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The role of checkpoint blockade after allogeneic stem cell transplantation in diseases other than Hodgkin’s Lymphoma

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Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment option for many malignant high-risk hematological diseases. The Graft-vs.-Tumor (GvT) effect is the major hallmark of this treatment approach. However, disease relapse remains a major limitation. Boosting the GvT effect by checkpoint inhibitors (CI) is an attractive option in this desperate situation although potentially triggering Graft-vs.-Host Disease (GvHD). Early reports in patients with Hodgkin’s lymphoma support the idea that CI therapy after HSCT is feasible and effective. We have retrospectively analyzed CI therapy for treatment of disease recurrence after allo-HSCT other than Hodgkin’s lymphoma including 21 patients from eight German transplant centers. The median follow-up was 59 days. The overall response rate (ORR) was 43%. Patients receiving donor lymphocyte infusion (DLI) in combination with CI had superior response (ORR 80%). Severe acute GvHD grade III–IV and moderate to severe chronic GvHD were observed in 29% of all patients. Taken together, CI therapy in relapsed patients after HSCT, especially in combination with DLI, is effective but induces severe GvHD in a considerable proportion of patients. Thus, prospective trials or EBMT registry-based validation of different dosing and application schedules including immunosuppressive regimens in those patients are urgently needed.

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Author notes

  1. These authors contributed equally: Tobias A. W. Holderried, Alessia Fraccaroli, Johanna Tischer, Dominik Wolf

Authors and Affiliations

  1. Department of Hematology, Oncology and Rheumatology, University Hospital Bonn, Bonn, Germany

    Tobias A. W. Holderried, Martin Schumacher, Annkristin Heine, Peter Brossart & Dominik Wolf

  2. Department of Medicine III, Hematopoietic Stem Cell Transplantation, University Hospital, LMU Munich, Munich, Germany

    Alessia Fraccaroli, Michael von Bergwelt-Baildon & Johanna Tischer

  3. Department of Bone Marrow Transplantation, University Hospital of Münster, Münster, Germany

    Matthias Stelljes

  4. Department of Internal Medicine III, Hematology and Oncology, University Hospital Regensburg, Regensburg, Germany

    Sebastian Klobuch

  5. Department of Stem Cell Transplantation, University Hospital Eppendorf, Hamburg, Germany

    Nicolaus Kröger

  6. Department of Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Petya Apostolova, Jürgen Finke & Robert Zeiser

  7. Department of Hematology and Oncology, Medical Center, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany

    Thomas Heinicke

  8. Medizinische Fakultät Carl-Gustav-Carus der Technischen Universität, Medizinische Klinik und Poliklinik I, University Hospital Carl-Gustav-Carus, Dresden, Germany

    Martin Bornhäuser

  9. UKIM 5, Medical University Innsbruck, Innsbruck, Austria

    Dominik Wolf

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  1. Tobias A. W. Holderried
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Correspondence to Johanna Tischer or Dominik Wolf.

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Holderried, T.A.W., Fraccaroli, A., Schumacher, M. et al. The role of checkpoint blockade after allogeneic stem cell transplantation in diseases other than Hodgkin’s Lymphoma. Bone Marrow Transplant 54, 1662–1667 (2019). https://doi.org/10.1038/s41409-019-0498-0

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