Abstract Introduction: Chronic graft-versus-host disease (cGVHD) is an immune-mediated complication of allogeneic hematopoietic stem cell transplantation that leads to significant morbidity and mortality. Axatilimab (AXA) is a high-affinity monoclonal antibody that targets colony-stimulating factor 1 receptor (CSF-1R) signaling to deplete CSF-1R–dependent monocytes and macrophages, which are key drivers of inflammation and fibrosis in patients with cGVHD. Based on results from the pivotal phase 2 AGAVE-201 study (NCT04710576), the US Food and Drug Administration approved AXA 0.3 mg/kg every 2 weeks (Q2W) for patients with cGVHD after failure of ≥2 prior lines of systemic therapy. AXA was previously available for eligible patients with cGVHD in the US through an expanded access program (EAP) sponsored by Incyte Corporation (NCT05544032). Aims: To report a safety analysis of AXA among patients enrolled in the Incyte-sponsored US EAP. Methods: Patients aged ≥6 years with active, refractory or recurrent cGVHD and ≥2 prior lines of therapy (LOT) who were not participating in an AXA clinical trial were eligible to enroll in this open-label, multicenter EAP. Patients' relevant disease history prior to AXA initiation was recorded. Concurrent use of other cGVHD treatments was permitted at clinician discretion. Enrolled patients were treated with AXA 0.3 mg/kg Q2W; patients received treatment at clinician discretion for as long as clinical benefit was observed and/or treatment withdrawal criteria were not met, or closure of the EAP due to commercial availability. Treatment-emergent adverse events (TEAEs) were assessed from the time of consent until 30 days after the end of treatment or transition to commercial product among patients who received AXA in the EAP. All data were summarized using descriptive statistics. Results: The EAP enrolled 112 patients, 104 of whom received AXA. Among patients who received AXA, median (range) baseline age and weight were 51.0 (6–82) years and 73.3 (13.8–133.0) kg, respectively; 54.8% were male. At the time of AXA initiation, the organs involved included the skin (72.1%), eyes (62.5%), lungs (49.0%), mouth (47.1%), joints (40.4%), gastrointestinal tract (31.7%), liver (22.1%), and genital tract (6.7%). Many patients (44.2%) received ≥5 prior LOT, while 43.3%, 10.6%, and 1.0% received 3–4, 2, and 1 prior LOT, respectively. The most common prior systemic cGVHD treatments were belumosudil (80.8%), ruxolitinib (76.0%), and prednisone (74.0%). The most common concomitant cGVHD medications were belumosudil (65.4%), prednisone (60.6%), and ruxolitinib (51.0%). The median (range) duration of AXA treatment through the EAP was 143.0 (19–337) days. As of the data cutoff of June 13, 2025, 72/112 patients (64.3%) continued to receive AXA either through the EAP (n=2) or had transitioned to commercial product (n=70). Reasons for treatment discontinuation included death (n=11 9.8%), withdrawal of consent (n=6 5.4%), unacceptable toxicity (n=3 2.7%), cGVHD progression (n=2 1.8%), malignancy relapse (n=2 1.8%), inability to tolerate AXA (n=2 1.8%), and further participation would be injurious to the patient's health or well-being (n=1 0.9%). Forty-three patients (41.3%) reported serious TEAEs, most commonly hypoxia (n=5 4.8%), respiratory failure, (n=5 4.8%), pneumonia (n=4 3.8%), abdominal pain (n=3 2.9%), upper respiratory infection (n=3 2.9%), fever (n=2 1.9%), generalized muscle weakness (n=2 1.9%), and sepsis (n=2 1.9%). Seventy-five patients (72.1%) experienced TEAEs (any severity), most commonly (≥7%) increased aspartate aminotransferase (n=9 8.7%), nausea (n=9 8.7%), abdominal pain (n=8 7.7%), cough (n=8 7.7%), fatigue (n=8 7.7%), hypokalemia (n=8 7.7%), and hyponatremia (n=8 7.7%). Conclusion: This EAP represents the largest collated experience of AXA treatment in cGVHD outside of the AGAVE-201 trial. The safety profile of AXA was consistent with that observed in clinical trials, and no new or unexpected toxicities were reported. Patients received prior cGVHD treatments and had multi-organ involvement. Only 5 patients (4.5%) discontinued treatment due to unacceptable toxicity or inability to tolerate AXA, and the majority (62.5%) successfully transitioned to commercial product, suggesting ongoing clinical benefit. This analysis provides additional evidence of the safety and tolerability of AXA in the treatment of cGVHD.
Stein et al. (Mon,) studied this question.