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Combination ruxolitinib, belumosudil, and axatilimab yields clinically significant symptomatic improvements in treatment-refractory chronic GVHD

Bone Marrow Transplantation volume 61, pages 121–123 (2026) Cite this article

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Chronic graft versus host disease (GVHD) is a significant complication of allogeneic hematopoietic cell transplants (HCT), affecting up to half of transplant recipients [1]. In recent years, several medications have received FDA approval for the treatment of refractory GVHD, including ibrutinib, ruxolitinib, belumosudil, and axatilimab. Despite this, complete and durable responses are uncommon [2]. In cases of incomplete response, the use of combination therapies has become more prevalent [3,4,5,6]. However, there is limited data on the outcomes associated with different combinations, as the use of these medications in combination has yet to be studied on a clinical trial.

In contrast to ruxolitinib and belumosudil, which function via inhibition of the JAK and ROCK2 pathways respectively [7, 8], axatilimab is a monoclonal antibody that targets Colony-Stimulating Factor 1 Receptor (CSF-1R) signaling in macrophages [9, 10]. Axatilimab was recently studied in a Phase II trial (AGAVE-201) leading to FDA approval [9, 10]. The use of ruxolitinib and belumosudil were prohibited on the AGAVE-201 trial, but their use in combination in the commercial setting is a likely treatment approach. Herein, we present a retrospective analysis of chronic GVHD patients treated with axatilimab in combination ruxolitinib and/or belumosudil.

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References

  1. Langer R, Lelas A, Rittenschober M, Piekarska A, Sadowska-Klasa A, Sabol I, et al. Retrospective analysis of the incidence and outcome of late acute and chronic graft-versus-host disease-an analysis from transplant centers across Europe. Front Transpl. 2024;3:1332181. https://doi.org/10.3389/frtra.2024.1332181.

    Article  Google Scholar 

  2. Martini D, Chen Y, DeFilipp Z. Recent FDA Approvals in the Treatment of Graft-Versus-Host Disease. Oncologist. 2022;27:685–93. https://doi.org/10.1093/oncolo/oyac076.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gagliardi T, Milner J, Cairo M, Steinberg A. Concomitant Ruxolitinib and Ibrutinib for Graft-Versus-Host Disease (GVHD): The First Reported Use in Pediatric Patients. Cureus. 2022;14:e29195. https://doi.org/10.7759/cureus.29195.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Belizaire R, Kim H, Poryanda S, Mirkovic N, Hipolito E, Savage W, et al. Efficacy and immunologic effects of extracorporeal photopheresis plus interleukin-2 in chronic graft-versus-host disease. Blood Adv. 2019;3:969–79. https://doi.org/10.1182/bloodadvances.2018029124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chin M, Shizuru J, Muffly L, Shiraz P, Johnston L, Lowsky R. Belumosudil Combination Therapy in Refractory Chronic Graft-Versus-Host Disease. Blood. 2022;140:4788–9. https://doi.org/10.1182/blood-2022-165547.

    Article  Google Scholar 

  6. Lee S, Nguyen T, Onstad L, Bar M, Krahow E, Salit R, et al. Success of Immunosuppressive Treatments in Patients with Chronic Graft-versus-Host Disease. Biol Blood Marrow Transpl. 2018;24:555–62.

    Article  CAS  Google Scholar 

  7. Zeiser R, Polverelli N, Ram R, Hashmi S, Chakraverty R, Middeke J, et al. Ruxolitinib for Glucocorticoid-Refractory chronic graft-versus-host disease. N Engl J Med. 2021;385:228–38.

    Article  CAS  PubMed  Google Scholar 

  8. Cutler C, Lee S, Arai S, Rotta M, Zoghi B, Lazaryan A, et al. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar study. Blood. 2021;138:2278–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wolff D, Cutler C, Lee S, Pusic I, Bittencourt H, White J, et al. Safety and efficacy of axatilimab at 3 different doses in patients with chronic graft-versus-host disease (AGAVE-201). Blood. 2023;142:1. https://doi.org/10.1182/blood-2023-186963.

    Article  Google Scholar 

  10. Wolff D, Cutler C, Lee S, Pusic I, Bittencourt H, White J, et al. Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2024;391:1002–14. https://doi.org/10.1056/NEJMoa2401537. PMID: 39292927.

    Article  CAS  PubMed  Google Scholar 

  11. Fatoum H, Zeiser R, Hashmi SK. A personalized, organ-based approach to the treatment of chronic steroid-refractory graft-versus-host disease. Blood Rev. 2023, 101142. https://doi.org/10.1016/j.blre.2023.101142.

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Authors and Affiliations

  1. The Ohio State University Comprehensive Cancer Center, Division of Hematology, Columbus, USA

    Jean Caputo, Sarah Wall, Sumithira Vasu, Sam L. Penza & Hannah K. Choe

  2. The Ohio State University College of Medicine, Columbus, USA

    Ayush Peddireddi

  3. The Ohio State University Medical Center, Division of Pulmonology, Columbus, USA

    Kevin Ho & Vincent Esguerra

  4. The Ohio State University Medical Center, Division of Dermatology, Columbus, USA

    Benjamin H. Kaffenberger

Authors
  1. Jean Caputo
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  2. Ayush Peddireddi
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  3. Sarah Wall
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  4. Sumithira Vasu
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  5. Sam L. Penza
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  6. Kevin Ho
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  7. Vincent Esguerra
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  8. Benjamin H. Kaffenberger
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  9. Hannah K. Choe
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Contributions

JC completed data collection, data analysis, and drafted the manuscript. AP completed data collection, data analysis, and drafted the manuscript. SW assisted with data interpretation, reviewed, and edited the manuscript. SV assisted with data interpretation, reviewed, and edited the manuscript. SP assisted with data interpretation, reviewed, and edited the manuscript. KH assisted with data interpretation, reviewed, and edited the manuscript. VE assisted with data interpretation, reviewed, and edited the manuscript. BK assisted with data interpretation, reviewed, and edited the manuscript. HC conceptualized the project, design, and methodologies, assisted with data analysis, reviewed, and edited the manuscript.

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Correspondence to Jean Caputo.

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Caputo, J., Peddireddi, A., Wall, S. et al. Combination ruxolitinib, belumosudil, and axatilimab yields clinically significant symptomatic improvements in treatment-refractory chronic GVHD. Bone Marrow Transplant 61, 121–123 (2026). https://doi.org/10.1038/s41409-025-02764-2

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