Daratumumab monotherapy showed encouraging efficacy in heavily pretreated and refractory patients with multiple myeloma and had a favorable safety profile in this patient population, a study published in the journal The Lancet has shown.1

Because new treatment options are needed for patients with multiple myeloma that are refractory to proteasome inhibitors and immunomodulatory agents, researchers sought to assess daratumumab, a novel targeted monoclonal antibody, in patients with refractory disease.

For the international, open-label, phase 3 trial, researchers enrolled 106 patients with multiple myeloma who were previously treated with at least 3 lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or who were refractory to both drugs. Patients received daratumumab 16 mg/kg intravenously weekly for 8 weeks, then every 2 weeks for 16 weeks, followed by every 4 weeks thereafter.

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Results showed that the overall response rate was 29.2% (95% CI, 20.8 – 38.9). Three patients achieved a stringent complete response, 10 had a very good partial response, and 18 had a partial response. Researchers found that the median time to first response was 1.0 month and the median duration of response was 7.4 months (95% CI, 5.5 – not estimable).

Median progression-free survival and overall survival were 3.7 months (95% CI, 2.8 – 4.6) and 17.5 months (95% CI, 13.7 – not estimable), respectively.

In terms of safety, the investigators determined that daratumumab was well tolerated, with fatigue and anemia being the most common adverse events. Of note, no daratumumab-related adverse events resulted in discontinuation of treatment.

Daratumumab was recently approved by the U.S. Food and Drug Administration for the treatment of patients with multiple myeloma who have received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent. Approval was based on the aforementioned study under accelerated approval based on response rate.


  1. Lonial S, Weiss BM, Usmani S, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial [published online ahead of print January 6, 2016]. Lancet. doi: 10.1016/S0140-6736(15)01120-4.