The Effects of Prior Lines of Therapy on Clinical Outcomes for Patients with Chronic Graft-Versus-Host Disease Receiving Axatilimab: A Post Hoc Analysis of Agave-201

Axatilimab (AXA) is a novel colony-stimulating factor 1 receptor (CSF-1R)–blocking antibody that targets the monocytes and macrophages associated with chronic graft-versus-host disease (cGVHD) pathogenesis. In the AGAVE-201 pivotal trial (NCT04710576), AXA 0.3 mg/kg once every 2 wk (Q2W; FDA-approved dose), demonstrated high response rates and was generally well tolerated in patients with cGVHD. To evaluate the effects of prior lines of therapy (LOT) on clinical outcomes with AXA among patients with cGVHD in AGAVE-201. Patients were randomized 1:1:1 to intravenous AXA (0.3 mg/kg Q2W; 1 mg/kg Q2W; 3 mg/kg Q4W). Overall response rate (ORR), time to first response (TTR), sustained response rate (SRR; proportion of patients with responses lasting ≥20 wk based on a landmark analysis of duration of response), and organ-specific responses were assessed post hoc by number of prior LOT and last therapy (ruxolitinib [RUX], belumosudil [BEL], and other therapies [all therapies other than RUX, including BEL]). LOT were clinically adjudicated for this analysis. The demographics and baseline clinical characteristics of patients in AGAVE-201 are summarized in Table 1 . ORRs with AXA were similar for patients whose best response to last prior treatment was a complete or partial response (65%), no change (62%), and progression (63%; Table 2 ). ORRs were consistent, with slight increases among patients who received a greater number of prior LOT (2 LOT, 51%; 3 LOT, 61%; 4 LOT, 63%; ≥4 LOT, 67%). ORR in the 68 patients treated with RUX in last LOT was 62%, with a median (range) TTR of 1.9 (0.9–5.8) months and SRR of 43% (95% CI, 31%–55%). Among those treated with BEL in last LOT (n=34), ORR was 50%, median (range) TTR was 1.9 (0.9–3.9) months, and SRR was 26% (95% CI, 13%–44%); responses in patients with any therapy other than RUX in last LOT are shown in Table 2 . Organ-specific responses among patients with RUX, other therapies, or BEL in last LOT are summarized in the Figure . In AGAVE-201, ORRs and response durability with AXA were consistent regardless of the number of prior LOT received. Patients who received AXA immediately after a regimen with RUX demonstrated rapid, durable clinical responses. Organ-specific responses to AXA were noted regardless of last prior therapy, and there is a trend towards higher organ-specific response rates for those treated in their last LOT with RUX compared with BEL in some organs (joints/fascia, mouth, lungs, eyes, and skin). This finding warrants further investigation and may be attributable to the novel mechanism of action of AXA or LOT. Small patient numbers and mixed treatment regimens may limit interpretation. These data demonstrate the efficacy of AXA for steroid-refractory cGVHD after 2 LOT, including patients treated with RUX as last LOT.

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