 0.4857Deaths 70 15 Median OS (years) [IC 95%] 2.40 [1.83 ; 3.66] 4.07 [3.10 ; -- -*]
  12. 12. Del(17p) with Velcade® Del(17p) > 60% pvalue (logrank) Patients 475 50 < 0.0001Relapses 166 30 Median EFS (years) [IC 95%] 2.95 [2.75 ; 3.71] 1.17 [0.72 ; 2.01] p<.0001 Del(17p) pos No del(17p) No del(17p) Del(17p) pos p<.0001 Del(17p) > 60% pvalue (logrank) Patients 480 51 < 0.0001Deaths 48 15 Median OS (years) [IC 95%] ---* [---* ; ---*] 4.07 [3.10 ; -- -*] EFS OS
  13. 13. Lancet 2010; 376: 2075-2085
  14. 14. Shaughnesy et al. Br J Haematol 2009; 147:347-351
  15. 15. Risk Stratification
  16. 16. What have we learn • Velcade especially benefit t(4;14) patients • Inclusion of Velcade (and hence prolonged use) in different phases of treatment is important in high-risk disease • The use of double autologous transplant seem to also be an important factor. • Revlimid seem to have a more moderate and less consistent effect on high-risk disease • Thalidomide maintenance contra-indicated in 17p13 deletion
  17. 17. How do I apply Risk Stratification in Clinic for transplant eligible patients? • Induction – Velcade triplet for everyone if can afford – If cannot afford • Velcade triplet for intermediate and high-risk disease • CTD for standard and low-risk disease. If not VGPR by 4 cycles, to then change to velcade triplet
  18. 18. How do I apply Risk Stratification in Clinic for transplant eligible patients? • ASCT Consolidation – Double (Mel200) autologous SCT for intermediate and high-risk disease – Single transplant (Mel200) for others – If did not have Velcade at induction, consider incorporating velcade to Mel200 conditioning
  19. 19. • Post-ASCT Consolidation – If low or standard-risk, no consolidation if achieve VGPR – If intermediate or high-risk, 2 cycle of Velcade triplet consolidation regardless of response • Maintenance – If low-risk, no maintenance if achieve VGPR – If standard-risk, Rev maintenance – If intermediate or high-risk, Velcade maintenance How do I apply Risk Stratification in Clinic for transplant eligible patients?
  20. 20. Risk Stratification - Questions
  21. 21. Copyright © 2008 National University Health System Thank you for your attention

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