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| PMID: | 29231133 |
| Autor: | Mateos MV; Dimopoulos MA; Cavo M; Suzuki K; Jakubowiak A; Knop S; Doyen C; Lucio P; Nagy Z; Kaplan P; Pour L; Cook M; Grosicki S; Crepaldi A; Liberati AM; Campbell P; Shelekhova T; Yoon SS; Iosava G; Fujisaki T; Garg M; Chiu C; Wang J; Carson R; Crist W; Deraedt W; Nguyen H; Qi M; San-Miguel J; ALCYONE Trial Investigators | | Endereço: | From University Hospital of Salamanca-Instituto de Investigación Biomédica de Salamanca, Salamanca (M.-V.M.), and Clínica Universidad de Navarra-Centro de Investigación Médica Aplicada, Instituto de Investigación Sanitaria de Navarra, Centro de Investigación Biomédica en Red de Cáncer, Pamplona (J.S |
| Título: | Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. |
| Fonte: | N Engl J Med; 378(6):518-528, 2018 02 08. |
| ISSN: | 1533-4406 | | País de publicação: | United States |
| Idioma: | eng | | Resumo: | BACKGROUND: The combination of bortezomib, melphalan, and prednisone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. Daratumumab has shown efficacy in combination with standard-of-care regimens in patients with relapsed or refractory multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 706 patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation to receive nine cycles of bortezomib, melphalan, and prednisone either alone (control group) or with daratumumab (daratumumab group) until disease progression. The primary end point was progression-free survival. RESULTS: At a median follow-up of 16.5 months in a prespecified interim analysis, the 18-month progression-free survival rate was 71.6% (95% confidence interval [CI], 65.5 to 76.8) in the daratumumab group and 50.2% (95% CI, 43.2 to 56.7) in the control group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The overall response rate was 90.9% in the daratumumab group, as compared with 73.9% in the control group (P<0.001), and the rate of complete response or better (including stringent complete response) was 42.6%, versus 24.4% (P<0.001). In the daratumumab group, 22.3% of the patients were negative for minimal residual disease (at a threshold of 1 tumor cell per 10 white cells), as compared with 6.2% of those in the control group (P<0.001). The most common adverse events of grade 3 or 4 were hematologic: neutropenia (in 39.9% of the patients in the daratumumab group and in 38.7% of those in the control group), thrombocytopenia (in 34.4% and 37.6%, respectively), and anemia (in 15.9% and 19.8%, respectively). The rate of grade 3 or 4 infections was 23.1% in the daratumumab group and 14.7% in the control group; the rate of treatment discontinuation due to infections was 0.9% and 1.4%, respectively. Daratumumab-associated infusion-related reactions occurred in 27.7% of the patients. CONCLUSIONS: Among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, daratumumab combined with bortezomib, melphalan, and prednisone resulted in a lower risk of disease progression or death than the same regimen without daratumumab. The daratumumab-containing regimen was associated with more grade 3 or 4 infections. (Funded by Janssen Research and Development; ALCYONE ClinicalTrials.gov number, NCT02195479 .). |
| Tipo de publicação: | CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T |
| Nome de substância: | 0 (Antibodies, Monoclonal); 4Z63YK6E0E (daratumumab); 69G8BD63PP (Bortezomib); Q41OR9510P (Melphalan); VB0R961HZT (Prednisone) |
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