Axatilimab for Refractory Chronic Graft-vs-Host Disease

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In a phase I/II study reported in the Journal of Clinical Oncology, Carrie L. Kitko, MD, and colleagues found that axatilimab, an anti–colony-stimulating factor 1 receptor (CSF-1R) antibody, produced high response rates in patients who had undergone allogeneic hematopoietic cell transplantation and had chronic graft-vs-host disease (GVHD) after failure of at least two prior systemic therapies.

As stated by the investigators, “Chronic GVHD remains the major cause of late morbidity after allogeneic hematopoietic cell transplantation. CSF-1R–dependent macrophages promote chronic GVHD fibrosis, and their elimination in preclinical studies ameliorated chronic GVHD. Axatilimab is a humanized monoclonal antibody that inhibits CSF-1R signaling and restrains macrophage development.”

Study Details

The U.S.-based multicenter trial enrolled 40 patients aged 6 years or older between February 2019 and April 2021, including 17 patients into phase I and 23 into phase II. In phase I dose escalation, patients received 0.15 mg/kg, 0.5 mg/kg, and 1 mg/kg of axatilimab once every 2 weeks and 3 mg/kg once every 2 or 4 weeks. The primary objective in phase II was to determine the overall response rate (complete and partial responses) at the start of treatment cycle 7.

Targeting profibrotic macrophages with axatilimab is a therapeutically promising novel strategy with a favorable safety profile for refractory chronic GVHD.
— Carrie L. Kitko, MD, and colleagues

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Key Findings

In phase I, two dose-limiting toxicities were reported, both at 3 mg/kg once every 2 weeks: grade 4 creatine phosphokinase (CPK) elevation with evidence of inflammatory myopathy in a patient with preexisting myositis and grade 2 CPK elevation at baseline, and grade 3 lipase elevation without evidence of pancreatitis.

All 23 patients in phase II received 1 mg/kg of axatilimab once every 2 weeks.

Among 22 evaluable patients in phase II, the overall response rate at cycle 7 day 1 was 50.0% (11 of 22; 90% confidence interval [CI] = 31%–69%). The overall response rate during the first six cycles was 82% (18 of 22; 95% CI = 60%–95%) in the phase II cohort and 67% (26 of 39; 95% CI = 50%–81%) in the entire study population. Responses were observed in all affected organs, regardless of prior therapy.

Among all 40 patients, treatment-related grade ≥ 3 adverse events occurred in 8 (20%), most commonly hypertension in 4 (10%), CPK increase in 4 (10%), and pneumonia in 3 (7.5%). Most were considered on-target effects of CSF-1R blockade, including CPK increase in four patients; increased aspartate aminotransferase, increased gamma-glutamyl transferase, and increased lipase in two patients each; and increased alanine aminotransferase and periorbital edema in one patient each. Treatment was discontinued due to treatment-related adverse events in four patients. No cytomegalovirus reactivations were observed.

A clinically meaningful improvement in chronic GVHD–related symptoms—as indicated by an increase in the summary Lee Symptom Scale of ≥ 7 points—was observed in 21 (58%) of 36 evaluable patients.

On-target activity of axatilimab was suggested by a decrease in skin CSF-1R–expressing macrophages.

The investigators concluded, “Targeting profibrotic macrophages with axatilimab is a therapeutically promising novel strategy with a favorable safety profile for refractory chronic GVHD.”

Dr. Kitko, of Vanderbilt University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Syndax Pharmaceuticals, Inc. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.