FDA Approval Summary: Daratumumab for Treatment of Multiple Myeloma After One Prior Therapy

Abstract

On November 21, 2016, the U.S. Food and Drug Administration granted regular approval to daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on two randomized, open-label trials in which daratumumab was added to these backbone therapies. The MMY3003 trial demonstrated substantial improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone. The estimated median PFS had not been reached in the daratumumab arm and was 18.4 months in the control arm (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: 0.27-0.52; p < .0001), representing a 63% reduction in the risk of disease progression or death. Similar results were observed in the MMY3004 trial comparing the combination of daratumumab, bortezomib, and dexamethasone with bortezomib and dexamethasone. The estimated median PFS was not reached in the daratumumab arm and was 7.2 months in the control arm (HR = 0.39; 95% CI: 0.28-0.53; p < .0001), representing a 61% reduction in the risk of disease progression or death. The most frequently reported adverse reactions (greater than or equal to 20%) in MMY3003 were infusion reactions, diarrhea, nausea, fatigue, pyrexia, upper respiratory tract infection, muscle spasm, cough, and dyspnea. The most frequently reported adverse reactions (greater than or equal to 20%) in MMY3004 were infusion reactions, diarrhea, peripheral edema, upper respiratory tract infection, and peripheral sensory neuropathy. Neutropenia and thrombocytopenia have been added to the Warnings and Precautions of the drug label.

Implications for practice: Daratumumab, the first monoclonal antibody targeted against CD38, received U.S. Food and Drug Administration accelerated approval in 2015 based on data from single-agent, single-arm trials that provided response rate information. Results of the MMY3003 and MMY3004 trials established that daratumumab can be combined synergistically with some of the most highly active agents used to treat multiple myeloma, leading to daratumumab's regular approval in 2016. Daratumumab added to lenalidomide and dexamethasone, or bortezomib and dexamethasone, provides a substantial improvement in progression-free survival in previously treated patients with multiple myeloma. These combinations will likely improve the survival outlook for patients with multiple myeloma.

Keywords: Daratumumab; Multiple myeloma.

Figure 1.

Progression‐free survival Kaplan‐Meier plot for study MMY3003. Abbreviations: DRd, daratumumab added to lenalidomide and dexamethasone; Rd, lenalidomide and dexamethasone.

Figure 2.

Study MMY3003 Kaplan‐Meier plot for overall survival. Abbreviations: DRd, daratumumab added to lenalidomide and dexamethasone; Rd, lenalidomide and dexamethasone.

Figure 3.

Progression‐free survival Kaplan‐Meier plot for study MMY3004. Abbreviations: DVd, daratumumab added to bortezomib and dexamethasone; Vd, bortezomib and dexamethasone.

Figure 4.

Study MMY3004 Kaplan‐Meier plot of overall survival. Abbreviations: DVd, daratumumab added to bortezomib and dexamethasone; Vd, bortezomib and dexamethasone.