Safety of Rapid Daratumumab Infusion: A Retrospective, Multicenter, Real-Life Analysis on 134 Patients With Multiple Myeloma

Abstract

BackgroundThe anti-CD38 monoclonal antibody daratumumab is the backbone of most anti-multiple myeloma (MM) regimens. To mitigate the risk of infusion-related reactions (IRRs), intravenous daratumumab administration requires 7 hours for the first infusion and 3.5-4 hours thereafter, thus making daratumumab-containing regimens burdensome for patients and health care resources. Preliminary data suggest that a rapid (90-minute) infusion of daratumumab is safe and does not increase IRRs. The rapid schedule was adopted by our centers since 2019.MethodsWe conducted an observational multi-center, real-life study to assess the safety of rapid daratumumab infusion protocol from the third administration in relapsed MM patients receiving daratumumab alone or in combination with lenalidomide-dexamethasone or bortezomib-dexamethasone. The primary endpoint was the safety of the rapid infusion protocol, particularly in terms of IRRs.ResultsA total of 134 MM patients were enrolled. IRRs occurred in 7 (5%) patients and were mostly mild (6/7 of grade 1-2), with only 1 patient experiencing a grade 3 IRR. Due to the IRRs, 5 (3.7%) patients discontinued the rapid infusions and resumed daratumumab at the standard infusion rate, while 1 patient permanently discontinued daratumumab. In 4/7 patients (57%), IRRs occurred while resuming rapid daratumumab infusions after a temporary interruption (2-4 months). No other adverse event was considered related to the rapid infusion protocol.ConclusionsOur findings confirmed the safety of rapid daratumumab infusions starting from the third administration. In case of prolonged daratumumab interruption, it is advisable to resume infusions at the standard rate (3.5 hours) before switching to the rapid infusion.

Beyond Clinical Trials in Patients With Multiple Myeloma: A Critical Review of Real-World Results

“…An important issue in the use of daratumumab is the speed of infusion. Indeed, there is RW evidence that a rapid daratumumab infusion protocol did not increase the rate of AEs, as compared with the standard infusion protocol ( 85 , 86 ).…”

New Targeted Agents in Myasthenia Gravis and Future Therapeutic Strategies

“…Drugs targeting the surface proteins of plasma cells constitute yet another therapeutic option. On this basis, various monoclonal antibodies against the glycoprotein CD38 expressed in Ig-secreting plasma cells and thymocytes [ 68 , 69 ] are now being studied for MG. Mezagitamab was recently evaluated in a randomized phase 2 trial, although the results have yet to be published [ 70 ]. Another anti-CD38 antibody, daratumumab, has been evaluated in a retrospective, single-centre case series of seven patients with autoantibody-driven neurological autoimmune diseases, including one patient with MG.…”

Toxicity management strategies for next-generation novel therapeutics in multiple myeloma

“…To decrease infusion times, numerous trials have confirmed that rapid infusion of daratumumab 90 min and isatuximab 70 min can be initiated safely following evidence of tolerability during the first cycle ( Table 3 ). 23 – 29 …”

“…To decrease infusion times, numerous trials have confirmed that rapid infusion of daratumumab 90 min and isatuximab 70 min can be initiated safely following evidence of tolerability during the first cycle (Table 3). [23][24][25][26][27][28][29] Infusion-related reactions (IRRs) are common in all formulations but more likely with IV administration and occur primarily with the first dose (Table 3). Associated symptoms are generally low grade and include chills, fever, nausea, nasal congestion, cough, and dyspnea.…”