AGAVE-201 Secondary Analysis Supports Bone Health Safety of Axatilimab in Chronic GVHD: Amandeep Salhotra, MD

Although chronic graft-vs-host disease (GVHD) is already associated with bone loss, investigators sought to determine whether axatilimab (Niktimvo; Incyte/Syndax), a CSF1R-blocking monoclonal antibody, might further affect bone health due to that pathway's known role in bone remodeling.

In a recent interview, Amandeep Salhotra, MD, of City of Hope, discussed findings from a secondary analysis of the phase 2 AGAVE-201 trial (NCT04710576), which found no meaningful changes in bone turnover biomarkers or clinically significant increases in fractures or other bone-related adverse events among patients receiving axatilimab for chronic GVHD. He also explained why longer-term follow-up, including longitudinal bone density assessments, will be necessary to better understand the therapy's effects on bone metabolism.

Salhotra was the lead author of the analysis, titled “Assessments of Bone Health Among Patients With Chronic Graft-versus-Host Disease Receiving Axatilimab in the AGAVE-201 Trial,” which he presented at the European Hematology Association 2026 Congress in Stockholm, Sweden.

This transcript has been lightly edited for clarity.

AJMC: Bone mineral density (BMD) loss is already a well-recognized complication of chronic GVHD. Why did bone health become a question of interest, specifically for axatilimab?

Salhotra: In some animal studies, it has been known that the CSF1R pathway is involved in bone remodeling, and axatilimab is a monoclonal antibody that blocks this pathway activated in monocytes and macrophages. So, there was a concern, or at least a safety issue, of whether the BMD would be affected or whether there would be any effect on the bone health of patients who are on these medications. Typically, patients with chronic GVHD have osteopenia and osteoporosis due to prior steroid use and lack of gonadal hormones. There's a possibility that this might be worsened, so the BMD markers were studied carefully in this study in patients who were on study.

AJMC: Building on that, what were the objectives and methods of this bone health analysis?

Salhotra: Essentially, AGAVE-201, just to back up a little bit, was a phase 2 study of axatilimab, which is the CSF1R receptor–blocking monoclonal antibody. There were 3 doses at which patients were treated: 0.3 mg/kg every 2 weeks, then there were higher doses of 1 mg/kg every 2 weeks, and then the highest dose level was 3 mg/kg every 4 weeks.

Across these 3 dose levels, approximately 80 patients were treated in each arm, so 240 patients in aggregate. The primary outcome was to look at the GVHD response kinetics and objectives; cycle 7, day 1, was essentially when we did the assessments. We're familiar with the fact that the [dose of] 0.3 mg/kg every 2 weeks was finally FDA approved based on its safety signal and efficacy signal in chronic GVHD.

One of the secondary objectives, which we're going to discuss today, was to see how these patients did in terms of their bone density markers. Coming into the study, at least at the FDA-approved dose levels, either osteopenia or osteoporosis was present in approximately 40% of these patients. The majority of the patients on study were on concomitant steroids, which have an effect on BMD.

There were 2 blood-based biomarkers that were used to look at the bone turnover. One was bone alkaline phosphatase, and then there were C-telopeptide blood levels; these were done at baseline and 6 months into the study. Patients who came off the study then had another blood draw done at the end of treatment.

We also looked at the adverse effects associated with bone health, so treatment-emergent adverse events associated specifically with bone health. We also looked at other clinical outcomes like the incidence of fractures in patients who were on study. Those are the biomarkers and the clinical end points that we use to assess bone health in patients on study.

AJMC: What were the main findings? Did any surprise you?

Salhotra: Looking at the bone turnover markers, specifically the alkaline phosphatase and C-telopeptide class 1 collagen levels, there was no significant change in patients who were on study. We looked at levels, again, as said, at baseline and 6 months at the end of study. These turnover markers were not significantly different in patients who were on study.

Then, looking at some of the treatment-emergent adverse events, the incidence of osteopenia was approximately 4% in patients, at least in the FDA-approved dose levels. Few patients had osteoarthritis, I think less than 5% or so, so at least from a clinical end point, there was no significant increase in the treatment-emergent adverse events, specifically pertaining to bone health.

Fractures were seen in approximately 7% of patients across the study, and approximately 7 patients, or less than 5%, had 2 or more fractures in any given site. Again, patients who are post transplant with chronic GVHD are at increased risk of fractures, but it seems like this was not over and above or significantly elevated in patients who were on axatilimab.

So, what we concluded from this secondary outcome is that the blood-based biomarkers were not significantly different in patients who were on axatilimab, and there were no unusual clinical adverse effects of axatilimab in patients who were on treatment, looking at incidents of osteopenia, osteoporosis, or incidence of fractures.

I will emphasize that, again, the majority of the patients, 65% of the patients on the study, were on concomitant corticosteroids. They probably came in with some amount of osteopenia or osteoporosis, but despite this higher spatial population, the skeletal events were not significantly elevated.

AJMC: Looking ahead, what additional research or follow-up analyses are needed to better understand the relationship between axatilimab and bone metabolism?

Salhotra: I think long-term follow-up is needed, given the findings from animal studies, where bone remodeling can be affected. So, studies like a DXA scan, which look at the density of the bones, can probably be done in a longitudinal fashion.

Longer-term follow-up is also needed; sometimes delayed effects can be seen. 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. 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.