Daratumumab desensitization: Novel approaches in POEMS syndrome experience

Daratumumab is a human IgG1κ monoclonal antibody targeting CD38, with infusion-related reactions occurring in 45–48% of patients. Among these, 5–10% are severe, requiring treatment discontinuation in 1% of cases. The incidence of hypersensitivity reactions (HSRs) to daratumumab is unknown. We describe a 37-year-old male diagnosed with POEMS syndrome and treated with autologous hematopoietic stem cell transplantation and chemotherapy. Presenting a relapse of the disease, intravenous daratumumab was initiated. Ten minutes after starting the first infusion, he presented with generalized rash, abdominal pain, vomiting, pharyngeal pruritus, throat tightness, dyspnea, decreased oxygen saturation, tachycardia and diaphoresis (Brown III). Due to the refractory disease and lack of alternatives, a desensitization protocol for daratumumab 1000 mg was implemented using a (3 bag-12 step) over 5.67 h. Eight successful desensitizations were performed without hypersensitivity reactions, enabling safe drug reintroduction. Currently, only one successful daratumumab desensitization protocol has been published, involving a 4-bag, 14-step procedure over 5.2 h, as reported by Carrón-Herrero et al. Prior to desensitization, the patient experienced flushing, pharyngeal pruritus, bronchospasm, dyspnea, desaturation, bradycardia, and hypotension. Both case reports were associated with severe anaphylaxis, ultimately enabling the safe reintroduction of the drug.