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A Single Center Retrospective Evaluation of Daratumumab Infusion Related Reactions with Split-First Dose Day 1 and Day 2 Infusion


 Introduction:
 Monoclonal antibody's infusion related reactions (IRRs) include anaphylaxis, anaphylactoid reactions and cytokine release syndrome. These reactions are related to the time of infusion. Incidence of IRRs in patients treated with daratumumab is reported to be about 42%. Severity of the most commonly reported IRRs, during the first dose of infusion are between grade I and II. Approved dosage of daratumumab is 16 mg/kg IV weekly given for 1 through 8 weeks, then every 2 weeks from 9th through 24th week, after which it is given every 4 weeks from 25th week onwards, its use is continued until disease progression. The goal of this study is to evaluate the IRRs at cycle 1 day 1 (C1D1) and C1D2, using split dose daratumumab (8 mg/kg) and to look for the impact of prior leukotriene receptor antagonist administration on the incidence of IRRs.
 Methods:
 To study the IRRs at day 1 using split dose daratumumab C1D1 (8 mg/kg) and C1D2 (8 mg/kg), we performed a retrospective review of medical records of relapsed/refractory (R/R) multiple myeloma patients receiving daratumumab between December 1st, 2015 to March 31st, 2018 at our center. Key variables related to each patient were recorded from Epic electronic database. Data were summarized using counts and percentages.
 Results:
 A total of 35 patients were included and the incidence of IRRs was measured. Overall, 13 (37.14%) patients developed IRRs on day 1. Out of these 13 patients, 11 (84.61%) patients had grade II IRRs, 1 (7.69%) patient had grade I IRRs and 1 (7.69%) patient had grade III IRRs.
 Nineteen (54.2%) patients out of a total 35 patients were pretreated with montelukast; out of these 19 patients, 5 (26.31%) patients had grade II IRRs and 1 (5.26%) patient had grade III IRRs. Thus, 31.57% patients had IRRs with montelukast pretreatment. No patient had grade I or grade IV IRRs.
 Sixteen (45.71%) patients out of total 35 patients were not pretreated with Montelukast; out of these 16 patients, 6 (37.5%) patients had grade II IRRs and 1 (6.25%) patient had grade I IRR. No patient had grade III or grade IV IRR. Thus, 43.75% patients had IRRs without montelukast. Overall, 12.18% reduction in IRRs was noted with pretreatment using montelukast.
 Conclusion:
 This single center study demonstrates that split dose model of daratumumab in the treatment of R/R multiple myeloma shows lower incidence of IRRs when compared to historical controls reported in the literature. Moreover, pretreatment with leukotriene receptor antagonist also appear to decreases the incidence of IRRs in our patient population. Future randomized prospective trials are needed to support these findings and improving the overall impact on tolerance for daratumumab.
 
 
 
 No relevant conflicts of interest to declare.
