Daratumumab, bortezomib, and dexamethasone for multiple myeloma

Antonio Palumbo, Asher A Chanan Khan, Katja Weisel, Ajay K. Nooka, Tamas Masszi, Meral Beksac, Ivan Spicka, Vania Hungria, Markus Munder, Maria V. Mateos, Tomer M. Mark, Ming Qi, Jordan Schecter, Himal Amin, Xiang Qin, William Deraedt, Tahamtan Ahmadi, Andrew Spencer, Pieter Sonneveld

Research output: Contribution to journalArticle

477 Citations (Scopus)

Abstract

BACKGROUND: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival. RESULTS: A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group. After a median follow-up period of 7.4 months, the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95% confidence interval, 0.28 to 0.53; P<0.001). The rate of overall response was higher in the daratumumab group than in the control group (82.9% vs. 63.2%, P<0.001), as were the rates of very good partial response or better (59.2% vs. 29.1%, P<0.001) and complete response or better (19.2% vs. 9.0%, P = 0.001). Three of the most common grade 3 or 4 adverse events reported in the daratumumab group and the control group were thrombocytopenia (45.3% and 32.9%, respectively), anemia (14.4% and 16.0%, respectively), and neutropenia (12.8% and 4.2%, respectively). Infusion-related reactions that were associated with daratumumab treatment were reported in 45.3% of the patients in the daratumumab group; these reactions were mostly grade 1 or 2 (grade 3 in 8.6% of the patients), and in 98.2% of these patients, they occurred during the first infusion. CONCLUSIONS: Among patients with relapsed or relapsed and refractory multiple myeloma, daratumumab in combination with bortezomib and dexamethasone resulted in significantly longer progression-free survival than bortezomib and dexamethasone alone and was associated with infusion-related reactions and higher rates of thrombocytopenia and neutropenia than bortezomib and dexamethasone alone.

Original languageEnglish (US)
Pages (from-to)754-766
Number of pages13
JournalNew England Journal of Medicine
Volume375
Issue number8
DOIs
StatePublished - Aug 25 2016

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Multiple Myeloma
Dexamethasone
Disease-Free Survival
Control Groups
Neutropenia
Thrombocytopenia
daratumumab
Bortezomib
Body Surface Area
Anemia
Immunoglobulin G
Monoclonal Antibodies
Body Weight
Confidence Intervals

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Palumbo, A., Chanan Khan, A. A., Weisel, K., Nooka, A. K., Masszi, T., Beksac, M., ... Sonneveld, P. (2016). Daratumumab, bortezomib, and dexamethasone for multiple myeloma. New England Journal of Medicine, 375(8), 754-766. https://doi.org/10.1056/NEJMoa1606038

Daratumumab, bortezomib, and dexamethasone for multiple myeloma. / Palumbo, Antonio; Chanan Khan, Asher A; Weisel, Katja; Nooka, Ajay K.; Masszi, Tamas; Beksac, Meral; Spicka, Ivan; Hungria, Vania; Munder, Markus; Mateos, Maria V.; Mark, Tomer M.; Qi, Ming; Schecter, Jordan; Amin, Himal; Qin, Xiang; Deraedt, William; Ahmadi, Tahamtan; Spencer, Andrew; Sonneveld, Pieter.

In: New England Journal of Medicine, Vol. 375, No. 8, 25.08.2016, p. 754-766.

