Axatilimab Monthly Dosing Shows Promise for Chronic GVHD Treatment Convenience
核心洞察
A phase 2 AGAVE-201 trial demonstrated that transitioning axatilimab from 0.3 mg/kg every 2 weeks to 0.6 mg/kg every 4 weeks was feasible and tolerable for chronic graft-vs-host disease (搜索) patients.
Among 19 patients who switched to monthly dosing, the overall response rate reached 94.7% with 84.2% maintaining the higher dose regimen.
While grade 3+ adverse events increased with monthly dosing (52.6% vs 36.8%), researchers attributed this to longer treatment exposure rather than the dosing schedule itself.
Transitioning axatilimab (Niktimvo) to a monthly dosing schedule of 0.6 mg/kg every 4 weeks demonstrated safety and feasibility for patients with chronic graft-vs-host disease (搜索) (cGVHD (搜索)), according to new data from the phase 2 AGAVE-201 trial presented at the 2025 American Society of Hematology (搜索) Annual Meeting.
The findings suggest that patients currently receiving the FDA-approved dose of 0.3 mg/kg every 2 weeks could potentially transition to a more convenient monthly schedule without compromising safety, though researchers emphasized the need for cautious interpretation given the small sample size.
Trial Design and Patient Population
The AGAVE-201 trial allowed patients meeting pre-specified criteria to transition from the standard 0.3 mg/kg biweekly dose to 0.6 mg/kg every 4 weeks without dose capping. Among 19 patients who made this transition, the median age was 50 years (range, 20-73), with 63.2% being male.
The patient population reflected typical cGVHD (搜索) characteristics, with a median time from diagnosis to randomization of 4.39 months (range, 1.4-17.6) and a median of 3 organs involved. Notably, 73.7% presented with severe disease, and 89.5% had previously received an FDA-approved agent.
"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," said Nosha Farhadfar, MD, of Methodist Physicians Texas Transplant Specialists (搜索), who presented the data.
Efficacy and Treatment Duration
Treatment with the monthly 0.6 mg/kg dose achieved an overall response rate of 94.7% (95% CI, 74.0%-99.9%), including partial response rates of 89.5% and complete response rates of 5.3%. One patient with stable disease was transitioned to the monthly dosing at the investigator's discretion.
After switching to monthly dosing, patients remained on treatment for a median of 20.9 months (range, 2-32), compared to 7.4 months (range, 6-14) in the overall population. At data cutoff, 84.2% of patients (16 of 19) maintained the 0.6 mg/kg dose.
Of the three patients who discontinued monthly dosing, two switched back to the FDA-approved dose at 4.6 and 18.6 months respectively, while one patient switched back due to an adverse event at 3.4 months.
Safety Profile and Adverse Events
The monthly dosing schedule showed a manageable safety profile, though with some expected increases in adverse events due to longer treatment exposure. Grade 3 or higher adverse events occurred in 52.6% of patients on monthly dosing compared to 36.8% on the standard biweekly schedule.
"However, when you look at the incidence of treatment-related adverse events, this is similar before and after the monthly dosing, suggesting that the increase in adverse events may be more reflective of longer treatment exposure rather than the direct effect of a new dosing schedule," Farhadfar explained.
Serious adverse events increased to 42.1% from 5.3%, but dose interruptions actually decreased (21.1% vs 36.8%). The study observed slight increases in dose reductions (3 vs 0) and discontinuations (3 vs 0).
The most frequently reported adverse events included fatigue (26.3%), upper respiratory tract infection (26.3%), headache (21.1%), and several other events occurring in 15.8% of patients each: abdominal pain, cough, creatine phosphokinase increase, diarrhea, falls, oropharyngeal pain, pruritis, and pyrexia.
Clinical Implications and Future Directions
The FDA approved axatilimab at 0.3 mg/kg every 2 weeks in August 2024 for treating cGVHD (搜索) in patients who have received two or more prior lines of therapy, based on results from the AGAVE-201 trial. The 0.6 mg/kg monthly dose remains investigational.
"Overall, these findings support the safety and feasibility of axatilimab at a dose of 0.6 mg/kg monthly," Farhadfar stated. "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."
Farhadfar emphasized the need for careful patient selection for the monthly dosing schedule. "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."
The researchers cautioned that available efficacy data for monthly dosing remain limited due to the small sample size, underscoring the need for additional studies to establish the optimal dosing strategy for different patient populations.