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

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. To describe the incidence and development of IRRs and the clinical characteristics of patients who had IRRs during AXA treatment in AGAVE-201. 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. 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. In AGAVE-201, 9.6% of patients had IRRs during AXA treatment. Most IRRs were mild or moderate and resolved the same day.