N Engl J Med 2022 Jun 05
Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma.
Abstract
Background
In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown.
Methods
In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival.
Results
Among 357 patients in the RVD-alone group and 365 in the transplantation group, at a median follow-up of 76.0 months, 328 events of disease progression or death occurred; the risk was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% confidence interval [CI], 1.23 to 1.91; P<0.001); median progression-free survival was 46.2 months and 67.5 months. The percentage of patients with a partial response or better was 95.0% in the RVD-alone group and 97.5% in the transplantation group (P = 0.55); 42.0% and 46.8%, respectively, had a complete response or better (P = 0.99). Treatment-related adverse events of grade 3 or higher occurred in 78.2% and 94.2%, respectively; 5-year survival was 79.2% and 80.7% (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65).
Conclusions
Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION ClinicalTrials.gov number, NCT01208662.).
Related Questions
Are you still recommending autologous stem cell transplantation (ASCT) for all eligible myeloma patients who achieve remission after induction with a quadruplet regimen?
Our institution still recommends upfront autologous transplant for most fit patients. We appreciate the recent results from CEPHEUS and BENEFIT, but if we believe that achieving MRD negativity is important, the addition of autologous transplant improves the rate of MRD negativity, which ultimately s...
With the recent approvals of CAR-T for second-line therapy in myeloma, does this change your approach to use of consolidative autologous transplant or autologous transplant as second line therapy?
This is an excellent two-part question, and hopefully one where we'll continue to see more data year by year!The second question (ASCT as second-line therapy) is easier to answer - in brief, I no longer recommend this. Extrapolating from first-line consolidation to second-line salvage ASCT (i.e., f...
What induction regimen do you choose for high risk newly diagnosed multiple myeloma in light of the recent high risk focused studies?
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