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Nilotinib efficacy and safety as salvage treatment following imatinib intolerance and/or inefficacy in steroid refractory chronic graft-versus-host-disease (SR-cGVHD): a prospective, multicenter, phase II study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

Bone Marrow Transplantation volume 58, pages 401–406 (2023)Cite this article

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Abstract

Imatinib is used for patients with SR-cGVHD. However, in 50% of cases imatinib is discontinued due to intolerance or inefficacy. In order to investigate nilotinib’s role as salvage therapy in those patients, we conducted a prospective, multicenter, phase II study. (NCT02891395). Patients with SR-cGVHD were included to receive imatinib. Patients who stopped imatinib due to intolerance or inefficacy switched to Nilotinib. The primary endpoint was defined as the week-12 response rate to Nilotinib. The response was considered successful if superior to the 30% endpoint. Sixty-two patients started the IM-phase. Fourteen patients (22%) discontinued imatinib before week 12 due to: cGVHD progression (10%) or TKI-class-specific intolerance (12%). At week 12, we observed complete remission in 13 patients (21%) and partial response in 8 patients (13%). Twenty-nine patients switched to Nilotinib. Nilotinib response at week-12 was observed in 6 patients (21%) while 23 patients (79%) discontinued Nilotinib due to intolerance/cGVHD progression. The primary endpoint was not reached. This prospective study confirmed the efficacy of imatinib in patients with steroid refractory cGVHD. It failed to demonstrate the efficacy of nilotinib as a salvage therapy in patients who were intolerant/unresponsive to imatinib.

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Fig. 1: Flowchart of the imatinib mesylate (IM) phase.
Fig. 2: Flowchart of the nilotinib (Ni) phase.
Fig. 3: Overall survival.
Fig. 4: Best response duration in the imatinib mesylate group.
Fig. 5: Best response duration in the nilotinib group.

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Data availability

The dataset generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author information

Author notes

  1. These authors contributed equally: Micha Srour, Tamim Alsuliman.

Authors and Affiliations

  1. Service maladie du sang, centre hospitalier universitaire de Lille, 59000, Lille, France

    Micha Srour, Valerie Coiteux, Ibrahim Yakoub-Agha & Leonardo Magro

  2. Sorbonne University, Paris, France

    Tamim Alsuliman

  3. Service d’Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, AP-HP, Paris, France

    Tamim Alsuliman

  4. INSERM, UMRs 938, Paris, France

    Tamim Alsuliman

  5. CHU Lille, Department of Biostatistics, F59000, Lille, France

    Julien Labreuche

  6. CHU Grenoble Alpes - Université Grenoble Alpes, Service d’Hématologie, Grenoble, France

    Claude-Eric Bulabois

  7. Hematology department, CHU de Nantes, Nantes, France

    Patrice Chevallier

  8. Hopital Jean Minjoz, Besancon, France

    Etienne Daguindau

  9. CHU, Bordeaux, France

    Edouard Forcade

  10. Department of Clinical Hematology, Angers University Hospital, Angers, France

    Sylvie François

  11. Hematology Department, Brest University Hospital, Brest, France

    Gaelle Guillerm

  12. Département d’Hématologie Clinique, CHU Limoges, Limoges, France

    Pascal Turlure

  13. Department of Hematology, CHU of Liege and University of Liege, 4000, Liege, Belgium

    Yves Beguin

  14. CHU de Lille, Univ Lille, INSERM U1286, Infinite, 59000, Lille, France

    Ibrahim Yakoub-Agha

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Contributions

IYA, LM, TA, and MS have contributed to the project conceptualization. TA and MS have contributed equally to this paper preparation and drafting. IYA have supervised the project and contributed to the finalization of the paper. JL have accomplished the statistical analysis. All authors read and approved the final draft.

Corresponding author

Correspondence to Ibrahim Yakoub-Agha.

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Competing interests

TA received honorarium from Biotest France SAS, out of the current paper. ED received honorarium from SOBI board, out of the current paper. MS, GG, SF, JL, PT, PC, has no competing interests. IYA, LM, VA, EF, CEB, YB, received honorarium from NOVARTIS. This trial received an unrestricted fund from NOVARTIS.

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Srour, M., Alsuliman, T., Labreuche, J. et al. Nilotinib efficacy and safety as salvage treatment following imatinib intolerance and/or inefficacy in steroid refractory chronic graft-versus-host-disease (SR-cGVHD): a prospective, multicenter, phase II study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Bone Marrow Transplant 58, 401–406 (2023). https://doi.org/10.1038/s41409-022-01898-x

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