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Ibrutinib for steroid refractory chronic graft-versus-host disease: therapeutic efficiency can be limited by increased risk of fungal infection

Bone Marrow Transplantation volume 56, pages 2034–2037 (2021)Cite this article

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Steroid refractory chronic graft-versus-host disease (SR-cGvHD) remains a leading cause for late non-relapse mortality post allogeneic stem cell transplantation (alloSCT), which also adversely affects the quality of life in long-term surviving patients. Despite the advances in supportive care during and post-alloSCΤ and the progress in understanding of GvHD pathophysiology, for SR-cGVHD no standard therapy exists and not long ago, the available treatment options were limited and grossly ineffective [1]. It is well documented that both T- and B-cells orchestrate the pathogenesis and progress of cGvHD [2]. Bruton tyrosine kinase (BTK) inhibitors demonstrating unique activities by downregulating the B-cell survival while concurrently inhibit the alloreactive T-cell activation, could be an appealing agent for cGvHD management [3, 4]. Recently, Ibrutinib, a first generation BTK-inhibitor, has been approved by the US Food and Drug Administration for the treatment of SR-cGvHD, showing remarkable efficacy and acceptable toxicity in a phase 1b/2 study [5]. However, the real-world data from its clinical use are still limited.

Following our Institutional Review Board approval, we retrospectively reviewed the medical records of 11 patients with median age of 28.6 years (range, 17–62) who received Ibrutinib as ≥2 line treatment for severe SR-cGvHD. All had received peripheral blood stem cells from full matched sibling (n = 10) or haploidentical (n = 1) donors after myeloablative (n = 8) or reduced intensity conditioning (n = 3) regimens. Acute GvHD was preceded in 7 (de-novo = 3, induced = 4) patients. The involved organs were skin (n = 11), oral mucosal (n = 9), liver (n = 6), lungs (n = 5), gastrointestinal tract (n = 2), musculoskeletal system (n = 2). Five patients had 3 organs involvement, four had 4 organs, one had 6 organs and one had 2 organs involvement. Nine patients (80%) received Ibrutinib as ≥3rd line while two as 2nd line of treatment, with a starting dose of 140 or 280 mg once daily and if it was well tolerated, the dose was escalated to the maximum of 420 mg (Table 1). During the treatment, all patients received prophylaxis against bacteria, viruses, and fungi as per standard recommendations.

Table 1 Patient characteristics and outcome.
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Authors and Affiliations

  1. Adults Hematology & Stem Cell Transplantation Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia

    Panayotis Kaloyannidis, Ahmed Ayyad, Zakaria Bahaliwah, Belal Blowi, Wael Alanazi, Zahra Al Shammasi & Hani Al Hashmi

  2. Clinical Pharmacy Service, King Fahad Specialist Hospital, Dammam, Saudi Arabia

    Hamdi Elsoudi & Ibrahim Ibrahim

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  1. Panayotis Kaloyannidis
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Correspondence to Panayotis Kaloyannidis.

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Kaloyannidis, P., Ayyad, A., Bahaliwah, Z. et al. Ibrutinib for steroid refractory chronic graft-versus-host disease: therapeutic efficiency can be limited by increased risk of fungal infection. Bone Marrow Transplant 56, 2034–2037 (2021). https://doi.org/10.1038/s41409-021-01318-6

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