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Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease.
N Engl J Med. 2024 Sep 19; 391(11):1002-1014.NEJM

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.).

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Authors+Show Affiliations

Wolff D
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Cutler C
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Lee SJ
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Pusic I
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Bittencourt H
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
White J
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Hamadani M
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Arai S
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Salhotra A
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Perez-Simon JA
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Alousi A
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Choe H
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Kwon M
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Bermúdez A
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Kim I
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Socié G
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Chhabra S
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Radojcic V
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
O'Toole T
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Tian C
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Ordentlich P
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
DeFilipp Z
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
Kitko CL
From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).
AGAVE-201 Investigators
No affiliation info available

MeSH

AdolescentAdultAgedAged, 80 and overChildFemaleHumansMaleMiddle AgedYoung AdultAntibodies, Monoclonal, HumanizedChronic DiseaseDose-Response Relationship, DrugGraft vs Host DiseaseHematopoietic Stem Cell TransplantationInfusions, IntravenousReceptor, Macrophage Colony-Stimulating FactorRecurrenceSeverity of Illness IndexTreatment Outcome

Pub Type(s)

Journal Article
Randomized Controlled Trial
Multicenter Study
Clinical Trial, Phase II

Language

eng

PubMed ID

39292927

Clinical Trial Links

Clinical trial which this article describes
Axatilimab Combined With Decitabine/Venetoclax for the Treatment of TP53-mutated AML

Citation

Wolff, Daniel, et al. "Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease." The New England Journal of Medicine, vol. 391, no. 11, 2024, pp. 1002-1014.
Wolff D, Cutler C, Lee SJ, et al. Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2024;391(11):1002-1014.
Wolff, D., Cutler, C., Lee, S. J., Pusic, I., Bittencourt, H., White, J., Hamadani, M., Arai, S., Salhotra, A., Perez-Simon, J. A., Alousi, A., Choe, H., Kwon, M., Bermúdez, A., Kim, I., Socié, G., Chhabra, S., Radojcic, V., O'Toole, T., ... Kitko, C. L. (2024). Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. The New England Journal of Medicine, 391(11), 1002-1014. https://doi.org/10.1056/NEJMoa2401537
Wolff D, et al. Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2024 09 19;391(11):1002-1014. PubMed PMID: 39292927.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. AU - Wolff,Daniel, AU - Cutler,Corey, AU - Lee,Stephanie J, AU - Pusic,Iskra, AU - Bittencourt,Henrique, AU - White,Jennifer, AU - Hamadani,Mehdi, AU - Arai,Sally, AU - Salhotra,Amandeep, AU - Perez-Simon,Jose A, AU - Alousi,Amin, AU - Choe,Hannah, AU - Kwon,Mi, AU - Bermúdez,Arancha, AU - Kim,Inho, AU - Socié,Gerard, AU - Chhabra,Saurabh, AU - Radojcic,Vedran, AU - O'Toole,Timothy, AU - Tian,Chuan, AU - Ordentlich,Peter, AU - DeFilipp,Zachariah, AU - Kitko,Carrie L, AU - ,, PY - 2024/9/18/medline PY - 2024/9/18/pubmed PY - 2024/9/18/entrez SP - 1002 EP - 1014 JF - The New England journal of medicine JO - N Engl J Med VL - 391 IS - 11 N2 - 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.). SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/39292927/Axatilimab_in_Recurrent_or_Refractory_Chronic_Graft-versus-Host_Disease DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓62]

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