Axatilimab Shows Long-Term Safety and Clinical Benefit in Pretreated Chronic GVHD

Axatilimab (Niktimvo) continued to be tolerable and effective despite prolonged treatment exposure in patients with chronic graft-vs-host-disease (GVHD) from the phase 2 AGAVE-201 trial (NCT04710576), according to long-term follow-up data presented at the 2025 ASH Annual Meeting.¹

With a median treatment duration of 34.0 months across all dose levels, 33 (13.8%) of the 239 patients who initially received axatilimab in the trial remained on treatment at the time of this analysis. The overall safety profile of axatilimab in these patients was similar to that of all treated patients in the trial.

“No new safety signals were observed. Incidences of treatment-emergent adverse events [TEAEs] including laboratory enzyme elevations, were similar to [that of] the primary analysis,” said Carrie L. Kitko, MD, associate professor of pediatrics at Vanderbilt University Medical Center, in her presentation of the data.

The AGAVE-201 trial investigated axatilimab, a CSF1R-targeted intravenous treatment, at 3 dose levels in patients who continued to have cGVHD after prior treatment. Based on the primary analysis, the FDA approved axatilimab at a dose of 0.3 mg/kg every 2 weeks after failure of at least 2 prior lines of systemic therapy.² There was an overall response rate of 74% in the first 6 treatment cycles.

As of March 30, 2025, 205 patients had discontinued treatment, 33 remained on treatment, and 1 completed treatment.¹ The approved 0.3 mg/kg dose level was given in 79 patients, with 81 patients receiving 1 mg/kg every 2 weeks and 79 patients receiving and 3 mg/kg every 4 weeks.

Treatment was allowed to continue for up to 2 years if the patient derived clinical benefit per investigator and the patient reported clinically meaningful symptomatic improvement.

After the initial 6 cycles, based on independent data monitoring committee recommendations, the 3 mg/kg dose group was reduced to 0.6 mg/kg and patients receiving 1 mg/kg could choose to continue this dose or reduce to 0.3 mg/kg. Patients who received either dose every 2 weeks could choose to receive 0.6 mg/kg every 4 weeks if they had a sustained response at 20 weeks.

Of 15 patients who initially received the 0.3 mg/kg dose every 2 weeks, 11 now received 0.6 mg/kg every 4 weeks, with others also receiving reduced or less frequent doses.

Long-term data were collected for OS, safety, and duration of treatment. Patients were followed for safety for 90 days after their last dose and overall survival (OS) data were collected for 5 years after safety follow-up.

What long-term safety outcomes were reported?

There were no new safety signals observed during long-term follow-up, and the incidence of TEAEs generally decreased after day 1 of cycle 7.

Fatigue, which was reported in 23.0% in the primary analysis, occurred at a 26.8% rate in the long term. COVID-19 occurred in 22.2% compared with 17.6%, and diarrhea occurred in 20.9% compared with 15.9% in the primary analysis. The incidence of periorbital edema was 18.4% in both analyses.

Rates of laboratory findings including elevated aspartate aminotransferase, alanine aminotransferase, and creatine phosphokinase were similar, and dose interruption and reduction rates caused by these changes were also similar in the primary and long-term analyses. No patient in the 0.3 mg/kg cohort discontinued treatment because of laboratory enzyme elevations.

Looking at the baseline characteristics of those who remained on treatment, they were similar to those of the overall enrolled population, with 75.8% having received prior ruxolitinib, 36.4% having received ibrutinib (Imbruvica), and 18.2% having received belumosudil (Rezurock). Patients had a median of 4 organs involved at baseline.

Serious TEAEs were reported in 48.5% across all doses and 53.3% in the 0.3 mg/kg group. The serious TEAEs observed in at least 1 patient consisted of pneumonia in 4 patients, COVID-19 in 2, and respiratory tract infection in 2.

Dose interruptions were needed because of TEAEs in 57.6% in all patients remaining on treatment and 60.0% in the 0.3 mg/kg group compared with 21.3% and 27.8%, respectively, among all treated patients, which investigators said could be attributed to the longer duration of treatment. The most common TEAEs that led to dose interruption were pneumonia and respiratory tract infection in 4 patients each, and COVID-19 and pyrexia in 3 patients each.

What did additional data from the survival analysis reveal about axatilimab's long-term benefit?

The long-term results also included a Kaplan-Meier estimate of OS in the intent-to-treat population. Median OS was not reached in any of the 3 treatment cohorts. In the 0.3 mg/kg cohort, the 46-month OS rate was 77.6% (95% CI, 57.8%-89.0%) with median follow-up of 31.7 months (range, 0-46.5), and across all doses it was 74.1% (64.8%-81.3%) with median follow-up of 31.2 months (range, 0-46.5). There were 10 OS events in the 0.3 mg/kg cohort, 20 in the 1 mg/kg cohort, and 16 in the 3 mg/kg cohort.

“In conclusion, during long-term safety follow-up of patients with cGVHD in the AGAVE-201 study, axatilimab had a continued tolerable safety profile and TEAEs generally decreased with prolonged exposure,” said Kitko. “Therapy with axatilimab can be considered to optimize clinical outcomes for patients with longstanding cGVHD.”

References

1. Kitko C, Salhotra A, Kwon M, et al. Long-term treatment duration and safety of axatilimab among patients with chronic graft-versus-host disease in AGAVE-201. Blood. 2025;146(suppl 1):6010. doi:10.1182/blood-2025-6010
2. FDA approves axatilimab-csfr for chronic graft-versus-host disease. FDA. August 14, 2024. Accessed December 9, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axatilimab-csfr-chronic-graft-versus-host-disease