Wolff, Daniel and Cutler, Corey and Lee, Stephanie J. and Pusic, Iskra and Bittencourt, Henrique and White, Jennifer and Hamadani, Mehdi and Arai, Sally and Salhotra, Amandeep and Perez-Simon, Jose A. and Alousi, Amin and Choe, Hannah and Kwon, Mi and Bermudez, Arancha and Kim, Inho and Socie, Gerard and Chhabra, Saurabh and Radojcic, Vedran and O'Toole, Timothy and Tian, Chuan and Ordentlich, Peter and Defilipp, Zachariah and Kitko, Carrie L. (2024) Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. NEW ENGLAND JOURNAL OF MEDICINE, 391 (11). pp. 1002-1014. ISSN 0028-4793, 1533-4406
Full text not available from this repository. (Request a copy)Abstract
Background Colony-stimulating factor 1 receptor (CSF1R)-dependent monocytes and macrophages are key mediators of chronic graft-versus-host disease (GVHD), a major long-term complication of allogeneic hematopoietic stem-cell transplantation. The CSF1R-blocking antibody axatilimab has shown promising clinical activity in chronic GVHD.Methods In this phase 2, multinational, pivotal, randomized study, we evaluated axatilimab at three different doses in patients with recurrent or refractory chronic GVHD. Patients were randomly assigned to receive axatilimab, administered intravenously, at a dose of 0.3 mg per kilogram of body weight every 2 weeks (0.3-mg dose group), at a dose of 1 mg per kilogram every 2 weeks (1-mg dose group), or at a dose of 3 mg per kilogram every 4 weeks (3-mg dose group). The primary end point was overall response (complete or partial response) in the first six cycles; the key secondary end point was a patient-reported decrease in chronic GVHD symptom burden, as assessed by a reduction of more than 5 points on the modified Lee Symptom Scale (range, 0 to 100, with higher scores indicating worse symptoms). The primary end point would be met if the lower bound of the 95% confidence interval exceeded 30%.Results A total of 241 patients were enrolled (80 patients in the 0.3-mg dose group, 81 in the 1-mg dose group, and 80 in the 3-mg dose group). The primary end point was met in all the groups; an overall response was observed in 74% (95% confidence interval [CI], 63 to 83) of the patients in the 0.3-mg dose group, 67% (95% CI, 55 to 77) of the patients in the 1-mg dose group, and 50% (95% CI, 39 to 61) of the patients in the 3-mg dose group. A reduction of more than 5 points on the modified Lee Symptom Scale was reported in 60%, 69%, and 41% of the patients in the three dose groups, respectively. The most common adverse events were dose-dependent transient laboratory abnormalities related to CSF1R blockade. Adverse events leading to discontinuation of axatilimab occurred in 6% of the patients in the 0.3-mg dose group, 22% in the 1-mg dose group, and 18% in the 3-mg dose group.Conclusions Targeting CSF1R-dependent monocytes and macrophages with axatilimab resulted in a high incidence of response among patients with recurrent or refractory chronic GVHD. (Funded by Syndax Pharmaceuticals and Incyte; AGAVE-201 ClinicalTrials.gov number, NCT04710576.) A study in patients with chronic GVHD evaluated three doses of axatilimab, a colony-stimulating factor 1 receptor antibody. The lowest dose appeared to maximize response with the fewest adverse effects.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CONSENSUS DEVELOPMENT PROJECT; CLINICAL-TRIALS; CSF-1 RECEPTOR; CRITERIA; MACROPHAGES; TRANSPLANTATION; GVHD; IV. |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Jan 2026 09:49 |
| Last Modified: | 27 Jan 2026 09:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65105 |
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