IFM 2009
Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma
Phase 3N = 700NCT01191060
- Population
- Adults 65 years of age or younger with symptomatic, measurable, newly diagnosed multiple myeloma (full text eligibility criteria); 700 patients were randomised.
- Design
- Randomised trial in 700 patients with multiple myeloma, all given three cycles of RVD induction, then randomly assigned to consolidation with five additional cycles of RVD (350 patients) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (350 patients). Both groups received lenalidomide maintenance for 1 year. The primary end point was progression-free survival.
- Primary endpoint
- PFS
- Arms
- RVD alone (control, n = 350): Three cycles of RVD induction, five additional RVD cycles, then lenalidomide maintenance for 1 year
- RVD plus high-dose melphalan and stem-cell transplant (experimental, n = 350): Three cycles of RVD induction, high-dose melphalan plus stem-cell transplantation, two additional RVD cycles, then lenalidomide maintenance for 1 year
- People
- Attal M
PFSHR 0.65Δ median PFS+14 monthsΔ CR rate+11 pointsΔ MRD+14 pointsΔ 48-month OS−1 points
Show the numbers
| Endpoint | Analysis | RVD plus high-dose melphalan and stem-cell transplant | RVD alone | Effect |
|---|---|---|---|---|
| PFSIntention to treat (700 randomised; stated in the full text) | primaryAttal 2017 | median 50 months | median 36 months | HR 0.65P<0.001Adjusted hazard ratio as published; the abstract does not label its direction, and the transplantation group had the longer median PFS. |
| CR rateIntention to treat (700 randomised; stated in the full text) | primaryAttal 2017 | 59% | 48% | P=0.03 |
| MRDIntention to treat (700 randomised; stated in the full text)Proportion of patients in whom minimal residual disease was not detected. | primaryAttal 2017 | 79% | 65% | P<0.001 |
| OSIntention to treat (700 randomised; stated in the full text) | primaryAttal 2017 | 81% at 4 y | 82% at 4 y | Overall survival at 4 years did not differ significantly. Grade 3 or 4 neutropenia 92% with transplantation versus 47% with RVD alone; gastrointestinal disorders 28% versus 7%; infections 20% versus 9%. |
| Endpoint | Analysis | RVD plus high-dose melphalan and stem-cell transplant | RVD alone | Effect |
|---|---|---|---|---|
| PFSIntention to treat (700 randomised; stated in the full text) | primaryAttal 2017 | median 50 months | median 36 months | HR 0.65P<0.001Adjusted hazard ratio as published; the abstract does not label its direction, and the transplantation group had the longer median PFS. |
| CR rateIntention to treat (700 randomised; stated in the full text) | primaryAttal 2017 | 59% | 48% | P=0.03 |
| MRDIntention to treat (700 randomised; stated in the full text)Proportion of patients in whom minimal residual disease was not detected. | primaryAttal 2017 | 79% | 65% | P<0.001 |
| OSIntention to treat (700 randomised; stated in the full text) | primaryAttal 2017 | 81% at 4 y | 82% at 4 y | Overall survival at 4 years did not differ significantly. Grade 3 or 4 neutropenia 92% with transplantation versus 47% with RVD alone; gastrointestinal disorders 28% versus 7%; infections 20% versus 9%. |
- RVD alone (control)
- RVD plus high-dose melphalan and stem-cell transplant (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | RVD alone | RVD plus high-dose melphalan and stem-cell transplant |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 31 | 55.1% | 65.1% |
| 63 | 29.7% | 41.8% |
| 94 | 16.4% | 27.2% |
| 125 | 9.0% | 17.7% |