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Clinical outcomes of third-line therapy for aGvHD with gastrointestinal involvement after steroids and ruxolitinib failure

Bone Marrow Transplantation (2026)Cite this article

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Abstract

CHRONOS is a multicenter, retrospective, cohort study involving acute graft-versus-host disease (aGvHD) adult patients with gastrointestinal (GI) symptoms, steroid- and ruxolitinib refractory, who initiated third-line therapy between 30 May 2019 and 30 September 2024. Primary endpoints were all-organ overall response rate (ORR) and GI-specific ORR (GI-ORR) around 28 days after treatment initiation. Secondary endpoints included duration of response, real-world progression-free survival (rwPFS) of underlying malignancy, and overall survival (OS). Fifty-nine patients from 16 sites in Europe were included. On Day 28, ORR was 36% (95% CI: 24–49%), GI-ORR was 37% (95% CI: 25–51%); 29% (95% CI: 11–49%) of responders lost response within 30 days, and 52% (95% CI: 29–72%) within 90 days. Median rwPFS and median OS were both 86 days (95% CI: 54–128 days). Median OS was higher in responders than in non-responders (186 versus 45 days). Over the 12-month follow-up period, 41 patients died, mainly due to aGvHD progression (n = 25), and infectious complications (n = 9). Within 3 months, Grade ≥ 2 infectious events occurred in 51% of patients; Grade 3–4 thrombocytopenia and neutropenia in 64% and 32%, respectively. These findings demonstrate limited effectiveness of third-line therapy in this cohort of steroid- and ruxolitinib-refractory aGvHD patients with GI symptoms.

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Fig. 1: Cumulative incidence of loss of response.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank Pierre CLERSON (Soladis Clinical Studies) for medical writing support and Marie-Blanche ONSELAER (Soladis Clinical Studies) for scientific writing support.

Funding

MaaT Pharma.

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Authors and Affiliations

  1. Ordensklinikum Linz Elisabethinen, Hematology Department, Linz, Austria

    Johannes Clausen & Anna Bauhofer

  2. Instituto de Biomedicina de Sevilla (IBIS / CSIC), Hematology Department, Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Seville, Spain

    José Antonio Pérez Simón

  3. CHU Grenoble Alpes - Université Grenoble Alpes, Hematology Department, Grenoble, France

    Martin Carré

  4. Gustave Roussy Cancer Campus Grand Paris, Hematology Department, Villejuif, France

    Cristina Castilla-Llorente

  5. Hôpital Saint-Louis, APHP, Hematology Department, Paris, France

    David Michonneau

  6. Algemeen Ziekenhuis Sint-Jan Brugge, Brugge, Belgium

    Alexander Schauwvlieghe

  7. Hospital Universitari i Politècnic La Fe, Hematology Department, Valencia, Spain

    Pedro Asensi Cantó

  8. CHU Angers, Hematology Department, Angers, France

    Sylvie François

  9. CHU de Montpellier, Hôpital Saint Eloi, Service d’hématologie clinique, Montpellier, France

    Ludovic Gabellier

  10. Hematology Department, Complejo Asistencial Universitario de Salamanca-IBSAL; Departamento de Medicina, Universidad de Salamanca, Centro de Investigación del Cáncer-IBMCC, Salamanca, Spain

    Lucía López Corral

  11. Hospital Clínico Universitario, INCLIVA Research Institute, Hematology Department, Valencia, Spain

    Ana Benzaquén

  12. Hôpital Lyon Sud, HCL, Hematology Department, Pierre-Bénite, France

    Hélène Labussière-Wallet

  13. Department of Clinical Hematology and Cell Therapy. Saint-Etienne University Hospital, Saint-Étienne, France

    Jérome Cornillon

  14. Institut Paoli Calmettes, Hematology Department, Marseille, France

    Raynier Devillier

  15. CHU / IUCT-Oncopole, Hematology Department, Toulouse, France

    Anne Huynh

  16. Limoges University Hospital, Hematology Department, Limoges, France

    Pascal Turlure

  17. MaaT Pharma, Lyon, France

    Hervé Jullien de Pommerol, Marion Bruelle, Behzad Kharabi Masouleh & Emilie Plantamura

