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Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease.
Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease.
- Source :
-
The New England journal of medicine [N Engl J Med] 2024 Sep 19; Vol. 391 (11), pp. 1002-1014. - Publication Year :
- 2024
-
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.<br />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%.<br />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.<br />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.).<br /> (Copyright © 2024 Massachusetts Medical Society.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Child
Female
Humans
Male
Middle Aged
Young Adult
Chronic Disease drug therapy
Dose-Response Relationship, Drug
Infusions, Intravenous
Recurrence
Severity of Illness Index
Treatment Outcome
Antibodies, Monoclonal, Humanized administration & dosage
Antibodies, Monoclonal, Humanized adverse effects
Graft vs Host Disease diagnosis
Graft vs Host Disease drug therapy
Graft vs Host Disease immunology
Graft vs Host Disease metabolism
Hematopoietic Stem Cell Transplantation adverse effects
Receptor, Macrophage Colony-Stimulating Factor antagonists & inhibitors
Receptor, Macrophage Colony-Stimulating Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1533-4406
- Volume :
- 391
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The New England journal of medicine
- Publication Type :
- Academic Journal
- Accession number :
- 39292927
- Full Text :
- https://doi.org/10.1056/NEJMoa2401537