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Transplant Toxicities

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 51, pages 89–95 (2016)Cite this article

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Abstract

Elevated serum ferritin contributes to treatment-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The multicenter DE02 trial assessed the safety, efficacy and impact of deferasirox on iron homeostasis after allogeneic HSCT. Deferasirox was administered at a starting dose of 10 mg/kg per day to 76 recipients of allogeneic HSCT, with subsequent dose adjustments based on efficacy and safety. Deferasirox was initiated at a median of 168 days after HSCT, with 84% of patients still on immunosuppression. Baseline serum ferritin declined from 2045 to 957 ng/mL. Deferasirox induced a negative iron balance in 84% of patients. Hemoglobin increased in the first 3 months, and trough serum cyclosporine levels were stable. Median exposure was 330 days, with a median compliance rate of >80%. The most common investigator-reported drug-related adverse events (AEs) were increased blood creatinine (26.5%), nausea (9.0%) and abdominal discomfort (8.3%). Fifty-four (71.1%) patients experienced drug-related AEs, which occasionally resulted in discontinuation (gastrointestinal (n=6), skin (n=3), elevated transaminases (n=1) and creatinine (n=1)). The incidence of AEs appeared to be dose related, with 7.5 mg/kg per day being the best-tolerated dose. Low-dose deferasirox is an effective chelation therapy after allogeneic HSCT, with a manageable safety profile, even in patients receiving cyclosporine.

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Acknowledgements

This study was funded by Novartis Pharma AG. We thank Rebecca Helson and Catherine Risebro of Mudskipper Business Ltd for medical editorial assistance. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals.

Author contributions

NJ: Trial conduct and manuscript writing. GB, NK, UP, MS, KdH and DN: Trial conduct. KH: Data collection. SA and MUM: Hepcidin analysis. KL: Data collection and monitoring. SA and OL: Study design, protocol writing. HKA-A: Study design, protocol writing, trial conduct and manuscript writing. All authors participated in data interpretation and critical review of the manuscript, approved the manuscript and the decision to submit for publication.

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Authors and Affiliations

  1. Department of Hematology/Oncology, University Hospital of Leipzig, Leipzig, Germany

    N Jaekel, K Hubert, D Niederwieser & H K Al-Ali

  2. Novartis Pharma GmbH, Nürnberg, Germany

    K Lieder, S Albrecht & O Leismann

  3. Medizinische Klinik II, University Hospital Frankfurt, Frankfurt am Main, Germany

    G Bug

  4. University Hospital Hamburg, Hamburg, Germany

    N Kröger

  5. University of Dresden, Dresden, Germany

    U Platzbecker

  6. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    M Stadler

  7. University of Kiel, Kiel, Germany

    K de Haas

  8. Molecular Medicine Partnership Unit and Department of Pediatric Oncology, Hematology and Immunology, University Clinic of Heidelberg, Heidelberg, Germany

    S Altamura & M U Muckenthaler

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  1. N Jaekel
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Correspondence to H K Al-Ali.

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Competing interests

NJ, KH, MS, KdH, SA: None declared. GB: Research funding, travel grants and honoraria, Novartis. NK: Research funding, Novartis. UP: Research funding and honoraria, Novartis. MUM: Consulting fees and payment for the hepcidin analyses, Novartis. DN: Research funding and honoraria, Novartis. HKA-A: Research funding and honoraria, Novartis. KL, SA, OL: Employment, Novartis.

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Jaekel, N., Lieder, K., Albrecht, S. et al. Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 51, 89–95 (2016). https://doi.org/10.1038/bmt.2015.204

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