Daratumumab successfully treats patients with multiple myeloma who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug (IMiD), or who are double-refractory to those other drugs. However, daratumumab has led to infusion-related reactions in registration studies, including symptoms (cough, wheezing, and rhinorrhea) similar to those of allergic rhinitis. Anecdotal reports indicate that premedication with montelukast, a leukotriene receptor antagonist, may reduce the rate of infusion-related reaction associated with daratumumab therapy.
Chari and colleagues conducted a multicenter, open-label treatment protocol to provide early access to daratumumab and to collect safety data, including infusion-related reactions. Sixty patients received montelukast during therapy, including 50 patients who received montelukast 10 mg given more than 30 minutes prior to the first infusion of daratumumab. The rates of infusion-related reactions at first infusion were 38.0% in those who received montelukast and 58.5% in those who did not. Respiratory symptoms (20% vs 12%) and gastrointestinal symptoms (11% vs 4%) were observed in more patients who did not receive montelukast compared with those who did, respectively. In both groups, chills were observed in 14% of patients.
The median time to infusion was 6.7 hours for patients who received montelukast compared with 7.6 hours for those who did not. Times for the second and subsequent infusions were similar in both groups.
The authors concluded that their findings show that administering montelukast more than 30 minutes prior to the first daratumumab infusion reduced by one-third the rate of infusion-related reactions in patients with multiple myeloma who had received more than 3 prior therapies, including a proteasome inhibitor and an IMiD, or who were double-refractory. The median time for the first infusion was 0.9 hours shorter in patients who received montelukast. Although these findings from this small-scale observational study are promising, the authors acknowledge that additional studies are required to determine whether montelukast mitigates infusion-related reactions associated with the first infusion of daratumumab.
Chari J, et al. ASH 2016. Abstract 2142.
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