Successful use of split-dose intravenous daratumumab in a multiple myeloma patient after a first-dose life-threatening infusion-related reaction

Abstract

Introduction Daratumumab is a humanized IgG1 kappa monoclonal antibody directed against CD38 used to treat myeloma. The recommended dose of daratumumab is 16 mg/kg, with no lower or upper threshold. Here, we present the first split-dose daratumumab infusion experience in a myeloma patient with morbid obesity in whom daratumumab was interrupted because of grade 3 infusion-related reaction. Case report A female myeloma patient with morbid obesity received a combination of chemotherapy with daratumumab because of disease relapse. The calculated dose for the first intravenous daratumumab infusion was 1840 mg/day based on the weight of the patient, which was measured as 115 kilograms. Daratumumab infusion was initiated as appropriate but needed to be stopped because of a severe sudden presentation of shortness of breath and hypoxemia. Management and outcome After daratumumab was stopped, premedication was repeated, and oxygen, intravenous and inhaler steroids, inhaler β2 agonists and intravenous diphenhydramine were given in repeated doses. She was monitored and followed up in the emergency critical care unit. Daratumumab treatment with a split-dose schedule was planned after she fully recovered from all signs and symptoms. The total dose was divided into two doses and was given without any complications on two consecutive days. After that, she was also able to tolerate once a week 1840 mg of daratumumab in a single day. Discussion There is a paucity of data regarding the best practice for instituting intravenous daratumumab in patients with morbid obesity regarding the infusion rate and duration, optimal dosing, and ideal way to cope with infusion-related reactions. Our case suggests a potential role for a split-dose schedule for patients with obesity and potential dose reductions and infusion-related reactions.