1. Addition of daratumumab to bortezomib and dexamethasone increased the rate and length of progression-free survival.
2. The rates of thrombocytopenia and neutropenia had increased in the daratumumab group versus the control group.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Major advances in the treatment of multiple myeloma (MM) have been made through the development of novel agents like proteasome inhibitors such as bortezomib, part of standard regimens for this disease often in combination with glucocorticoids. Another new agent, daratumumab is a human anti-CD38 monoclonal IgG antibody that has been demonstrated to improve the survival of patients with this disease. This study was designed to examine the differences in outcomes for patients with relapsed or refractory MM who were randomly assigned to treatment with either bortezomib and dexamethasone alone or these two agents in combination with daratumumab.
It was found that for the primary end-point, the rate of progression-free survival was significantly higher in the daratumumab group than in the control group. Length of progression-free survival was longer for the daratumumab group versus the control group. The rate of overall response was higher for the daratumumab group than the control group. Nonetheless, the rate of thrombocytopenia and neutropenia were higher in the daratumumab group. This study draws strength from an ideal randomized, controlled design to probe the question of whether the addition of daratumumab is advantageous in refractory or relapsed MM; however, its results are limited by a short follow-up period that prevent examination of overall survival benefit.
Click to read the study, published today in NEJM
Relevant Reading: Impact of novel treatments on multiple myeloma survival
In-Depth [randomized controlled trial]: In this phase 3 trial, 498 patients with refractory or relapsed MM were randomly assigned in a 1:1 ratio to receive daratumumab, bortezomib, and dexamethasone or bortezomib and daratumumab and were followed for a median of 7.4 months. The primary end point of the trial was progression-free survival. Secondary end points included the time to disease progression, the overall response rate, the proportion of patients who achieved very good partial response or better, the duration of response, the time to response, and overall survival. Regarding the primary end-point, progression free survival, the rate of this parameter was 60.7% (95%CI 51.2 to 69.0%) in the daratumumab group versus 26.9% (95%CI 17.1 to 37.5%) in the control group. The twelve-month progression-free survival rate was 77.5% (95%CI 65.2 to 86.0%) in the daratumumab group as compared with 29.4% (95%CI 12.5 to 48.7%) in the control group (HR for progression or death 0.31; 95%CI 0.18 to 0.52; p < 0.001). Overall response was 82.9% in the daratumumab group versus 63.2% in the control group (p < 0.001). Regarding grade three and four toxicities that were recorded, thrombocytopenia was seen in 45.3% of the daratumumab group versus 32.9% in the control group, and neutropenia was seen in 12.8% of the daratumumab group versus 4.2% in the control group.
Image: PD
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