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Second- and third-generation tyrosine kinase inhibitors for Philadelphia-positive adult acute lymphoblastic leukemia relapsing post allogeneic stem cell transplantation—a registry study on behalf of the EBMT Acute Leukemia Working Party

Bone Marrow Transplantation volume 56, pages 1190–1199 (2021)Cite this article

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Abstract

Second- and third-generation tyrosine kinase inhibitors (TKI) play an important role in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, data on feasibility and efficacy of using these drugs for persisting or relapsed Ph + ALL after allogeneic stem cell transplantation (alloSCT) are scarce. Based on the EBMT Acute Leukemia Working Party registry, we evaluated the use of second-/third-generation TKI in 140 patients with Ph + ALL, suffering from measurable residual disease (MRD, n = 6), molecular relapse (MRel, n = 23), or hematological relapse (HRel, n = 111) following alloSCT. Treatment included dasatinib in 104, nilotinib in 18, or ponatinib in 18 patients. Forty-nine patients received TKI monotherapy, while 91 received additional treatment. Toxicity of second-/third-generation TKI post alloSCT was comparable to pretransplant use and could be managed with dose reduction or temporary discontinuation. Response rates were 71% (overall) and 61% (following TKI monotherapy). For the entire cohort, 2- and 5-year overall survival (OS) was 49% and 33%, respectively. OS was comparable among patients treated for persisting MRD/MRel and HRel. Among patients treated with TKI monotherapy, 2- and 5-year OS was 38% and 33%, respectively. The data underscore that second-/third-generation TKI are important compounds for the management of active Ph + ALL post alloSCT.

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Fig. 1: Consort diagram of the study.
Fig. 2: Response and outcome for the entire cohort (n = 140).
Fig. 3: Response by type of TKI.
Fig. 4: Response and outcome for the cohort treated with TKI monotherapy (n = 49).

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Acknowledgements

We owe thanks to all the contributing centers.

Author information

Authors and Affiliations

  1. Department Hematology and Oncology, Medical Faculty, University of Augsburg, Augsburg, Germany

    Klaus Hirschbühl & Christoph Schmid

  2. Service d’Hématologie et de Thérapie cellulaire, Hôpital Saint Antoine, ALWP Office (EBMT), Paris, France

    Myriam Labopin, Mohamed Houhou & Mohamad Mohty

  3. Département d’Hématologie Clinique, CHU Lapeyronie, Montpellier, France

    Ludovic Gabellier

  4. Centre Hospitalier Lyon Sud, Service Hematologie, Lyon, France

    Hélène Labussière-Wallet

  5. Nouvel Hopital Civil, Strasbourg, France

    Bruno Lioure

  6. Department of Bone Marrow Transplantation, University Hospital Essen, Essen, Germany

    Dietrich Beelen

  7. Department of Hematology, Erasmus MC Cancer Institute University Medical Center Rotterdam, Rotterdam, The Netherlands

    Jan Cornelissen

  8. Abteilung Hämatologie und Onkologie, Universitätsklinikum Göttingen, Göttingen, Germany

    Gerald Wulf

  9. Department of Hematology/Oncology, Charles University Hospital, Pilsen, Czech Republic

    Pavel Jindra

  10. Department of Hematology, Centre Henri Becquerel, Rouen, France

    Hervé Tilly

  11. Department of Hematology, University Hospital of Basel, Basel, Switzerland

    Jakob Passweg

  12. HUCH Comprehensive Cancer Center, Stem Cell Transplantation Unit, Helsinki, Finland

    Riita Niittyvuopio

  13. Universitätsklinikum Frankfurt, Medizinische Klinik II, Frankfurt, Germany

    Gesine Bug

  14. Department of Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer and Tel-Aviv University, Tel Aviv, Israel

    Arnon Nagler

  15. Department of Bone Marrow Transplantation and Oncology/Hematology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland

    Sebastian Giebel

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  1. Klaus Hirschbühl
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Correspondence to Christoph Schmid.

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Hirschbühl, K., Labopin, M., Houhou, M. et al. Second- and third-generation tyrosine kinase inhibitors for Philadelphia-positive adult acute lymphoblastic leukemia relapsing post allogeneic stem cell transplantation—a registry study on behalf of the EBMT Acute Leukemia Working Party. Bone Marrow Transplant 56, 1190–1199 (2021). https://doi.org/10.1038/s41409-020-01173-x

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