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

Abstract

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.

Ninety-minute daratumumab infusion is safe in multiple myeloma

“…To decrease the IRR rate, one trial tested the addition of 10 mg of montelukast as a premedication prior to the first daratumumab infusion and found the IRR rate was one-third lower in patients who received this leukotriene inhibitor[8]. Beyond slowing the infusion rate, no other clinical trial has successfully reported any intervention to decrease the IRR rate[9].…”

Daratumumab in multiple myeloma

“…For patients experiencing IRs, the infusion should be held and can be restarted at the starting infusion rate after the IR has subsided and the patients’ symptoms have resolved or returned to the baseline . Our institutional experience led to the inclusion of 10 mg of oral montelukast in our protocol as a pre‐infusion medication for the first dose of daratumumab administration . No dose reductions are needed for daratumumab during rechallenging for the next cycle.…”

Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses

“…Finally, Chari et al reported safety results from a multicenter, open-label treatment protocol providing early access to daratumumab for US patients who had RRMM after ≥3 prior lines of therapy that included a PI and an IMID or who were double refractory [21]. Three hundred forty-eight patients were enrolled and received daratumumab for a median of 1.9 months (range, 0.03-6 months).…”