Τίτλος:
Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 105 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. Daratumumabassociated infusion-related reactions occurred in 27.7% of the patients. CONCLUSIONS: Among patients with newly diagnosed multiple myeloma who were ineligible for stemcell 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). Copyright © 2017 Massachusetts Medical Society.
Συγγραφείς:
Mateos, M.-V.
Dimopoulos, M.A.
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, A.M.
Campbell, P.
Shelekhova, T.
Yoon, S.-S.
Iosava, G.
Fujisaki, T.
Garg, M.
Chiu, C.
Wang, J.
Carson, R.
Crist, W.
Deraedt, W.
Nguyen, H.
Qi, M.
San-Miguel, J.
Περιοδικό:
The New England journal of medicine
Εκδότης:
Massachussetts Medical Society
Λέξεις-κλειδιά:
bortezomib; daratumumab; melphalan; prednisone; antineoplastic agent; bortezomib; daratumumab; melphalan; monoclonal antibody; prednisone, adult; aged; Article; cancer survival; controlled study; disease severity; drug efficacy; drug safety; drug tolerability; female; follow up; human; major clinical study; multiple cycle treatment; multiple myeloma; neutropenia; outcome assessment; phase 3 clinical trial; priority journal; progression free survival; randomized controlled trial; stem cell transplantation; survival rate; thrombocytopenia; tumor cell; chemically induced; clinical trial; disease free survival; infection; intention to treat analysis; Kaplan Meier method; male; middle aged; mortality; multicenter study; multiple myeloma, Adult; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Disease-Free Survival; Female; Follow-Up Studies; Humans; Infection; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Survival Rate
DOI:
10.1056/NEJMoa1714678
