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Phase-1/-2 study of pomalidomide in chronic GvHD

Bone Marrow Transplantation volume 51, pages 612–614 (2016)Cite this article

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Chronic GvHD (cGvHD) is an important cause of post-transplant morbidity and mortality with an incidence of 40%–60%.1 Prednisone, alone or with calcineurin inhibitors, is the most commonly used therapy but the response rate is only ~50% and most subjects subsequently fail.2, 3 There is no standard therapy for failures and participation in clinical trials is recommended. Thalidomide is active in mouse models of cGvHD and tested for prevention and therapy of cGvHD in humans.4, 5, 6, 7, 8 However, doses expected to be effective were poorly tolerated because of somnolence, neuropathy and constipation. Pomalidomide is a new immune-modulating drug with 4000-fold greater inhibition of TNF-α relative to thalidomide. In randomized studies in persons with multiple myeloma, pomalidomide was well-tolerated at doses up to 4 mg/d and without the adverse effects associated with thalidomide.9 Several features of pomalidomide suggest it may be useful in treating cGvHD. Despite recent advances in understanding the disease processes,10 the pathogenesis of cGvHD is unknown. Consequently, it is impossible to predict the impact of pomalidomide on cGvHD except in a clinical trial.11

This was a single institution, open label, pilot study of safety and efficacy of pomalidomide in subjects with corticosteroid-refractory cGvHD (NCT00770757). Approval was obtained from the Institutional Review Board and subjects gave written informed consent. Eligible subjects were ⩾18 years old in complete haematologic remission following an allotransplant and with moderate or severe cGvHD. Subjects with overlap cGvHD were allowed on-study, whereas subjects with late-onset acute GvHD were excluded. Subjects must have failed high-dose corticosteroids (0.5 mg/kg/d prednisone for ⩾2 months) or second-line immune suppression. Subjects receiving corticosteroids at enrollment had to be on a stable or decreasing dose for ⩾2 months and no new immune suppressive drugs were allowed ⩽1 month before study entry. Extracorporeal photopheresis, if given, had to be completed ⩾3 months before study entry. Karnofsky performance score had to be ⩾60%, life-expectancy ⩾3 months, platelets ⩾75 × 10E+9/L, neutrophils ⩾1 × 10E+9/L, creatinine clearance ⩾50 mL/min, cardiac ejection fraction ⩾40% and no uncontrolled infections.

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Acknowledgements

Financial Disclosures: This study was supported in part by Celgene Corporation, Summit, NJ, USA.

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Author notes

  1. I Pusic and M P Rettig: These authors contributed equally to this work

Authors and Affiliations

  1. Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA

    I Pusic, M P Rettig, J F DiPersio, S Bauer & K McFarland

  2. Division of Experimental Medicine, Department of Medicine, Haematology Research Centre, Imperial College London, London, UK

    R P Gale

  3. Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    S Z Pavletic

Authors
  1. I Pusic
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Correspondence to I Pusic.

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RPG is a part-time employee of Celgene Corp. The remaining authors declare no conflict of interest.

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Pusic, I., Rettig, M., DiPersio, J. et al. Phase-1/-2 study of pomalidomide in chronic GvHD. Bone Marrow Transplant 51, 612–614 (2016). https://doi.org/10.1038/bmt.2015.298

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