Triplet therapy, transplantation, and maintenance until progression in myeloma Journal Article
| Authors: | Richardson, P. G.; Jacobus, S. J.; Weller, E. A.; Hassoun, H.; Lonial, S.; Raje, N. S.; Medvedova, E.; McCarthy, P. L.; Libby, E. N.; Voorhees, P. M.; Orlowski, R. Z.; Anderson, L. D., Jr.; Zonder, J. A.; Milner, C. P.; Gasparetto, C.; Agha, M. E.; Khan, A. M.; Hurd, D. D.; Gowin, K.; Kamble, R. T.; Jagannath, S.; Nathwani, N.; Alsina, M.; Cornell, R. F.; Hashmi, H.; Campagnaro, E. L.; Andreescu, A. C.; Gentile, T.; Liedtke, M.; Godby, K. N.; Cohen, A. D.; Openshaw, T. H.; Pasquini, M. C.; Giralt, S. A.; Kaufman, J. L.; Yee, A. J.; Scott, E.; Torka, P.; Foley, A.; Fulciniti, M.; Hebert, K.; Samur, M. K.; Masone, K.; Maglio, M. E.; Zeytoonjian, A. A.; Nadeem, O.; Schlossman, R. L.; Laubach, J. P.; Paba-Prada, C.; Ghobrial, I. M.; Perrot, A.; Moreau, P.; Avet-Loiseau, H.; Attal, M.; Anderson, K. C.; Munshi, N. C.; for the DETERMINATION Investigators |
| Article Title: | 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. Copyright © 2022 Massachusetts Medical Society. |
| Keywords: | adult; controlled study; treatment response; aged; disease-free survival; young adult; major clinical study; lenalidomide; clinical trial; fatigue; neutropenia; cancer growth; diarrhea; drug efficacy; drug safety; hypophosphatemia; side effect; treatment duration; disease free survival; drug megadose; follow up; antineoplastic agent; progression free survival; quality of life; bortezomib; multiple cycle treatment; multiple myeloma; sensory neuropathy; anemia; blood toxicity; gastrointestinal symptom; leukopenia; nausea; neuropathy; randomized controlled trial; thrombocytopenia; antineoplastic combined chemotherapy protocols; peripheral neuropathy; maintenance therapy; dexamethasone; melphalan; autologous stem cell transplantation; febrile neutropenia; fever; hyperglycemia; lymphocytopenia; pneumonia; confidence interval; hypokalemia; maculopapular rash; survival time; disease progression; thromboembolism; stem cell mobilization; hazard ratio; phase 3 clinical trial; graft rejection; transplantation, autologous; disease exacerbation; oral mucositis; adverse event; autotransplantation; clinical outcome; hypertransaminasemia; faintness; humans; human; male; female; article; triplet chemotherapy |
| Journal Title: | New England Journal of Medicine |
| Volume: | 387 |
| Issue: | 2 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2022-07-14 |
| Start Page: | 132 |
| End Page: | 147 |
| Language: | English |
| DOI: | 10.1056/NEJMoa2204925 |
| PUBMED: | 35660812 |
| PROVIDER: | scopus |
| PMCID: | PMC10040899 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 August 2022 -- Source: Scopus |
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