  18. Inovia Bio, London, UK

    Imi Faghmous

  19. Department of Clinical Hematology and Cellular Therapy, Saint-Antoine Hospital, AP-HP, Sorbonne University, INSERM UMR 938, Centre de Recherche Saint-Antoine, Paris, France

    Florent Malard & Mohamad Mohty

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Contributions

EP, FM, MM contributed to the conception of the study. EP, HJP, BKM, IF contributed to the design of the study, analysis and interpretation of the data. HJP supervised the project. HJP, FM, MM wrote and critically revised the manuscript. JC, JAPS, MC, CCL, DM, AS, PAC, SF, LG, LLC, A Benzaquen, HL-W, JC, RD, AH, PT, A Bauhofer, HPJ, MB contributed to the collection of data. All authors reviewed and approved the manuscript.

Corresponding authors

Correspondence to Florent Malard or Mohamad Mohty.

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Competing interests

JAPS received research grants from Sanofi, Incyte and Amge; consulting fees from Gilead, J&J, Novartis, BMS, Sanofi, Jazz pharmaceuticals, Incyte, GSK, Amgen; honoraria or travel support from Gilead, J&J, Novartis, BMS, Sanofi, Jazz pharmaceuticals, Incyte, GSK, Amgen, MDS. CCL received honoraria or travel support from Jazz pharmaceuticals. DM received research grants from Novartis, Sanofi, CSL Behring; consulting fees from Novartis, Incyte, Sanofi, Jazz pharmaceuticals; honoraria or travel support from Sanofi, Novartis, Jazz pharmaceuticals; fees for participation in review activities such as data monitoring boards or advisory boards from Incyte, Sanofi. AS received consulting fees from Alexion, Gilead, MaaT pharma, Novartis, Basilea, Sanofi. AS received honoraria from Pfizer satellite symposia, Pierre Fabre; fees for participation in review activities such as data monitoring boards or advisory boards from Alexion, Gilead, Maat Pharma, Novartis, Basilea, Sanofi. PAC received honoraria or travel support from Kite, Amgen, Macopharma, Gilead, Therakos, Novartis. LG received travel support from Gilead. LG received research grants and consulting fees from Grifols, Abbvie. RD received consulting fees from Sanofi, Novartis. AH received travel support from Sanofi, Novartis. FM received honoraria or travel support from Gilead, Sanofi, Novartis, BMS, Astrazeneca, Therakos, Priothera, MSD, Jazz pharmaceuticals. MM received research grants from Sanofi, Novartis, Janssen, Jazz pharmaceuticals; consulting fees from Adaptive Biotechnologies, Amgen, Astellas, BMS, GSK, Janssen, Jazz Pharmaceuticals, Novartis, Pfizer, Sanofi, Stemline, Takeda; honoraria from Adaptive Biotechnologies, Amgen, Astellas, BMS, GSK, Janssen, Jazz Pharmaceuticals, Novartis, Pfizer, Sanofi, Stemline, Takeda, MaaT pharma; fees for participation in review activities such as data monitoring boards or advisory board from Jenssen; holds a role on the board, society or committee of EBMT, IACH. HJP, IF, BKM, received consulting fees from Maat Pharma. BKM received travel support from Maat Pharma. MB, EP are employees and stockholders of MaaT Pharma. HJP is stockholder of MaaT Pharma. JC, MC, SF, LLC, PT, A Bauhofer and A Benzaquen declare no competing interests.

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Clausen, J., Pérez Simón, J.A., Carré, M. et al. Clinical outcomes of third-line therapy for aGvHD with gastrointestinal involvement after steroids and ruxolitinib failure. Bone Marrow Transplant (2026). https://doi.org/10.1038/s41409-026-02825-0

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