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Infections in steroid-refractory chronic graft versus host disease patients treated with ruxolitinib, ibrutinib, or belumosudil

Bone Marrow Transplantation volume 60, pages 1410–1412 (2025)Cite this article

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Chronic graft-versus-host disease (cGVHD) is a multi-organ disease that results from a combination of inflammation due to tissue injury by pre-transplant conditioning, T- and B-cell dysregulation, and aberrant tissue repair [1]. cGVHD remains a significant cause of transplant-related morbidity and mortality. Over half of patients develop steroid refractory-cGVHD (sr-cGVHD) requiring additional immunosuppressive therapies [2, 3], which may lead to significant toxicities including infections. Thirty-five percent of deaths among patients with cGVHD are attributable to infection [4].

Over the last decade, the U.S. Food and Drug Administration (FDA) has approved four new second and third-line drugs for the treatment of sr-cGVHD: Ibrutinib (2017), Belumosudil (2021), Ruxolitinib (2021), and most recently Axatilimab (2024) [5,6,7,8]. While randomized controlled trials reported infection risks, with the REACH3 trial reporting higher rates of infection in ruxolitinib-treated patients compared to controls, and the phase II trial of ibrutinib and ROCKSTAR trial of belumosudil providing descriptive reports [9,10,11]; real-world data on the risk of infection in patients with sr-cGVHD with these novel immunomodulatory agents are limited. Our study aims to characterize the incidence and outcomes of infection in patients with sr-cGVHD treated with ruxolitinib, ibrutinib, and belumosudil in a real-world setting.

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Fig. 1: Non-relapse mortality and overall survival post transplantation.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA

    Victoria Stepanyants

  2. Department of Biostatistics and Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA

    Hong Li

  3. Department of Hematology and Medical Oncology, Cleveland Clinic Cancer Institute, Cleveland, OH, USA

    Danielle Cenin, Jessi Edwards, Claudio Brunstein, Matt Kalaycio, Ronald Sobecks & Betty K. Hamilton

  4. Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, USA

    Craig S. Sauter

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  1. Victoria Stepanyants
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  8. Craig S. Sauter
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  9. Betty K. Hamilton
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Contributions

VS designed the study protocol, collected data, interpreted and performed statistical analysis, and wrote the manuscript. HL performed statistical analysis and critically reviewed the manuscript. DC and JE contributed to conception of study, designed the study protocol and critically reviewed the manuscript. CB, MK, RS, and CS contributed patients and critically reviewed the manuscript. BKH contributed patients, conceived the study, designed the study protocol, supervised data analysis and interpretation, and provided critical review of the manuscript.

Corresponding author

Correspondence to Betty K. Hamilton.

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Competing interests

The authors report the following conflicts of interest: Dr. Hamilton reports (ad hoc) advisory boards for Sanofi, Incyte, Maat; research funding from Incyte; adjudication committee with CSL Behring. The remaining authors have no relevant disclosures to report.

Ethics approval and consent to participate

This study was approved by the Cleveland Clinic Institutional Review Board, which deemed this study minimal risk research not requiring informed consent. All methods were performed in compliance with the relevant regulations, including the Declaration of Helsinki. No identifiable patient details are presented in this manuscript.

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Stepanyants, V., Li, H., Cenin, D. et al. Infections in steroid-refractory chronic graft versus host disease patients treated with ruxolitinib, ibrutinib, or belumosudil. Bone Marrow Transplant 60, 1410–1412 (2025). https://doi.org/10.1038/s41409-025-02690-3

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