|Title||Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Richardson, PG, Jacobus, SJ, Weller, EA, Hassoun, H, Lonial, S, Raje, NS, Medvedova, E, McCarthy, PL, Libby, EN, Voorhees, PM, Orlowski, RZ, Anderson, LD, Zonder, JA, Milner, CP, Gasparetto, C, Agha, ME, Khan, AM, Hurd, DD, Gowin, K, Kamble, RT, Jagannath, S, Nathwani, N, Alsina, M, R Cornell, F, 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|
|Corporate Authors||DETERMINATION Investigators|
|Journal||N Engl J Med|
|Date Published||2022 07 14|
|Keywords||Adult, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Bortezomib, Dexamethasone, Disease Progression, Disease-Free Survival, Humans, Lenalidomide, Maintenance Chemotherapy, Melphalan, Multiple Myeloma, Stem Cell Transplantation, Transplantation, Autologous|
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.).
|Alternate Journal||N Engl J Med|
|Grant List||N/a / / Takeda Pharmaceuticals North America / |
Grants P01-155258 and 5P50 CA100707 (PGR, MKS, HA- / NH / NIH HHS / United States
U01 HL069294 / HL / NHLBI NIH HHS / United States
U10HL069294 to the Blood and Marrow Transplant Cli / HL / NHLBI NIH HHS / United States
U24HL138660 to the Blood and Marrow Transplant Cli / CA / NCI NIH HHS / United States
N/a / / Celgene /