Safety and blood levels of daratumumab after switching from intravenous to subcutaneous administration in patients with multiple myeloma

Abstract

Abstract Purpose: The intravenous administration (IV) of daratumumab sometimes causes an infusion reaction and needs a long infusion time. Recently, a subcutaneous formulation (SC) of daratumumab, which has fewer infusion reactions and shorter administration time, was approved. However, because SC has a fixed dose, overdosing is a concern for patients with low body weights. In this study, we investigated the safety and blood levels of daratumumab after switching from IV to SC in patients with multiple myeloma (MM). Methods: Patients who switched from IV to SC of daratumumab between June 2021 and May 2022 at Kobe City Medical Center General Hospital were included in the study. Blood daratumumab levels were measured using liquid chromatography-tandem mass spectrometry. Safety after switching from IV to SC was evaluated for six months and graded according to the Common Terminology Criteria for Adverse Events, version 5.0. Results: The median body weight of ten patients included in the analysis was 57.4 kg (range: 45.0–74.4). Blood daratumumab levels were significantly increased after switching to SC (p=0.002); median through concentration at the last IV dose was 403.6 µg/mL (range: 96.3–776.3) and that at the third SC dose was 557.1 µg/mL (range: 288.3–997.2). Grade 1–2 injection site reactions were observed in six patients (60.0%) after switching to SC. A new grade 3 adverse event was observed in only one patient (neutropenia). Conclusion:The blood levels of daratumumab were significantly increased after switching from IV to SC in patients with MM; however, the dosage was tolerable.