Research output: Contribution to journalArticle

Palumbo, A, Chanan Khan, AA, Weisel, K, Nooka, AK, Masszi, T, Beksac, M, Spicka, I, Hungria, V, Munder, M, Mateos, MV, Mark, TM, Qi, M, Schecter, J, Amin, H, Qin, X, Deraedt, W, Ahmadi, T, Spencer, A & Sonneveld, P 2016, 'Daratumumab, bortezomib, and dexamethasone for multiple myeloma', New England Journal of Medicine, vol. 375, no. 8, pp. 754-766. https://doi.org/10.1056/NEJMoa1606038
Palumbo, Antonio ; Chanan Khan, Asher A ; Weisel, Katja ; Nooka, Ajay K. ; Masszi, Tamas ; Beksac, Meral ; Spicka, Ivan ; Hungria, Vania ; Munder, Markus ; Mateos, Maria V. ; Mark, Tomer M. ; Qi, Ming ; Schecter, Jordan ; Amin, Himal ; Qin, Xiang ; Deraedt, William ; Ahmadi, Tahamtan ; Spencer, Andrew ; Sonneveld, Pieter. / Daratumumab, bortezomib, and dexamethasone for multiple myeloma. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 8. pp. 754-766.
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abstract = "BACKGROUND: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival. RESULTS: A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7{\%} in the daratumumab group versus 26.9{\%} in the control group. After a median follow-up period of 7.4 months, the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95{\%} confidence interval, 0.28 to 0.53; P<0.001). The rate of overall response was higher in the daratumumab group than in the control group (82.9{\%} vs. 63.2{\%}, P<0.001), as were the rates of very good partial response or better (59.2{\%} vs. 29.1{\%}, P<0.001) and complete response or better (19.2{\%} vs. 9.0{\%}, P = 0.001). Three of the most common grade 3 or 4 adverse events reported in the daratumumab group and the control group were thrombocytopenia (45.3{\%} and 32.9{\%}, respectively), anemia (14.4{\%} and 16.0{\%}, respectively), and neutropenia (12.8{\%} and 4.2{\%}, respectively). Infusion-related reactions that were associated with daratumumab treatment were reported in 45.3{\%} of the patients in the daratumumab group; these reactions were mostly grade 1 or 2 (grade 3 in 8.6{\%} of the patients), and in 98.2{\%} of these patients, they occurred during the first infusion. CONCLUSIONS: Among patients with relapsed or relapsed and refractory multiple myeloma, daratumumab in combination with bortezomib and dexamethasone resulted in significantly longer progression-free survival than bortezomib and dexamethasone alone and was associated with infusion-related reactions and higher rates of thrombocytopenia and neutropenia than bortezomib and dexamethasone alone.",
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TY - JOUR

T1 - Daratumumab, bortezomib, and dexamethasone for multiple myeloma

AU - Palumbo, Antonio

AU - Chanan Khan, Asher A

AU - Weisel, Katja

AU - Nooka, Ajay K.

AU - Masszi, Tamas

AU - Beksac, Meral

AU - Spicka, Ivan

AU - Hungria, Vania

AU - Munder, Markus

AU - Mateos, Maria V.

AU - Mark, Tomer M.

AU - Qi, Ming

AU - Schecter, Jordan

AU - Amin, Himal

AU - Qin, Xiang

AU - Deraedt, William

AU - Ahmadi, Tahamtan

AU - Spencer, Andrew

AU - Sonneveld, Pieter

PY - 2016/8/25

Y1 - 2016/8/25

N2 - BACKGROUND: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival. RESULTS: A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group. After a median follow-up period of 7.4 months, the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95% confidence interval, 0.28 to 0.53; P<0.001). The rate of overall response was higher in the daratumumab group than in the control group (82.9% vs. 63.2%, P<0.001), as were the rates of very good partial response or better (59.2% vs. 29.1%, P<0.001) and complete response or better (19.2% vs. 9.0%, P = 0.001). Three of the most common grade 3 or 4 adverse events reported in the daratumumab group and the control group were thrombocytopenia (45.3% and 32.9%, respectively), anemia (14.4% and 16.0%, respectively), and neutropenia (12.8% and 4.2%, respectively). Infusion-related reactions that were associated with daratumumab treatment were reported in 45.3% of the patients in the daratumumab group; these reactions were mostly grade 1 or 2 (grade 3 in 8.6% of the patients), and in 98.2% of these patients, they occurred during the first infusion. CONCLUSIONS: Among patients with relapsed or relapsed and refractory multiple myeloma, daratumumab in combination with bortezomib and dexamethasone resulted in significantly longer progression-free survival than bortezomib and dexamethasone alone and was associated with infusion-related reactions and higher rates of thrombocytopenia and neutropenia than bortezomib and dexamethasone alone.

AB - BACKGROUND: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival. RESULTS: A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group. After a median follow-up period of 7.4 months, the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95% confidence interval, 0.28 to 0.53; P<0.001). The rate of overall response was higher in the daratumumab group than in the control group (82.9% vs. 63.2%, P<0.001), as were the rates of very good partial response or better (59.2% vs. 29.1%, P<0.001) and complete response or better (19.2% vs. 9.0%, P = 0.001). Three of the most common grade 3 or 4 adverse events reported in the daratumumab group and the control group were thrombocytopenia (45.3% and 32.9%, respectively), anemia (14.4% and 16.0%, respectively), and neutropenia (12.8% and 4.2%, respectively). Infusion-related reactions that were associated with daratumumab treatment were reported in 45.3% of the patients in the daratumumab group; these reactions were mostly grade 1 or 2 (grade 3 in 8.6% of the patients), and in 98.2% of these patients, they occurred during the first infusion. CONCLUSIONS: Among patients with relapsed or relapsed and refractory multiple myeloma, daratumumab in combination with bortezomib and dexamethasone resulted in significantly longer progression-free survival than bortezomib and dexamethasone alone and was associated with infusion-related reactions and higher rates of thrombocytopenia and neutropenia than bortezomib and dexamethasone alone.

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