Axatilimab Immunogenicity and Clinical Relevance in Patients with Chronic Graft-Versus-Host Disease.

Axatilimab, a monoclonal antibody targeting colony-stimulating factor 1 (CSF-1) receptor, is approved in the US for the treatment of chronic graft-versus-host disease (cGVHD) after failure of ≥2 lines of systemic therapy. In this study, the effects of antidrug antibody (ADA) status on the pharmacokinetics, pharmacodynamics, efficacy, and safety of axatilimab were evaluated. Among the 319 assessable participants, including 276 participants with cGVHD, 109 (34.2%) were treatment-emergent ADA-positive, with ADA onset occurring within the first month of treatment for 60.8% of treatment-induced ADA-positive participants. Among the 93 patients with cGVHD and treatment-emergent ADAs, 47 (50.5%) patients were neutralizing antibody (NAb)-positive, with NAb onset mostly occurring within the first 6 months of treatment. Samples that were ADA-negative were generally associated with higher axatilimab trough concentrations compared with ADA-positive samples, especially at later time points. Changes in CSF-1 based on ADA status were consistent with changes in axatilimab exposure. In contrast, nonclassical monocyte levels were similar regardless of ADA or NAb status, suggesting that immunogenicity did not affect nonclassical monocytic cell concentrations. No differences in overall response, ≥7-point improvement in modified Lee Symptom Scale responses, or duration of response were observed between the different ADA and NAb subgroups. The incidence of safety events was generally consistent across ADA and NAb subgroups. In conclusion, no meaningful differences in pharmacokinetics, pharmacodynamics, efficacy, and safety were observed between subgroups of axatilimab-treated participants with different ADA statuses. These results suggest that the development of ADAs and NAbs should not affect treatment decisions with axatilimab.