Abstract
The aim of this retrospective study was to investigate the safety and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) in patients pre-treated with ibrutinib. Eligible were patients aged >18 years allotransplanted for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) after prior exposure to ibrutinib who were registered with the EBMT registry. Seventy patients (CLL 48, MCL 22) were included. At the time of alloHCT, 73% of the patients were ibrutinib responsive. All patients except one engrafted, and acute GVHD grade 2–4 (3–4) was observed in 49% (12%) of 68 evaluable patients. The cumulative incidence of chronic GVHD was 54% 1 year after transplant. In the CLL group, 12-month non-relapse mortality, relapse incidence (RI), progression-free survival (PFS), and overall survival (OS) were 10, 30, 60, and 72%, respectively, and in the MCL group 5, 19, 76, and 86%, respectively. Pre-transplant ibrutinib failure and poor performance status predicted inferior RI, PFS and OS in the CLL group. In conclusion, ibrutinib does not affect the safety of a subsequent alloHCT. While the relatively high post-transplant relapse risk in ibrutinib-exposed patients with CLL deserves further study, in patients with MCL consolidating disease responses to ibrutinib with alloHCT seems to be a promising option.
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Acknowledgements
The authors acknowledge all collaborating EBMT Investigators and Institutions that contributed cases to this study.
Author contributions
PD and MM: designed and performed research, analyzed data, and wrote the paper; SD: performed research, analyzed data; AB: designed and performed research, analyzed data; PB, MS, AN, CS, JC, DN, LM, EV, IS, HS, NA, JF, DR, PL, JP, MvG, ND, HL-W, TB, GW, WB, DB, SS, MC, MS, and CPF performed research; NK, SM, and JS designed and performed research.
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PD: Consultancy for AbbVie, Roche and Janssen; consultancy and speakers bureau for Gilead; speakers bureau for Kite Pharma. MM: Consultancy and Speakers bureau for Sanofi, MSD, Octapharma, Pfizer, MAATPharma, Novartis. CPF: Consultancy, speakers bureau and travel grants from Janssen. MvG: Consultancy for Gilead and Janssen; speakers bureau for Abbvie, Gilead, Janssen and Roche; Educational support from Gilead. TB: Consultancy for Riemser; travel grants from Astellas, Alexion, Celgene, Abbvie. SS: Consultancy, Speakers bureau, travel grants and research funding from AbbVie, Amgen, Celgene, Gilead, GSK, Roche, Janssen, Novartis, Pharmacyclics. SM: Speakers bureau for Roche; travel grant from Gilead. JS: Consultancy and Speakers bureau for AbbVie, Gilead, Janssen, Roche, Sanofi; research funding from Genzyme, Sanofi, GSK, Novartis, Abbvie. The remaining authors declare that they have no conflict of interest.
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Dreger, P., Michallet, M., Bosman, P. et al. Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties. Bone Marrow Transplant 54, 44–52 (2019). https://doi.org/10.1038/s41409-018-0207-4
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DOI: https://doi.org/10.1038/s41409-018-0207-4
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