Axatilimab Dose Transition Appears Feasible, Tolerable in cGVHD

Transitioning the dose of axatilimab (Niktimvo) from 0.3 mg/kg every 2 weeks to 0.6 mg/kg every 4 weeks appeared feasible in patients with chronic graft-versus-host disease (cGVHD), according to data from the pivotal phase 2 AGAVE-201 trial (NCT04710576).

“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, in San Antonio, 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 prespecified 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 multidosing 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 [AE], this is similar before and after the monthly dosing, suggesting that the increase in [AE] may be more reflective of longer treatment exposure rather than the direct effect of a new dosing schedule,” said Farhadfar.

After the switch, there was also a higher incidence of serious AEs (42.1% vs 5.3%, respectively); however, fewer 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. 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. “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.”

Reference

Farhadfar N, Soto MS, 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(suppl 1):272. doi:10.1182/blood-2025-272