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Corticosteroid replacement by ruxolitinib in patients with acute GVHD experiencing severe steroid-induced side effects

Bone Marrow Transplantation volume 55, pages 253–255 (2020)Cite this article

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Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has a great impact on morbidity and mortality. At present, the first-line therapy for aGVHD grade II–IV consists of high-dose corticosteroids, i.e., prednisolone or equivalent 2 mg/kg [1]. Currently, there is no second-line therapy registered for steroid-refractory aGVHD (SR-aGVHD), although there are several potential candidates under investigation including, α-1-antitrypsin, brentuximab vedotin, tociluzumab, vedolizumab, anti-CD3/CD7 immunotoxins, and ruxolitinib [2, 3]. Considering the deleterious effects associated with prolonged corticosteroid use, including infections, myopathy, diabetes mellitus, osteoporosis, and psychiatric disorders [4], the question arises whether one of these new therapies has the potential to replace corticosteroids as first-line therapy altogether. Thus far, this has not been studied and all of the aforementioned drugs have only been investigated in combination with corticosteroids [4, 5]. However, JAK-STAT inhibitors (Jakinibs), including ruxolitinib, have a largely similar and overlapping profile with regards to cytokine inhibition, albeit with considerably less off-target effects and potentially superior efficacy [6]. In our centre we have gained considerable experience with ruxolitinib as an adjunct to or replacement of corticosteroid therapy. Therefore, we wanted to evaluate the interchangeability of ruxolitinib and high-dose corticosteroids by evaluating the feasibility of rapid drug conversion in patients experiencing unacceptable side effects with corticosteroid therapy for aGVHD.

We performed a single center retrospective analysis in a cohort of 68 patients who had received ruxolitinib as part of the treatment of GVHD, mostly steroid-refractory acute and chronic GVHD, since 2015. In eight patients, ruxolitinib was started with the sole reason to replace prednisolone because of severe side effects. The goal was to taper the prednisolone to a daily dose of 5 mg (adrenal replacement dose) or less within 4 weeks in order to facilitate rapid resolution of side effects. Calcineurin inhibitor dose remained unchanged during the conversion to ruxolitinib. In the absence of guidelines tapering of ruxolitinib was left to the discretion of the treating physician. In general tapering was initiated after having achieved a persistent complete remission of the aGVHD and then the dose was reduced with 5 mg every 3–4 weeks. This retrospective study was approved by the Institutional Review Board at Radboud University Nijmegen Medical Center.

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  1. Department of Hematology, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, Netherlands

    Elizabeth A. de Kort, Suzanne van Dorp, Nicole M. A. Blijlevens & Walter J. F. M. van der Velden

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  1. Elizabeth A. de Kort
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Correspondence to Walter J. F. M. van der Velden.

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de Kort, E.A., van Dorp, S., Blijlevens, N.M.A. et al. Corticosteroid replacement by ruxolitinib in patients with acute GVHD experiencing severe steroid-induced side effects. Bone Marrow Transplant 55, 253–255 (2020). https://doi.org/10.1038/s41409-019-0526-0

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