Hannah Choe, MD, on Dynamics of Overall and Organ-Specific Responses to Axatilimab in Chronic Graft-Versus-Host Disease: Analysis from the AGAVE-201 Study

Agave 2.01 was an open label multicenter, randomized study of axatilimab at three different doses. This study met its primary endpoint with an NIH clinical response rate of 73% within the first six treatment cycles. It also met its key secondary endpoint with a seven point or more improvement in the modified Lee symptom scale of 55.1% of patients. In this analysis that we presented in the abstract at ASH 2024, we looked at those responders with NIH clinical response or mLSS symptom response. We evaluate the dynamics of these responses overall and by organ and also between the NIH clinical and symptoms scores. Responsive patients reflected the overall study population. There was heavy pre-treatment and also majority of patients with severe disease. The fastest responding organs by clinical responses were the upper GI tract, lower GI tract, joints, fascia, esophagus, and liver. With median responses seen 1.0 to 1.9 months. More than half of these responses were seen by day 56, if not day 84. The more fibrotic manifestations, which included the mouth, lungs, eyes, and skin, took longer to respond with median 2.1 to 3.2 months. But interestingly, we found that patients had symptom improvements as seen by improvements in their mLSS symptom scales faster with their NIH clinical responses in these slower responsive organs, including the mouth, lungs, and eyes, and trended towards significance with the skin. These responses were seen in the first one to two months. We now understand better how and when patients respond to axatilimab as assessed by clinicians with the NIH clinical response and patients from the patient reported outcomes from the modified Lee symptom scale. Importantly, patients responded with symptom improvements preceding that of the clinician, and this was seen particularly with the fibrotic manifestations, axatilimab, thus demonstrated rapid activity, not just by clinical responses, but also even more so with symptom responses sooner. And overall, it was well tolerated as seen in the overall AGAVE 201 study.