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First-line steroid-free systemic treatment of acute and chronic graft-versus-host disease after novel prophylaxis regimens

Abstract

In the early randomized trials the efficacy of calcineurin inhibitors (CNI) in the treatment of graft-versus-host disease (GVHD) was comparable to corticosteroids (CS), but these results became obsolete with the introduction of CNIs in prophylaxis. Recently several effective CNI-free GVHD prophylaxis regimens were introduced based on posttransplantation cyclophosphamide (PTCY) and αβ ex vivo T-cell depletion (αβ-TCD). Among patients treated under these protocols 34 patients with grade II-IV acute (aGVHD) and 40 with moderate and severe chronic (cGVHD) disease were treated with CNIs or other CS-free regimens as the first line. Overall response rate (ORR) was significantly higher in cGVHD than in aGVHD: 80% (95% CI 68–92) vs 47% (95% CI 30–64%), p = 0.0031. In aGVHD it was almost completely restricted to isolated stage III skin GVHD. In cGVHD patients with moderate disease ORR was higher than in severe: 96% (95% CI 88–100%) vs 56% (95%CI 32–81%), p = 0.0022. Two-year overall survival was 76% (95% CI 58–87%) in aGVHD and 95% (95% CI 81–99%) in cGVHD. Failure-free survival was 21% (95% CI 9–37%) in aGVHD and 81% (95% CI 64–91%) in cGVHD. Patients responding to steroid-free regimens had lower use of systemic antibiotics (p = 0.0095), antifungals (p = 0.0319) and antivirals (p < 0.0001).

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Fig. 1: The response to immunosuppressive to 1st-line steroid-free treatments and 2nd line corticosteroids.
Fig. 2: Failure-free survival (left panel) and discontinuation of systemic immunosuppression (right panel).
Fig. 3: Individual organ responses at last follow up in chronic graft-versus-host disease patients treated with steroid-free regimens in the 1st line.

Data availability

Primary study data is available through request to Ethical Committee of Pavlov University according to standard operating procedures, e-mail: spbgmutrials@yandex.ru.

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Acknowledgements

We acknowledge the significant input in this work and support of this steroid-free approach of our former director, Boris Afanasyev, who passed away in 2020. We thank Michael Maschan for organizing multicenter validation of αβ-TCD prophylaxis.

Funding

This study is supported by Russian Science Fund grant 17-75-20145-P.

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IM: conceptualization, methodology, project administration, writing - original draft, visualization, funding acquisition; MB: formal analysis, writing - original draft, AD, AS, YV: investigation, data curation; EM: methodology, writing - review & editing; SB: methodology, writing - review & editing; AK: supervision, writing - review & editing.

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Correspondence to Ivan Moiseev.

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Moiseev, I., Barabanshikova, M., Dotsenko, A. et al. First-line steroid-free systemic treatment of acute and chronic graft-versus-host disease after novel prophylaxis regimens. Bone Marrow Transplant (2022). https://doi.org/10.1038/s41409-022-01879-0

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