Overcome Daratumumab’ severe reaction with desensitization in relapsed multiple myeloma

Abstract

Introduction

Daratumumab, a monoclonal antibody that specifically targets the myeloma cells’ CD38 antigen, is promisingly used in both monotherapy and combination therapy for relapsed patients with multiple myeloma. However, this approach had a significant challenge due to the high rate of infusion-related reaction in the first dosage (up to 38%) despite strict instructions on infusion rate and dilution volume. This study describes a patient who overcame severe infusion reaction after the first dosage by desensitization.

Case report

A 60-year-old man with multiple myeloma was relapsed with multiple bone damage and elevated immunoglobulin D lambda after VTD (bortezomid, thalidomide, dexamethasone) regimen completion. After 60 min of initial Daratumumab dose with sufficient pre-medication, the patient manifested suspected grade 3 infustion reaction and was transported to the intensive care unit.

Management and outcome

Daratumumab was immediately terminated; adrenaline, methylprednisolone, and diphenhydramine were started. Another regimen was performed. However, due to substantial progression of symptoms, a re-introduction of daratumumab was considered. Daratumumab prick and intradermal skin test was performed with negative result. Desensitization were sucessfull with the number of bags and steps gradually lowered with no adverse events observed. After three cycles, the patient achieved VGPR (Very Good Partial Response) without any symptomatic spinal cord compression.

Conclusion

Desensitization is a promising solution to overcome daratumumab's severe infusion reaction, opening the new approach for clinicians. To ensure success, it is important to have a multidisciplinary team with experienced allergist, hematologist, Intensive Care Init (ICU) team and oncology pharmacist to create a safe environment for desensitization.