Consolidation after Autologous Stem Cell Transplantion Joan Bladé Laura Rosiñol Department of Hematology Hospital Clínic de Barcelona Berlin, September 11 th 2011
Autologous Stem Cell Transplant in Younger Patients with MM Old approach CR rate: 35% Median OS: 6 years Cure fraction: 10%
Autologous transplantation Greatest Benefit TTP according to response to transplant (CR vs. PR) 1,0 0,9 0,8 Cumulative Proportion Surviving 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0-0,1 CR No CR 0 2 4 6 8 10 12 14 16 18 Years Rovira et al. EBMT 2009 (abstract P592)
Autologous transplantation Greatest Benefit Overall survival according response to transplant (CR vs. PR) 1,0 0,9 Cumulative Proportion Surviving 0,8 0,7 0,6 0,5 0,4 0,3 0,2 No CR CR 0,1 0,0 0 2 4 6 8 10 12 14 16 18 Years Rovira et al. EBMT 2009 (abstract P592)
Barlogie et al. Br J Haematol 2006 Total Therapy
Best treatment for younger patients Refined Total Therapy
Refined Total Therapy
Refined Total Therapy Triple induction regimen ASCT Consolidation Maintenance VTD? MEL-200 VRD? Len+glucocorticoids ±bortezomib
Autologous transplantation Up-front therapy Pre and Post-ASCT CR Rate with Novel Regimens* Regimen Pre-ASCT Post-ASCT Thal/Dex 6% 23-34% Vel/Dex 11% 31% PAD-1 24% 43% VTD 21-30% 43-52% Total Therapy III** - 56% at 2 yrs **VTD-PACE + Tandem ASCT + VTD/TD *Cavo et al, Lancet 2010; Rosiñol et al, ASH 2010; 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.
Best High-dose Therapy Regimen MEL-200 MEL-200 / Bortezomib * MEL-140 / Busulfan ** * Roussel et al, Blood 2010 ** Lahuerta et al, Haematologica 2010
Total Therapy I, II and III Importance of not only achieving but sustaining CR* * Hoering et al, Blood 2009
Impact of MRD on CR duration Multiparameter flow cytometry* Molecular studies** * Paiva et al. Blood 2008 ** Ladetto et al. JCO 2010
Post-ASCT Consolidation Concept Short period of therapy 2 6 months? Longer? Full drug dosing Aim Further decrease tumor burden
Autologous transplantation Consolidation therapy Bortezomib (x 6 cycles) Increase the postrasplant CR/nCR Lenalidomide (x 2 cycles) Improved postrasplant response Mellqvist et al, ASH 2009 (abstract 530) Attal et al, ASH 2009 (abstract 529)
Autologous transplantation Consolidation therapy 39 patients in CR or VGPR post-asct Consolidation with 4 cycles of VTD Follow-up with RT-PCR Median follow-up: 32 months Complete molecular remission (n=6) Very low molecular tumor burden (N=19) High molecular tumor burden (n=13) Continued remissions 3 relapses 11 Relapses MRD (-) correlates with a very low probability of relapse Ladetto et al, JCO 2010
Autologous transplantation Consolidation therapy Bortezomib as single agent 299 patients 21-week consolidation during 3-8 months CR/nCR: Bortezomib vs. No consolidation At randomization: 23% vs. 21% 9 months after ASCT: 54% vs. 35% Upgrade response: 20% vs. 12% Relapses: 1% vs. 6% Mellqvist et al, ASH 2010 (abstract 530)
Autologous transplantation Consolidation therapy Bortezomib, thalidomide and dexamethasone (vtd) 46 eligible patients (induction VD 82%, vtd 11%) Response improvement: 39% CR change rate after consolidation: 23% to 36% No toxic death or grade 3/4 hematological toxicities Roussel et al, ASH 2010 (abstract 3041)
Autologous transplantation Consolidation therapy Bortezomib, thalidomide and dexamethasone (VTD) versus Thalidomide-Dexamethasone (TD) after double ASCT: Phase 3 study VTD significantly superior to TD in consolidation CR rate: 60% vs. 44% Upgrade response: 55% vs. 37% Median PFS: Not reached vs. 42 motnhs No difference in OS Cavo et al, ASH 2010 (abstract 42)
Autologous transplantation Consolidation therapy Bortezomib, thalidomide and dexamethasone (VTD) versus Thalidomide-Dexamethasone (TD) after double ASCT: Molecular MRD assessment 67 eligible patients in CR or ncr Quantitative PCR analysis TD: median 1 log reduction VTD: median 5 log reduction Terragna et al, ASH 2010 (abstract 861)
Autologous transplantation Consolidation therapy Bortezomib, lenalidomide and dexamethasone (VRD) 31 patients evaluable Two 21-day consolidation cycles CR rate: After induction: 28% After ASCT: 35% After consolidation: 52% Roussel et al, ASH 2010 (abstract 624)
Refined Total Therapy Triple induction regimen ASCT Consolidation Maintenance