A systematic review and meta-analysis of 5 phase 3 randomized controlled trials (RCTs) revealed that patients receiving daratumumab-containing regimens were significantly less likely to discontinue treatment due to adverse events (AEs) than those in the comparator group.
Daratumumab is a human, CD38-targeting, immunoglobulin G subclass 1 κ light chain monoclonal antibody with direct antitumor effects and an immunomodulatory component that has recently led to survival improvements in patients with multiple myeloma (MM). However, safety concerns with daratumumab are considerable.
To determine the risk for treatment delay and treatment-related deaths in patients with MM treated with daratumumab, the study investigators conducted a comprehensive literature search using the MEDLINE® and Embase databases, along with meeting abstracts from inception through June 2019. Five large phase 3 RCTs with a total of 3547 patients with MM were eligible. The randomization ratio was 1:1 in all studies.
Daratumumab was used as first-line treatment for patients with MM in the ALCYONE study, the CASSIOPEIA study, and the MAIA study. Patients in these studies received bortezomib, melphalan, and prednisone, either alone or with daratumumab (n = 700); bortezomib, thalidomide, and dexamethasone alone or in combination with daratumumab (n = 1085); or lenalidomide and dexamethasone alone or in combination with daratumumab (n = 737), respectively.
Daratumumab was utilized in relapsed and refractory MM in the POLLUX study, which randomized 564 patients to receive lenalidomide and dexamethasone either alone or in combination with daratumumab, and in the CASTOR study, which assigned 480 patients to receive bortezomib and dexamethasone alone or in combination with daratumumab.
Treatment delays due to AEs were noted in 120 (6.77%) patients in the collective daratumumab group, compared with 179 (10.08%) in the control group. Treatment delay due to infection or pneumonia was reported in 0.8% of daratumumab patients versus 0.45% in the control group, but this was not a statistically significant difference (P = 0.49), the investigators noted. Treatment-related deaths were 64 (3.61%) in the daratumumab arm and 77 (4.34%) in the control arm.
“The rate of discontinuation of trial treatment due to adverse events was significantly lower in the daratumumab group (6.77%) than in the control arm (10.08%), with a risk ratio of 0.68 favoring the daratumumab combination regimen,” said presenting author Thura Win Htut, of Aberdeen Royal Infirmary Hospital in Aberdeen, United Kingdom. “Furthermore, there was no significant difference in treatment discontinuation due to pneumonia or infection, or in treatment-related deaths due to treatment-related adverse events in the daratumumab group compared to the control arm.”
Htut TW, et al. ASH Abstract 1873. Session 653.
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