KEY TAKEAWAYS
- The phase 3 (DFCI 10-106) trial evaluated the efficacy of ASCT in combination with RVD compared to standard RVD therapy alone in adults with newly diagnosed multiple myeloma.
- The study involved administering a single cycle of RVD to all participants, followed by either continued standard RVD therapy or ASCT and two more cycles of RVD.
- The study’s outcome showed that the group receiving ASCT had significantly longer median progression-free survival than the group receiving standard RVD therapy alone.
- The study found that both groups had similar rates of partial response or better, but the transplantation group had a slightly higher rate of complete reaction or better.
- ASCT, in combination with RVD therapy followed by lenalidomide maintenance therapy, can improve progression-free survival in adults with multiple myeloma compared to RVD therapy alone.
Autologous stem cell transplantation (ASCT) combined with standard triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, has not been studied in patients with newly diagnosed multiple myeloma. Adults with symptomatic myeloma (aged 18 to 65) participated in a phase 3 trial where they were given a single cycle of RVD. These patients were split into two groups: those who would continue with standard RVD treatment after two more cycles plus stem-cell mobilization (the RVD-alone group) and those who would undergo autologous stem-cell transplantation followed by two more RVD cycles (the transplantation group). Lenalidomide was given to both groups indefinitely or until the disease progressed too far or the side effects became intolerable. Progression-free survival was the critical measure of success.
Median progression-free survival was 46.2 months and 67.5 months, respectively, for the 357 patients in the RVD-alone group and the 365 patients in the transplantation group, at a median follow-up of 76.0 months. The risk of disease progression or death was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% CI, 1.23 to 1.91; P<0.001). 95.0% of patients in the RVD-alone group and 97.5% of patients in the transplantation group had a partial response or better (P = 0.55); 42.0% and 46.8% of patients in the RVD-alone and transplantation groups, respectively, had a complete response or better (P = 0.99). Overall, 79.2% and 80.7% of patients survived 5 years after treatment (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65) despite experiencing grade 3 or higher treatment-related adverse events in 78.2% and 94.2%, respectively. Treatment with RVD plus ASCT, as opposed to RVD alone, improved progression-free survival in adults with multiple myeloma. There was no improvement in overall survival.
Source:https://pubmed.ncbi.nlm.nih.gov/35660812/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT01208662
Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, Medvedova E, McCarthy PL, Libby EN, Voorhees PM, Orlowski RZ, Anderson LD Jr, Zonder JA, Milner CP, Gasparetto C, Agha ME, Khan AM, Hurd DD, Gowin K, Kamble RT, Jagannath S, Nathwani N, Alsina M, Cornell RF, Hashmi H, Campagnaro EL, Andreescu AC, Gentile T, Liedtke M, Godby KN, Cohen AD, Openshaw TH, Pasquini MC, Giralt SA, Kaufman JL, Yee AJ, Scott E, Torka P, Foley A, Fulciniti M, Hebert K, Samur MK, Masone K, Maglio ME, Zeytoonjian AA, Nadeem O, Schlossman RL, Laubach JP, Paba-Prada C, Ghobrial IM, Perrot A, Moreau P, Avet-Loiseau H, Attal M, Anderson KC, Munshi NC; DETERMINATION Investigators. Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. N Engl J Med. 2022 Jul 14;387(2):132-147. doi: 10.1056/NEJMoa2204925. Epub 2022 Jun 5. PMID: 35660812; PMCID: PMC10040899.
