Increased Dose of Axatilimab Noted as Tolerable in cGVHD

“Overall, these findings support the safety and feasibility of axatilimab at a dose of 0.6 mg/kg monthly,” said Nosha Farhadfar, MD.

Increasing axatilimab (Niktimvo) from 0.3 mg/kg every 2 weeks to 0.6 mg/kg every 4 weeks was tolerable for the treatment of chronic graft-vs-host disease (cGVHD), according to results from the phase 2 AGAVE-201 trial (NCT04710576) presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.

“Overall, these findings support the safety and feasibility of axatilimab at a dose of 0.6 mg/kg monthly,” Nosha Farhadfar, MD, of Methodist Physicians Texas Transplant Specialists - Adult Blood Marrow Transplant, San Antonio, Texas, said during a presentation of the data. “Future analyses are planned to further evaluate the efficacy and safety at this dosing. Also, I think we need real-world evidence, which is essential to complement this finding and provide a broader support for the therapeutic approach.”

AGAVE-201 Trial Design

In the AGAVE-201 trial, patients who met pre-specified criteria could change their dosing schedule from 0.3 mg/kg every 2 weeks to 0.6 mg/kg every 4 weeks, without dose capping. Investigators evaluated the safety and feasibility of transitioning from the approved dose using long-term data from the trial.

Among the 19 patients who transitioned to the 0.6-mg/kg dose, median age was 50 years (range, 20–73), with the majority being male (63.2%). Median time from diagnosis to randomization was 4.39 months (range, 1.4–17.6), and the median number of organs involved was 3. The majority of patients reported with severe disease (73.7%), and had previously received an FDA-approved agent (89.5%).

“The subgroup that transitioned to monthly dosing was generally comparable to the overall [population who received the 0.3 mg/kg dose every 2 weeks,]” Farhadfar said.

Treatment with a dose of 0.6 mg/kg every 4 weeks led to an overall response rate of 94.7% (95% CI, 74.0%–99.9%), including partial and complete response rates of 89.5% and 5.3%, respectively.

“One patient with stable disease was transitioned to multi-dosing at the investigator’s discretion,” Farhadfar added.

Toxicities After Switching Doses

After switching doses, patients were on treatment for a median of 20.9 months (range, 2–32). At data cutoff, 16 patients (84.2%) maintained the 0.6 mg/kg dose. Of the 3 who did not, 2 patients switched back to the FDA-approved dose at 4.6 and 18.6 months following the switch, respectively, while 1 patient switched back due to an adverse event (AE) at 3.4 months. In the overall population, the treatment duration was 7.4 months. (range, 6–14).

Farhadfar noted that the incidence of grade 3 or higher AEs was higher with the monthly dose compared with the FDA-approved dose (52.6% vs 36.8%, respectively), which was to be expected given the longer treatment duration seen.

“However, when you look at the incidence of treatment-related adverse event, this is similar before and after the monthly dosing, suggesting that the increase in adverse event may be more reflective of longer treatment exposure rather than the direct effect of a new dosing schedule.”

After the switch, there was also a higher incidence of serious AEs (42.1% vs 5.3%, respectively); however, less patients had dose interruptions (21.1% vs 36.8%). Investigators saw a slight increase in the amount of dose reductions (3 vs 0, respectively) and discontinuations (3 vs 0).

The most common AEs included fatigue (26.3%), upper respiratory tract infection (26.3%), headache (21.1%), abdominal pain (15.8%), cough (15.8%), creatine phosphokinase increase (15.8%), diarrhea (15.8%), falls (15.8%), oropharyngeal pain (15.8%), pruritis (15.8%), and pyrexia (15.8%).

In August 2024, the FDA approved axatilimab 0.3 kg/mg every 2 weeks for the treatment of cGVHD in patients who previously received 2 or more lines of therapy, based on results from the AGAVE-201 trial.2 Farhadfar emphasized that the 0.6-mg/kg dose is an investigational schedule change.

“So we need to interpret the results [cautiously], as the available efficacy data for the monthly dosing are limited and the sample size is very small,” she added.1 “My personal preference is to keep the patient at the every-2-weeks dosing, and consider transitioning to monthly dosing only in a situation where the patients are unable, unwilling, or there are some challenges that make this every-2-weeks dosing impractical.”

References

1. Farhadfar N, Soto SS, Chhabra S, et al. Safety and feasibility of 0.6 mg/kg every 4 weeks dosing of axatilimab in patients treated in the AGAVE-201 study. Blood. 2025;146(Supplement 1): abstract 272. doi:10.1182/blood-2025-272.

2. FDA approves axatilimab-csfr for chronic graft-versus-host disease. News release. FDA. August 14, 2024. Accessed December 6, 2025. https://tinyurl.com/3sn66tn3