Axatilimab Has No Bone Safety Concerns in cGVHD: Amandeep Salhotra, MD

In an interview following the European Hematology Association 2026 Congress, Amandeep Salhotra, MD, of City of Hope, discussed a bone health analysis from AGAVE-201 (NCT04710576), a phase 2 study evaluating axatilimab (Niktimvo; Incyte/Syndax), a CSF1R receptor-blocking monoclonal antibody used to treat chronic graft-versus-host disease (GVHD). As the lead author, he presented the abstract, “Assessments of Bone Health Among Patients With Chronic Graft-versus-Host Disease Receiving Axatilimab in the AGAVE-201 Trial,” at the annual meeting last month in Stockholm, Sweden.

The treatment received FDA approval in August 2024 for adults and children with chronic GVHD weighing at least 88.2 lbs, with a recommended dosage of 0.3 mg/kg. Salhotra explained that bone health was the central focus of the analysis since CSF1R signaling is involved in bone remodeling in animal studies. This raised concern that blocking this pathway could worsen bone mineral density in a patient population already prone to osteopenia and osteoporosis from prior steroid use and gonadal hormone deficiency.

The study evaluated about 240 patients across 3 dose levels: 0.3 mg/kg every 2 weeks, 1 mg/kg every 2 weeks, and 3 mg/kg every 4 weeks. Most patients were on concomitant steroids, with about 40% of patients receiving the 0.3 mg/kg dose having osteopenia or osteoporosis at baseline. Bone health was assessed using bone alkaline phosphatase and C-telopeptide, 2 blood-based turnover markers measured at baseline, 6 months, and the end of treatment. Bone-related adverse events and fracture incidence were also tracked.

Salhotra reported no significant change in bone turnover markers over the study period. Treatment-emergent osteopenia occurred in about 4% of patients, osteoarthritis in under 5%, and fractures in approximately 7%, with fewer than 5% experiencing multiple fractures. Despite 65% of patients being on concomitant corticosteroids, skeletal events were not significantly elevated, suggesting axatilimab did not meaningfully worsen bone health in this population.

Looking forward, Salhotra emphasized the need for longer-term follow-up, including longitudinal DXA scans, to capture potential delayed effects of prolonged axatilimab exposure. He noted future research should also explore whether interventions like calcium and vitamin D supplementation or bisphosphonates could mitigate any bone-related risks that emerge over time in patients on extended treatment.

“We have study data and the blood-based biomarker data for the patients who are on study, but what happens a year or 2 years later in patients who had prolonged exposure to these drugs is important,” Salhotra concluded. “And if there are any adverse effects of treatment, especially on bone health, can that be mitigated by calcium and vitamin D supplementation and the addition of bisphosphonate-type treatment? Those would be further areas of study when patients are on axatilimab.”