Predictors of response and safety profile of axatilimab in chronic GVHD: Pooled analysis of 384 patients.

Abstract

e18564 Background: Chronic graft-versus-host disease (cGVHD) remains a significant complication following allogeneic hematopoietic cell transplantation, impacting more than half of HCT recipients. Monocytes and macrophages dependent on colony-stimulating factor 1 receptor (CSF1R) play a crucial role as mediators in chronic GVHD. Axatilimab, a humanized monoclonal antibody, blocks CSF-1R signaling to inhibit macrophage development and has demonstrated promising clinical benefits in chronic GVHD. We conducted a systematic review and meta-analysis to synthesize the available clinical evidence on axatilimab’s efficacy and safety in cGVHD. Methods: We followed PRISMA guidelines to search major databases until December 2025 for studies on axatilimab in chronic graft-versus-host disease (cGVHD), including clinical trials and cohorts. Two reviewers independently screened studies, extracted data, and assessed bias using the ROBINS-I, RoB 2.0, and NOS tools. Pooled proportions were calculated with random-effects models in R (R Foundation for Statistical Computing, Vienna, Austria) using the meta package. A p-value of less than 0.05 was considered statistically significant. Results: A total of five studies comprising 384 patients were included in the meta-analysis. Using a random-effects model, the pooled overall response rate across all studies was 73% (95% CI: 60%–82%) (p<0.05). Organ-specific analyses demonstrated variable clinically significant response rates. The pooled response rate was 19% (95% CI: 4%–54%) for ocular involvement, 25% (95% CI: 6%–63%) for pulmonary involvement, 52% (95% CI: 33%–71%) for oral cavity involvement, and 42% (95% CI: 8%–86%) for joint/fascial involvement. Higher response rates were observed in gastrointestinal manifestations (p>0.05), with pooled estimates of 79% (95% CI: 7%–99%) for esophageal involvement, 99% (95% CI: 1%–100%) for lower gastrointestinal involvement, and 97% (95% CI: 0%–100%) for upper gastrointestinal involvement. It was noted that any grade treatment-related adverse events occurred in 96% of participants (95% CI: 39%–100%). The wide confidence intervals reflect the limited sample size of the studies. Conclusions: In conclusion, axatilimab demonstrates promising efficacy in treating chronic graft-versus-host disease (cGVHD), achieving an overall response rate of 73%. Response rates varied by organ involvement, with particularly high rates in gastrointestinal manifestations. However, treatment-related adverse events were noted in 96% of patients, emphasizing the need for careful monitoring. Due to the limited sample sizes and wide confidence intervals, further research is warranted to better understand the risk-benefit profile of axatilimab for the management of cGVHD.