Daratumumab therapy is successful in patients with multiple myeloma who have received ≥3 previous lines of therapy, including a proteasome inhibitor and an immunomodulatory drug (IMiD), or whose disease is double-refractory to those other drugs. However, daratumumab has led to infusion-related reactions in clinical trials, including symptoms (eg, cough, wheezing, rhinorrhea) that are associated with 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.
Investigators used a multicenter, open-label treatment protocol to provide early access to daratumumab and to collect safety data, including infusion-related reactions. In this study, 60 patients received montelukast during multiple myeloma therapy, including 50 patients who received montelukast 10 mg >30 minutes before the first infusion of daratumumab. Infusion-related reactions at first infusion were 38.0% with montelukast and 58.5% without it.
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. Chills were seen in 14% of patients in each group.
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.
According to the investigators, these findings show that administering montelukast >30 minutes before the first infusion with daratumumab reduced the rate of infusion-related reactions by approximately 33% in patients who had received >3 previous therapies, including a proteasome inhibitor and an IMiD, or whose disease was double-refractory to those agents. The median time for the first infusion was 0.9 hours shorter in patients who received montelukast.
Although the 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.