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. 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.

Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma / 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.; Foa, R.. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - 378:6(2018), pp. 518-528. [10.1056/NEJMoa1714678]

Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma

Foa R.
2018

Abstract

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. 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.
2018
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; Medicine (all)
01 Pubblicazione su rivista::01a Articolo in rivista
Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma / 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.; Foa, R.. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - 378:6(2018), pp. 518-528. [10.1056/NEJMoa1714678]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1085850
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