In a retrospective analysis published in JCO Oncology Practice, Smolders et al investigated the incidence and clinical course of infusion-related reactions among patients treated with at least one monoclonal antibody in routine practice. The study evaluated real-world data to compare observed infusion-related reaction incidence with reported clinical trial rates and to assess whether patients were able to safely continue monoclonal antibody therapy after an adverse event.
Study Details
The study was conducted at a large tertiary hospital and included patients treated with one or more of 10 selected monoclonal antibodies (atezolizumab, bevacizumab, durvalumab, ipilimumab, nivolumab, panitumumab, pembrolizumab, trastuzumab, pertuzumab, and rituximab). Patient data were drawn retrospectively from electronic medical records between January 2021 and June 2022, enabling the investigators to perform a systematic review of all adverse events and infusion notes. Patients already exposed to the same monoclonal antibody before 2021 or treated within clinical trials were excluded, but those previously treated with other monoclonal antibodies were eligible. After a consensus was reached as to which events could be classified as infusion-related reactions, they were graded using the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
Key Results
Among the 692 patients included in the analysis, 47 (6.7%) experienced at least one infusion-related reaction, totaling 64 events. Most infusion-related reactions (53%) occurred during the first administration, 28% occurred during the second, and fewer than 20% occurred during subsequent cycles. Most reactions were mild to moderate (grade 1 or 2), with five grade 3 events observed across the cohort. All patients were able to safely continue treatment following appropriate management, which typically involved pausing infusion and restarting at a reduced rate, with or without supportive medications.
Infusion-related reactions most often presented as chills, fever, back pain, rash, or gastrointestinal discomfort. Interventions such as corticosteroids, acetaminophen, and antihistamines were variably employed, especially in patients receiving rituximab. One patient discontinued monoclonal antibody therapy entirely after repeated reactions, but this was attributed partly to frailty and ongoing treatment response rather than the severity of the infusion reaction.
The incidence of infusion-related reactions varied substantially by drug. Rituximab accounted for the majority of cases, with 26% of patients (35 of 134) experiencing at least one reaction, mostly during the first infusion. This rate is slightly lower than the literature range of 23%–77% (10% of which were reported as severe). Ipilimumab plus nivolumab was associated with a 13% incidence of infusion-related reactions, primarily attributed to nivolumab (9%). This exceeds the 2.2% to 4% rate reported in prior studies, noted the investigators. In contrast, trastuzumab plus pertuzumab was associated with four infusion-related reactions (3.8%), markedly lower than the 16% to 45% typically reported. During the study period, no infusion-related reactions were recorded for atezolizumab, bevacizumab, durvalumab, nivolumab monotherapy, panitumumab, and pembrolizumab.
The authors emphasized that although rituximab remains the most common agent associated with infusion-related reactions, and nivolumab given in combination with ipilimumab showed a higher-than-expected incidence, the overall real-world frequency of infusion-related reactions was relatively low. “When [infusion-related reactions] are adequately recognized and managed, all patients can safely continue with [monoclonal antibodies],” they concluded.
Elise J. Smolders, PhD, PharmD, of the Department of Clinical Pharmacy, Isala Hospital, Zwolle, the Netherlands, is the corresponding author of the Journal of Clinical Oncology Practice article.
Disclosure: The study was funded by the Isala Science and Innovation Fund. For full disclosures of all study authors, visit ascopubs.org.
