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AUTOLOGOUS AND ALLOGENEIC TRANSPLANTATION IN MULTIPLE MYELOMA

Vienna, May, 2014 Montserrat Rovira, Laura Rosiñol, Enric Carreras. AUTOLOGOUS AND ALLOGENEIC TRANSPLANTATION IN MULTIPLE MYELOMA. Hospital Clinic, Barcelona. Chemotherapy in Multiple Myeloma. SCT in Multiple Myeloma. HDT/SCT in Primary Refractory Myeloma.

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AUTOLOGOUS AND ALLOGENEIC TRANSPLANTATION IN MULTIPLE MYELOMA

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  1. Vienna, May, 2014 Montserrat Rovira, Laura Rosiñol, Enric Carreras AUTOLOGOUS AND ALLOGENEIC TRANSPLANTATION IN MULTIPLE MYELOMA Hospital Clinic, Barcelona

  2. Chemotherapy in Multiple Myeloma

  3. SCT in Multiple Myeloma

  4. HDT/SCT in Primary Refractory Myeloma * In patients achiving CR after HDT/SCT

  5. Overall Survival: Progressive vs Chemosensitive Disease vs No-change Non-responsive, non-progressive Chemosensitive Progressive disease

  6. SCT in Multiple Myeloma

  7. Higher intensity prior SCT Randomized trials: Single auto-SCT vs. conventional chemotherapy Auto-SCT “Gold-standard” for initial treatment in patients younger than 65 y. Only chemosensitive patients

  8. CR Median not reached Non-CR Median: 60 months OS Probability of SRV according remission after HDT Nadal et al. BMT 2004

  9. CR after HDT According to Tumor Burden Pretransplant *Alexanian et al, BMT 2001; 27: 1037-1043 ** Nadal et al, BMT 2004; 33: 61-64

  10. Which is the best treatment before HSCT?

  11. Treatment options for patients eligible for transplantation Induction Bortezomib-based: VelDex VTD PAD IMiD-based: Thal/Dex TAD CTD Rd VRD ‘Traditional’ VAD CyDex Stem cell harvest High-dose melphalan Stem cell infusion

  12. Pre and Post-ASCT CR Rate with “Novel” Induction Regimens* *Cavo et al, ASH 2009 (abstract 351); Rosiñol et al, ASH 2009 (abstract 130);Harousseau et al, Haematologica 2006; 91: 1498-05; Rosiñol et al, JCO 2007; 25:1498-05; Popat et al, BJH 2008; 141: 512-6; Barlogie et al, BJH 2007; 138:176-85, Roussel et al;Blood 2011; 118(abstract 1872). **VTD-PACE + Tandem ASCT + VTD/TD

  13. SCT in Multiple Myeloma

  14. Single versus Tandem Auto-SCT * CR/VGPR, ** CR/nCR, *** CR, †at 3 years, #In favour of single transplant

  15. IFM 94 : Overall survival P < 0.01 Tandem Single

  16. IFM 94 : OS if response to 1stgraft < 90% P < 0.001 Tandem Single

  17. IFM 94 : OS if response to 1st graft > 90 % P = 0.7 Tandem Single

  18. Single versus Tandem Auto-SCT Problem Many of patient relapsing after single SCT recived a second auto-SCT * CR/VGPR, ** CR/nCR, *** CR, †at 3 years, #In favour of single transplant

  19. SCT in Multiple Myeloma

  20. MM. SYNGENEIC TRANSPLANT“Treatment of Choice” Bensinger et al, BMT 1996 Gahrton et al, BMT 1999

  21. Cy-TBI Mel-TBI Bu-Mel Allogeneic Transplant in MM EBMT 1983  2002 Gahrton G et al. Br J Haematol 2001; 113:209-216. Crawly et al, Blood 2007; 109: 3588-3594

  22. Myeloablative versus Allo-RIC transplantation High TRM: 30-50% High relapse rate: 45% at 3 yrs Cure rate: 10-20% Allo-RIC

  23. Allo-RIC • Conditioning: -- MEL/FLUDA ± ATG or Campath-1H (RIC) -- FLUDA/low dose TBI (non-MAC) • TRM: ≈ 20% (11- 40%) • CR rate: 22-73% • aGVHD: ≈ 40% • cGVHD: 20-45% Usually DLI Included in protocols

  24. Myeloablative versus Allo-RIC transplantation EBMT Experience (1998-2002) Crawley et al, Blood 2007; 109:3588-3594.

  25. Allogeneic Transplant with Dose-Reduced Intensity Conditioning (RIC) • Better results • Chemosensitive disease • Development of GVHD • No ATG or Campath-1H • Previous auto-transplantation

  26. SCT in Multiple Myeloma

  27. Tandem HSCT: ASCT followed by Allo-RIC *TBI 2 Gy +/- Fluda &TBI 2 Gy

  28. Double ASCT versus tandem ASCT/Allo-RIC High Risk Use ATG Allo only if no CR/nCR w auto 13q ATG in UNR Short Follow-up

  29. Patients who completed protocols (58 vs 46 pts) Median follow up: 6 years Auto-Allo Vs Auto-Auto 37 mo. 64 mo. 33 mo. Median Overall Survival Median Event Free Survival Bruno B et al. EBMT Goteborg 2009

  30. Auto/RIC-allo versus Auto in MyelomaProgression Free Survival since 1st transplant Reduction of risk in time: p=0.0012 (Cox) Auto+Allo At 60 mns: 35% (CI: 27% - 45%) Auto only At 60 mns: 18% (CI: 13% - 24%) Auto (N=249) 194 123 96 58 27 8 2 Auto+allo (N=109) 80 57 46 34 19 11 3 Bjorkstrand et al, JCO 2011

  31. Progression-free Survival Overall Survival 100 100 90 90 80 80 70 70 60 60 50 50 40 40 30 30 20 20 10 10 0 0 Survival Outcomes after the First Transplant: Auto-Auto vs. Auto-Allo: Intent-to-treat analysis Krishnan et al Lancet Onc 2011 Auto/Auto, 80% @ 3yr Auto/Auto, 46% @ 3yr Auto/Allo, 77% @ 3yr Probability, % Auto/Allo, 43% @ 3yr p-value = 0.67 p-value = 0.19 Months 0 6 12 18 24 30 36 42 48 # at risk:Auto/Auto 436 395 348 292 242 213 178 54 42Auto/Allo 189 165 138 117 105 89 71 23 16 0 6 12 18 24 30 36 42 48 436 424 406 395 370 348 305 107 79 189 183 167 160 156 143 124 43 27 Mp10_5.ppt

  32. Allo-RIC limitation as first line approach: high TRM • Indications: • High risk patients (cytogenetics, < VGPR?) • First sensible relapse

  33. HSCT in MM: Take-home messages - Auto-HSCT: Standard of care - Allo-RIC after auto: individualize High risk NO YES ? To individualize (+)* YES High risk ? To individualize (-)* Standard risk NO YES Standard risk NO *Age, ISS 3 stage, extramedular afectation, IgD, PCL, MRD (+)

  34. Thanks for your attention

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