DETERMINATION
Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma
Phase 3NCT01208662
- Population
- Adults 18 to 65 years of age with symptomatic multiple myeloma.
- Design
- Phase 3 trial in adults 18 to 65 years of age with symptomatic myeloma who received one cycle of RVD and were then randomly assigned 1:1 to two additional RVD cycles plus stem-cell mobilisation followed by five additional RVD cycles (RVD-alone group), or to high-dose melphalan plus autologous stem-cell transplantation followed by two additional RVD cycles (transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival.
- Primary endpoint
- PFS
- Arms
- RVD alone (control, n = 357): RVD induction and consolidation, then lenalidomide until progression
- RVD plus transplantation (experimental, n = 365): RVD, then high-dose melphalan plus ASCT followed by two RVD cycles, then lenalidomide until progression
- People
- Richardson PG
Δ median PFS+21.3 monthsΔ ORR+2.5 pointsΔ 60-month OS+1.5 points
Show the numbers
| Endpoint | Analysis | RVD plus transplantation | RVD alone | Effect |
|---|---|---|---|---|
| PFSIntention to treat (357 RVD alone, 365 transplantation) | primarymedian follow-up 76 monthsRichardson 2022 | median 67.5 months | median 46.2 months | P<0.001The published hazard ratio is 1.53 (95% CI 1.23 to 1.91): the risk of progression or death was 53% higher in the RVD-alone group than in the transplantation group. It compares RVD alone with transplantation, so it is given here rather than in the structured hazard-ratio field, which is oriented experimental versus control. |
| ORRIntention to treat (357 RVD alone, 365 transplantation)Partial response or better. | primaryRichardson 2022 | 97.5% | 95% | P=0.55Complete response or better 42.0% versus 46.8% (P = 0.99). Treatment-related adverse events of grade 3 or higher 78.2% versus 94.2%. |
| OSIntention to treat (357 RVD alone, 365 transplantation) | primarymedian follow-up 76 monthsRichardson 2022 | 80.7% at 5 y | 79.2% at 5 y | Hazard ratio for death 1.10 (95% CI 0.73 to 1.65) as published; the abstract reports no overall survival benefit with transplantation. |
| Endpoint | Analysis | RVD plus transplantation | RVD alone | Effect |
|---|---|---|---|---|
| PFSIntention to treat (357 RVD alone, 365 transplantation) | primarymedian follow-up 76 monthsRichardson 2022 | median 67.5 months | median 46.2 months | P<0.001The published hazard ratio is 1.53 (95% CI 1.23 to 1.91): the risk of progression or death was 53% higher in the RVD-alone group than in the transplantation group. It compares RVD alone with transplantation, so it is given here rather than in the structured hazard-ratio field, which is oriented experimental versus control. |
| ORRIntention to treat (357 RVD alone, 365 transplantation)Partial response or better. | primaryRichardson 2022 | 97.5% | 95% | P=0.55Complete response or better 42.0% versus 46.8% (P = 0.99). Treatment-related adverse events of grade 3 or higher 78.2% versus 94.2%. |
| OSIntention to treat (357 RVD alone, 365 transplantation) | primarymedian follow-up 76 monthsRichardson 2022 | 80.7% at 5 y | 79.2% at 5 y | Hazard ratio for death 1.10 (95% CI 0.73 to 1.65) as published; the abstract reports no overall survival benefit with transplantation. |
- RVD alone (control)
- RVD plus transplantation (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 transplantation |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 42 | 53.3% | 65.0% |
| 84 | 28.4% | 42.2% |
| 127 | 14.9% | 27.1% |
| 169 | 7.9% | 17.6% |