Results of an early access treatment protocol of daratumumab in United States patients with relapsed or refractory multiple myeloma

Background Daratumumab is a human CD38-directed monoclonal antibody indicated for the treatment of relapsed and refractory multiple myeloma (MM). Methods A multicenter, open-label treatment protocol provided early access to daratumumab for patients who had progressive MM after they received >= 3 prior lines of therapy that included a proteasome inhibitor and an immunomodulatory agent or if they were refractory to both a proteasome inhibitor and an immunomodulatory agent. Patients received daratumumab 16 mg/kg weekly for 8 weeks, every other week for 16 weeks, and monthly until they developed disease progression, unacceptable toxicity, or 60 days after the drug gained US approval. Treatment-emergent grade >= 3 adverse events (AEs), serious AEs, and AEs of special interest were collected. Results Three hundred forty-eight patients were enrolled at 39 US sites between June and December 2015. Patients received study therapy for a median of 1.9 months (range, 0.03-6.0 months). Fifty-two percent of patients transitioned to commercially-available daratumumab and 37% discontinued because of progressive disease. Grade >= 3 AEs occurred in 50% of patients, including thrombocytopenia (15%) and anemia (14%). Serious AEs occurred in 35% of patients (12% were drug-related), including infections (11%). Infusion reactions occurred in 56%, 2%, and 2% of patients during the first, second, and all subsequent infusions, respectively; respiratory symptoms (cough, dyspnea, throat irritation, nasal congestion) were common. The infusion reaction rate for the first infusion was 38% in 50 patients at 2 sites who received montelukast as premedication for their first infusion and 59% in patients who did not receive montelukast. Conclusions The current findings are consistent with previously reported trials and confirm the safety profile of daratumumab in heavily pretreated US patients who have relapsed or refractory MM. Cancer 2018;124:000-000. (c) 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.