Patients with chronic graft-versus-host disease (cGVHD) treated with axatilimab (Niktimvo) were able to remain on therapy without evidence of cumulative toxicity, according to long-term results presented at the 2025 ASH Annual Meeting.
Of 239 patients enrolled in the phase 2 AGAVE-201 trial (NCT04710576), 33 (13.8%) remained on axatilimab at a median of 34.0 months across all dose levels. As of March 30, 2025, 205 patients had discontinued treatment and one had completed the planned course. The safety profile among patients remaining on therapy was comparable to that seen in the overall trial population.
Axatilimab, a CSF1R-targeted intravenous therapy, was studied at three dose regimens. Based on the primary analysis, the FDA approved axatilimab at 0.3 mg/kg every two weeks for patients with cGVHD who have failed at least two prior lines of systemic therapy; the drug produced an overall response rate of 74% in the first six treatment cycles. In the trial, 79 patients received the approved 0.3 mg/kg dose, 81 received 1 mg/kg every two weeks, and 79 received 3 mg/kg every four weeks.
Dose modifications were implemented after an independent data monitoring committee review. The 3 mg/kg group was reduced to 0.6 mg/kg, patients receiving 1 mg/kg could continue or reduce to 0.3 mg/kg, and patients on every-two-week schedules could switch to 0.6 mg/kg every four weeks after a sustained response at 20 weeks. Of 15 patients initially treated at 0.3 mg/kg every two weeks, 11 later received 0.6 mg/kg every four weeks.
Long-term safety follow-up showed no new safety signals and a general decrease in treatment-emergent adverse events (TEAEs) after the start of cycle 7. Compared with the primary analysis, rates changed modestly: fatigue 26.8% versus 23.0%; COVID-19 22.2% versus 17.6%; diarrhea 20.9% versus 15.9%; periorbital edema 18.4% in both analyses. Laboratory elevations in AST, ALT, and CPK were similar to earlier reports, and no patient in the 0.3 mg/kg cohort discontinued due to enzyme elevations.
Baseline characteristics of patients who remained on treatment were similar to the overall cohort: 75.8% had received prior ruxolitinib, 36.4% had received ibrutinib, and 18.2% had received belumosudil. Patients had a median of four organs involved at baseline. Serious TEAEs were reported in 48.5% of patients remaining on treatment and 53.3% of the 0.3 mg/kg cohort; events reported in at least one patient included pneumonia (4 patients), COVID-19 (2), and respiratory tract infection (2).
Dose interruptions due to TEAEs were more common among patients remaining on long-term therapy (57.6% overall; 60.0% in the 0.3 mg/kg group) than in the full trial population (21.3% overall; 27.8% in the 0.3 mg/kg group), a difference investigators attributed to longer treatment duration. Pneumonia and respiratory tract infections were the most frequent causes of interruption (4 patients each), followed by COVID-19 and pyrexia (3 patients each).
Survival analysis showed median overall survival was not reached in any cohort. In the 0.3 mg/kg group, the 46-month overall survival rate was 77.6% (95% CI, 57.8%–89.0%) with a median follow-up of 31.7 months. Across all doses the 46-month overall survival rate was 74.1% (95% CI, 64.8%–81.3%) with a median follow-up of 31.2 months. There were 10 overall survival events in the 0.3 mg/kg cohort, 20 in the 1 mg/kg cohort, and 16 in the 3 mg/kg cohort.
“No new safety signals were observed. Incidences of treatment-emergent adverse events including laboratory enzyme elevations were similar to the primary analysis,” said Carrie L. Kitko, MD, in presenting the data, adding that axatilimab demonstrated a continued tolerable safety profile with TEAEs generally decreasing over time and can be considered to optimize outcomes for patients with longstanding cGVHD.
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