Background
IFM 2009: phase III RCT randomizing 700 patients ≤65 years with symptomatic newly diagnosed multiple myeloma to RVD induction/consolidation with or without high-dose melphalan plus autologous stem-cell transplantation.
Interventions and follow up
Arm A: RVD Q21D x3 + ASCT, then RVD Q21D x2 consolidation, then lenalidomide maintenance x1yr
Arm B: RVD Q21D x3, then RVD Q21D x5, then lenalidomide maintenance x1yr
Primary endpoint: PFS
mFollow up: 43-44mo
Arm B: RVD Q21D x3, then RVD Q21D x5, then lenalidomide maintenance x1yr
Primary endpoint: PFS
mFollow up: 43-44mo
Results
mPFS: 50mo (Arm A) vs 36mo (Arm B); HR 0.65, 95% CI 0.53–0.80, P<.001
CR rate: 59% vs 48%; P=.03
MRD negativity: 79% vs 65%; P<.001
4yr OS: 81% in both arms (no significant difference)
CR rate: 59% vs 48%; P=.03
MRD negativity: 79% vs 65%; P<.001
4yr OS: 81% in both arms (no significant difference)
Adverse events
Grade ≥3 (Arm A vs B): blood/lymphatic system events 95% vs 64%; GI events 28% vs 7%; infections 20% vs 9%
Second primary cancers: similar between arms (1.5 vs 1.1 invasive cases per 100 patient-years); treatment-related mortality low in both arms
Second primary cancers: similar between arms (1.5 vs 1.1 invasive cases per 100 patient-years); treatment-related mortality low in both arms
Conclusions
In transplant-eligible newly diagnosed MM, RVD induction followed by autologous transplantation improved PFS and depth of response (CR, MRD negativity) over RVD alone, though overall survival was similar. ASCT remains a standard for transplant-eligible patients.
Key Limitations
No OS difference, partly because delayed transplant at relapse was permitted in Arm B. Maintenance limited to 1 year, shorter than current continuous-maintenance standards. Predates routine daratumumab-based induction.
Clinical Context
A pivotal trial supporting upfront ASCT in transplant-eligible NDMM. ESMO and ASCO endorse RVD induction followed by ASCT and lenalidomide maintenance. (Regimens: induction RVD Q21D – lenalidomide 25 mg D1–14, bortezomib 1.3 mg/m2 D1,4,8,11, dexamethasone 20 mg D1,2,4,5,8,9,11,12; consolidation same with reduced dexamethasone 10 mg; maintenance lenalidomide 10 mg, escalated to 15 mg, for 1 year.)
References