Background
Phase 2, open-label, 3-arm dose-finding study (AGAVE-201). 241 patients with steroid-refractory/dependent chronic GVHD after allo-HCT who had received ≥2 prior lines. Axatilimab is a high-affinity monoclonal antibody targeting CSF1R (CD115), blocking macrophage/monocyte activation and differentiation — a key driver of fibrotic cGVHD. Mechanism is orthogonal to T-cell–directed approaches (calcineurin, JAK, ROCK2 inhibitors).
Interventions and follow up
Arm A: axatilimab 0.3mg/kg IV every 2 weeks (q2w)
Arm B: axatilimab 1.0mg/kg IV every 2 weeks (q2w)
Arm C: axatilimab 3.0mg/kg IV every 4 weeks (q4w)
Primary endpoint: Overall response rate per 2014 NIH cGVHD Consensus at cycle 7 day 1
Median follow up: 14.4 months
Arm B: axatilimab 1.0mg/kg IV every 2 weeks (q2w)
Arm C: axatilimab 3.0mg/kg IV every 4 weeks (q4w)
Primary endpoint: Overall response rate per 2014 NIH cGVHD Consensus at cycle 7 day 1
Median follow up: 14.4 months
Results
ORR (0.3mg/kg q2w): 74% (95% CI 62–84%)
ORR (1.0mg/kg q2w): 67% (95% CI 55–78%)
ORR (3.0mg/kg q4w): 50% (95% CI 38–62%)
CR/PR (0.3mg/kg): CR 7%, PR 67%
Median FFS (0.3mg/kg): not reached; 12-month FFS 52%
Fibrotic cGVHD activity: notable ORR in sclerotic/fibrotic skin and lung manifestations
ORR (1.0mg/kg q2w): 67% (95% CI 55–78%)
ORR (3.0mg/kg q4w): 50% (95% CI 38–62%)
CR/PR (0.3mg/kg): CR 7%, PR 67%
Median FFS (0.3mg/kg): not reached; 12-month FFS 52%
Fibrotic cGVHD activity: notable ORR in sclerotic/fibrotic skin and lung manifestations
Adverse events
Overall: grade ≥3 AEs 66% (0.3mg/kg) vs 77% (1mg/kg) vs 71% (3mg/kg)
CSF1R class effect: periorbital edema any grade 71% (0.3mg/kg), highest of all arms; manageable with dose interruption/reduction
Infections/organ: grade ≥3 infections 27%; CPK elevation 7%; grade ≥3 AST/ALT elevation 11%; grade ≥3 fatigue 8%
CSF1R class effect: periorbital edema any grade 71% (0.3mg/kg), highest of all arms; manageable with dose interruption/reduction
Infections/organ: grade ≥3 infections 27%; CPK elevation 7%; grade ≥3 AST/ALT elevation 11%; grade ≥3 fatigue 8%
Conclusions
Axatilimab 0.3mg/kg q2w demonstrated a 74% ORR in SR-cGVHD including fibrotic manifestations, supporting FDA approval as the first anti-CSF1R and first macrophage-directed agent for cGVHD treatment.
Key Limitations
Phase 2 dose-finding study without an active comparator arm. Periorbital edema is a nearly universal and potentially bothersome class effect of CSF1R inhibition (71% at the approved dose). IV q2w administration requires infusion-center access. Fibrotic cGVHD responses are encouraging but durability in this historically refractory manifestation requires longer follow-up. No head-to-head comparisons with belumosudil or ruxolitinib are available.
Clinical Context
FDA approved axatilimab-csfr (Niktimvo) in August 2024 for SR-cGVHD in adults and pediatric patients ≥2 years after ≥2 prior lines. Its macrophage/fibrosis-targeting mechanism is particularly promising for fibrotic cGVHD (sclerotic skin, bronchiolitis obliterans) where T-cell–directed therapies underperform. The SR-cGVHD landscape includes ibrutinib, ruxolitinib (REACH3, 2L standard), belumosudil (ROCK2, 3L+), and axatilimab (CSF1R, 3L+) per ASTCT practice.