Phase 2 study of natalizumab plus standard corticosteroid treatment for high-risk acute graft-versus-host disease

Al Malki MM, London K, Baez J, Akahoshi Y, Hogan WJ, Etra A, Choe H, Hexner E, Langston A, Abhyankar S, Ponce DM, DeFilipp Z, Kitko CL, Adekola K, Reshef R, Ayuk F, Capellini A, Chanswangphuwana C, Eder M, Eng G, Gandhi I, Grupp S, Gleich S, Holler E, Javorniczky NR, Kasikis S, Kowalyk S, Morales G, Özbek U, Rösler W, Spyrou N, Yanik G, Young R, Chen YB, Nakamura R, Ferrara JL, Levine JE (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 7

Pages Range: 5189-5198

Journal Issue: 17

DOI: 10.1182/bloodadvances.2023009853

Abstract

Graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract is the main cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation. Ann Arbor (AA) scores derived from serum biomarkers at onset of GVHD quantify GI crypt damage; AA2/3 scores correlate with resistance to treatment and higher NRM. We conducted a multicenter, phase 2 study using natalizumab, a humanized monoclonal antibody that blocks T-cell trafficking to the GI tract through the α4 subunit of α4β7 integrin, combined with corticosteroids as primary treatment for patients with new onset AA2/3 GVHD. Seventy-five patients who were evaluable were enrolled and treated; 81% received natalizumab within 2 days of starting corticosteroids. Therapy was well tolerated with no treatment emergent adverse events in <10% of patients. Outcomes for patients treated with natalizumab plus corticosteroids were compared with 150 well-matched controls from the MAGIC database whose primary treatment was corticosteroids alone. There were no significant differences in overall or complete response between patients treated with natalizumab plus corticosteroids and those treated with corticosteroids alone (60% vs 58%; P = .67% and 48% vs 48%; P = 1.0, respectively) including relevant subgroups. There were also no significant differences in NRM or overall survival at 12 months in patients treated with natalizumab plus corticosteroids compared with controls treated with corticosteroids.

Authors with CRIS profile

Involved external institutions

City of Hope Medical Center United States (USA) (US) Icahn School of Medicine at Mount Sinai United States (USA) (US) Mayo Clinic United States (USA) (US) Ohio State University United States (USA) (US) Penn Medicine United States (USA) (US) Emory University United States (USA) (US) University of Kansas Medical Center United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Massachusetts General Hospital United States (USA) (US) Vanderbilt University United States (USA) (US) Northwestern University United States (USA) (US) Columbia University Irving Medical Center (CUIMC) United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) King Chulalongkorn Memorial Hospital / โรงพยาบาลจุฬาลงกรณ์ Thailand (TH) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Children's Hospital of Philadelphia United States (USA) (US) Universität Regensburg Germany (DE) Universitätsklinikum Freiburg Germany (DE) University of Michigan United States (USA) (US)

How to cite

APA:

Al Malki, M.M., London, K., Baez, J., Akahoshi, Y., Hogan, W.J., Etra, A.,... Levine, J.E. (2023). Phase 2 study of natalizumab plus standard corticosteroid treatment for high-risk acute graft-versus-host disease. Blood Advances, 7(17), 5189-5198. https://doi.org/10.1182/bloodadvances.2023009853

MLA:

Al Malki, Monzr M., et al. "Phase 2 study of natalizumab plus standard corticosteroid treatment for high-risk acute graft-versus-host disease." Blood Advances 7.17 (2023): 5189-5198.

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