Transplant in MM patients: Early versus late. Mario Boccadoro. Barcelona

Transcription

1 Transplant in MM patients: Early versus late Barcelona Mario Boccadoro DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY

2 Transplant in MM patients: Early versus late favorable results shown by multi-drug inductions, consolidations, and long-term maintenance approaches have challenged the role of ASCT (Palumbo A and Cavallo F, Prepublished online June 22, 2012)

3 Transplant in MM patients: Early versus late favorable results shown by multi-drug inductions, consolidations, and long-term maintenance approaches have challenged the role of ASCT (Palumbo A and Cavallo F, Prepublished online June 22, 2012) MPR vs Mel 200

4 GIMEMA: Italian Multiple Myeloma Network MELPHALAN/PREDNISONE/LENALIDOMIDE (MPR) VERSUS HIGH-DOSE MELPHALAN (200 mg/m 2 ) AND AUTOLOGOUS TRANSPLANTATION (MEL200) IN NEWLY DIAGNOSED MULTIPLE MYELOMA (MM) PATIENTS: A PHASE III TRIAL Federica Cavallo, Barbara Lupo, Francesco Di Raimondo, Dina Ben Yehuda, Paolo Corradini, Francesca Patriarca, Michele Cavo, Angelo Michele Carella, Paola Omedè, Anfisa Stanevsky, Agostina Siniscalchi, Maide Cavalli, Magda Marcatti, D Petrò, Claudia Crippa, Anna Levi, Tommaso Caravita Di Toritto, Arnon Nagler, Mario Boccadoro, Antonio Palumbo

5 AIMS Comparison between: Conventional chemo incorporating new drugs ASCT incorporating new drugs Early versus late ASCT ASCT: autologous stem cell transplantation

6 Treatment schedule 402 patients (younger than 65 years) randomized from 62 centers Patients: Symptomatic disease, organ damage, measurable disease Rd* four 28-day courses R: 25 mg/d, days 1-21 d: 40 mg/d, days 1,8,15,22 1 R A N D O M I Z A T I O N MPR six 28-day courses M: 0.18 mg/kg/d, days 1-4 P: 2 mg/kg/d, days 1-4 R: 10 mg/d, days 1-21 MEL200 two courses M: 200 mg/m2 day -2 Stem cell support day 0 2 R A N D O M I Z A T I O N NO MAINTENANCE MAINTENANCE 28-day courses until relapse R: 10 mg/day, days 1-21 *Thromboprophylaxis randomization: aspirin vs low molecular weight heparin R, lenalidomide; d, low-dose dexamethasone; M, melphalan; P, prednisone; MEL200, melphalan 200 mg/m 2

7 Patient Characteristics MPR MEL200 (N=202) (N=200) Age (median) < 55 years years > 60 years 58 33% 29% 38% 58 40% 23% 37% ISS Stage I / II / III, (%) 47 / 30 / / 29 / 24 Chromosome abnormalities t(4;14) t(14;16) Del 17 NA 16% 6% 17% 25% 13% 4% 13% 31% MPR, melphalan-prednisone-lenalidomide; MEL200, melphalan 200 mg/m 2 ; ISS, International Staging System; NA, not available

8 Best response rate MPR (N=130) MEL200 (N=143) P value CR 20% 25% 0.55 > VGPR 60% 62% 0.80 > PR 95% 96% Patients (%) MPR Patients (%) MEL CR VGPR PR SD PD CR VGPR PR SD PD MPR, melphalan-prednisone-lenalidomide; MEL200, melphalan 200 mg/m 2 ; CR, complete response; VGPR, very good partial response; PR, partial response; SD, stable disease; PD, progressive disease

9 Progression Free Survival 45% Reduced Risk of Progression Median follow-up 38 months 3-years PFS Median PFS 1.00 MEL200 60% Not reached MPR 36% months Patients (%) HR 0.55 P < Months MPR, melphalan-prednisone-lenalidomide; MEL200, melphalan 200 mg/m 2 ; PFS, progression free survival; HR, hazard ratio

10 Overall Survival Median follow-up 38 months 3-years OS 1.00 MEL200 MPR 80% 79% Patients (%) HR P = Months MPR, melphalan-prednisone-lenalidomide; MEL200, melphalan 200 mg/m 2 ; OS, overall survival; HR, hazard ratio

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12 MPR versus MEL200

13 Transplant in MM patients: Early versus late favorable results shown by multi-drug inductions, consolidations, and long-term maintenance approaches have challenged the role of ASCT (Palumbo A and Cavallo F, Prepublished online June 22, 2012) MPR vs Mel 200 PFS Mel 200 > MPR PFS Mel 200 > MPR low risk MPR less toxic than Mel 200 OS Mel 200 = MPR

14 Transplant in MM patients: Early versus late favorable results shown by multi-drug inductions, consolidations, and long-term maintenance approaches have challenged the role of ASCT (Palumbo A and Cavallo F, Prepublished online June 22, 2012) MPR vs Mel 200 PFS Mel 200 > MPR PFS Mel 200 > MPR low risk MPR less toxic than Mel 200 OS Mel 200 = MPR 2 large randomized European trials

15 A randomized phase III study to compare VMP with MEL-200 followed by VRD consolidation and lenalidomide maintenance in newly diagnosed multiple myeloma patients

16 A randomized phase III study to compare bortezomib, melphalan, prednisone (VMP) with high-dose melphalan followed by bortezomib, lenalidomide, dexamethasone (VRD) consolidation and lenalidomide maintenance in patients with newly diagnosed multiple myeloma INDUCTION 1500 pts 3 VCD + CY 4 VMP (500 pts) 1 HDM (500 pts) 2 HDM (500 pts) NONE VRD NONE VRD NONE VRD Maintenance Maintenance Maintenance HDM at 1 relapse

17 Aims To investigate what is the best treatment for younger patients with symptomatic MM in a organized way Specific questions Is HDM + ASCT plus novel agents in first line better than MP based regimen + novel agents What is the benefit of 1 vs 2 HDM Is consolidation combined with maintenance treatment better than maintenance alone Is HDM + ASCT plus novel agents in first line better than in first relapse

18 IFM 2009/DFCI trial design N = 886 RVD 3 Stem cell collection RVD 5 MEL200 + ASCT RVD 2 Lenalidomide Lenalidomide 1 year 1 year HDM + ASCT at relapse HDM = high-dose melphalan. Major question: can early SCT prolong the EFS?

19 Partitioned Kaplan-Meier survival curves according to treatment group, ie, early HDT group (top plot) and late HDT group (bottom plot). Fermand J et al. Blood 1998;92: by American Society of Hematology

20 Transplant in MM patients: Early versus late favorable results shown by multi-drug inductions, consolidations, and long-term maintenance approaches have challenged the role of ASCT (Palumbo A and Cavallo F, Prepublished online June 22, 2012) MPR vs Mel 200 PFS Mel 200 > MPR PFS Mel 200 > MPR low risk MPR less toxic than Mel 200 OS Mel 200 = MPR 2 large randomized European trials Conclusions: Wait for the results Toxicities, QoL, and pronostic factors will play a major role

21 Early versus late efficacy toxicyty - EFS, OS -TWISST time without symptoms and treatment toxicity - hematological toxicity - non-hematological toxicity DIVISIONE UNIVERSITARIA DI EMATOLOGIA AZIENDA OSPEDALIERA SAN GIOVANNI TORINO, ITALY