Axatilimab Displays Durable Responses in cGVHD Irrespective of Number of Prior Lines of Treatment

Treatment with the novel colony-stimulating factor 1 (CSF-1R)–blocking antibody axatilimab (Niktimvo) was effective in terms of overall response rate (ORR) in patients with chronic graft-versus-host disease (cGVHD) regardless of the number of prior lines of therapy (LOT) received, according to findings from a post-hoc analysis of the phase 1 AGAVE-201 trial (NCT04710576) presented during the 2025 Transplantation and Cellular Therapy Meetings.1

In particular, patients who received axatilimab immediately after a regimen of ruxolitinib (Rituxan) demonstrated rapid and durable clinical responses, according to a poster presented by Carrie Kitko, MD, and colleagues. Kitko is an associate professor of pediatrics, Hematology/Oncology; the holder of the Ingram Professorship in Pediatric Oncology, Department of Pediatrics; and the medical director of the Pediatric Stem Cell Transplantation Program, at Vanderbilt University Medical Center in Nashville, Tennessee.

For all doses of axatilimab (n = 241), ORRs were similar for patients whose best response to their last prior treatment was a complete response (CR) or partial response (PR; n = 82), no change (n = 116), and disease progression (n = 16), at respective rates of 64.6% (95% CI, 53.3%-74.9%), 62.1% (95% CI, 52.6%-70.9%), and 62.5% (95% CI, 35.4%-84.8%). Investigators noted a slight increase in ORRs among patients who received a greater number of LOT. Among patients who received 2 LOT (n = 35), the ORR was 51.4% (95% CI, 34.0%-68.6%); for 3 LOT (n = 49), the ORR was 61.2% (95% CI, 46.2%-74.8%), and for 4 LOT (n = 49), the ORR was 63.3% (95% CI, 48.3%-76.6%).

For patients who received 0.3 mg/kg of axatilimab, ORR for a CR or PR (n = 30) was 63.3% (95% CI, 43.9%-80.1%), no change (n = 32) was 81.3% (95% CI, 63.6%-92.8%), and disease progression (n = 6) was 83.3% (95% CI, 35.9%-99.6%). Among patients who received this same dosage, those with 2 LOT (n = 11) had an ORR of 63.6% (95% CI, 30.8%-89.1%), 3 LOT (n = 15) had an ORR of 53.3% (95% CI, 26.6%-78.7%), and 4 LOT (n = 17) had an ORR of 82.4% (95% CI, 68.6%-90.7%).

In patients who received rituximab in the last line of therapy across all doses of axatilimab (n = 68), the ORR was 61.8% (95% CI, 49.2%-73.3%), with a median time to response (TTR) of 1.9 months (range, 0.9-5.8) and a sustained response rate (SRR) of 43.0% (95% CI, 31%-55%). For patients who received belumosudil in the last line of therapy (n = 34), the ORR was 50.0% (95% CI, 32.4%-67.6%), the median TTR was 1.9 months (range, 0.9-3.9), and the SRR was 26.0% (95% CI, 13%-44%).

Organ-specific responses to axatilimab were noted regardless of last prior therapy, and investigators reported a trend towards higher organ-specific response rates for those treated in their last LOT with rituximab compared with belumosudil. The sites or organs affected included the joints/fascia, mouth, lungs, eyes, and skin.

AGAVE-201 Study Design

In AGAVE-201, patients were randomly assigned 1:1:1 to receive either 0.3 mg/kg of axatilimab every 2 weeks (n = 80), 1.0 mg/kg of axatilimab every 2 weeks (n = 81), or 3.0 mg/kg of axatilimab every 4 weeks (n = 80).2

The primary end point was ORR, and the secondary end point was patient-reported decrease in cGVHD symptom burden.2 The most common adverse effects (AEs) were dose-dependent transient laboratory abnormalities related to CSF-1R blockade. Axatilimab was discontinued due to AEs in 6.0% of patients treated with the 0.3-mg dose, 22.0% in the 1-mg dose group, and 18.0% in the 3-mg disease group.2

In the post hoc analysis, ORR, TTR, SRR defined as proportion of patients with responses lasting over 20 weeks, and organ-specific responses were assessed by number of prior LOT and last therapy, such as ruxolitinib, belumosudil (Rezurock), and other therapies.

The median age for patients who received the 0.3 mg/kg dose was 50.0 years (range, 7-76); for all doses, the median age was 53.0 years (range, 7-81). The majority of patients were male, 58.8% and 62.7%, respectively, and the number of organs involved at baseline were the same, 8% for both.

Overall, the findings demonstrate the efficacy of axatilimab for steroid-refractory cGVHD after 2 LOT, including patients treated with rituximab as last LOT. The investigators cautioned that the small patient numbers and mixed treatment regimens may limit the interpretation of the data.

In August 2024, the FDA approved axatilimab for the treatment of adult and pediatric patients weighing at least 40 kg patients with cGVHD following disease progression on at least 2 prior lines of therapy.3 The approval was supported by findings from AGAVE-201.

References

1. Kitko CL, Mehta RS, Popradi G, et al. The effects of prior lines of therapy on clinical outcomes for patients with chronic graft-versus-host disease receiving axatilimab: a post hoc analysis of Agave-201. Presented at: 2025 Transplantation & Cellular Therapy Meetings; February 12-15, 2025; Honolulu, HI, Abstract 387.
2. Wolff D, Cutler C, Lee SJ, et al. Axatilimab in recurrent or refractory chronic graft-versus-host disease. N Engl J Med. 2024;391(11):1002-1014. doi:10.1056/NEJMoa2401537
3. FDA approves axatilimab-csfr for chronic graft-versus-host disease. FDA. August 14, 2024. Accessed February 14, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axatilimab-csfr-chronic-graft-versus-host-disease#:~:text=On%20August%2014%2C%202024%2C%20the,be%20posted%20on%20Drugs@FDA