Work

Dynamics of Infusion-Related Reactions in Patients Treated with Axatilimab for Chronic Graft-Versus-Host Disease in the AGAVE-201 Study

Year: 2026

Type: article

Abstract: Introduction Axatilimab (AXA), a monoclonal antibody targeting colony-stimulating factor 1 receptor, 0.3 mg/kg intravenously every 2 weeks (Q2W) is approved in the US for chronic graft-versus-host disease (cGVHD) after ≥2 lines of systemic therapy based on results from the AGAVE-201 trial (NCT04710576). In AGAVE-201, AXA 0.3 mg/kg Q2W had robust clinical activity and was generally well tolerated. Infusion-related reactions (IRRs) were infrequent but warrant characterization. Objectives To describe the incidence and development of IRRs and the clinical characteristics of patients who had IRRs during AXA treatment in AGAVE-201. Methods In AGAVE-201, patients aged ≥2 years with cGVHD after ≥2 prior lines of therapy received AXA 0.3 mg/kg Q2W, 1 mg/kg Q2W, or 3 mg/kg every 4 weeks (Q4W). Patients were observed for IRRs: for grade 1/2, the infusion rate was decreased by 50% or interrupted until resolution; for grade 3/4, study drug was permanently discontinued. Supportive care was provided per institutional standards. This post hoc analysis included treated patients who had an IRR, reported as ≥1 of the following Medical Dictionary for Regulatory Activities (MedDRA) terms: infusion-related reaction; flushing; hot flush; hypersensitivity; infusion-related hypersensitivity reaction; urticaria; or bronchospasm. The data cutoff was March 30, 2025. Results During AGAVE-201, 23 of 239 patients (9.6%) who received AXA had a total of 38 IRRs, including 11/79 (13.9%), 5/81 (6.2%), and 7/79 (8.9%) patients in the 0.3 mg/kg Q2W, 1 mg/kg Q2W, and 3 mg/kg Q4W dose groups, respectively (Table 1). Concomitant medications were received by 13 patients (56.5%) at the time of the IRR and included glucocorticoids (dexamethasone, hydrocortisone, methylprednisolone, prednisone, or prednisolone; 11 patients [47.8%]), famotidine, topical hydrocortisone (3 patients each [13.0%]), diphenhydramine (2 patients [8.7%]), paracetamol, and topical oral dexamethasone (1 patient each [4.3%]). Terms describing IRRs were infusion-related reaction (n=11 [grade 1, n=5; grade 2, n=6]), urticaria (n=5 [grade 1, n=1; grade 2, n=2; grade 3, n=2]), bronchospasm (n=3 [all grade 2]), flushing (n=3 [all grade 1]), hot flush (n=2 [both grade 1]), hypersensitivity (n=2 [grade 1, n=1; grade 3, n=1]), and infusion-related hypersensitivity reaction (n=1 [grade 2]). Median (range) IRR onset occurred on study day 121 (1–859). Most events (94.7%) resolved with 55.3% resolving on the day of onset. Most patients had mild or moderate IRRs (Table 2). Two patients in the 1 mg/kg Q2W cohort discontinued and 1 patient in the 3 mg/kg Q4W cohort had a dose reduction owing to an IRR. No IRR-related reductions or discontinuations occurred in the 0.3 mg/kg Q2W cohort. Conclusion In AGAVE-201, 9.6% of patients had IRRs during AXA treatment. Most IRRs were mild or moderate and resolved the same day.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.12.403