Immune recovery in patients with mantle cell lymphoma receiving long-term ibrutinib and venetoclax combination therapy.

Autor:	Davis JE; ACRF Translational Research Laboratory, Royal Melbourne Hospital, Melbourne, VIC, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia., Handunnetti SM; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.; Department of Clinical Haematology, Peter MacCallum Cancer Centre-Royal Melbourne Hospital, Melbourne, VIC, Australia., Ludford-Menting M; ACRF Translational Research Laboratory, Royal Melbourne Hospital, Melbourne, VIC, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia., Sharpe C; ACRF Translational Research Laboratory, Royal Melbourne Hospital, Melbourne, VIC, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia., Blombery P; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.; Department of Clinical Haematology, Peter MacCallum Cancer Centre-Royal Melbourne Hospital, Melbourne, VIC, Australia.; Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; and., Anderson MA; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.; Department of Clinical Haematology, Peter MacCallum Cancer Centre-Royal Melbourne Hospital, Melbourne, VIC, Australia.; Division of Cancer and Haematology, Walter and Eliza Hall Institute, Melbourne, VIC, Australia., Roberts AW; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.; Department of Clinical Haematology, Peter MacCallum Cancer Centre-Royal Melbourne Hospital, Melbourne, VIC, Australia.; Division of Cancer and Haematology, Walter and Eliza Hall Institute, Melbourne, VIC, Australia., Seymour JF; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.; Department of Clinical Haematology, Peter MacCallum Cancer Centre-Royal Melbourne Hospital, Melbourne, VIC, Australia., Tam CS; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.; Department of Clinical Haematology, Peter MacCallum Cancer Centre-Royal Melbourne Hospital, Melbourne, VIC, Australia., Ritchie DS; ACRF Translational Research Laboratory, Royal Melbourne Hospital, Melbourne, VIC, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.; Department of Clinical Haematology, Peter MacCallum Cancer Centre-Royal Melbourne Hospital, Melbourne, VIC, Australia., Koldej RM; ACRF Translational Research Laboratory, Royal Melbourne Hospital, Melbourne, VIC, Australia.; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2020 Oct 13; Vol. 4 (19), pp. 4849-4859.
DOI:	10.1182/bloodadvances.2020002810
Abstrakt:	Combination venetoclax plus ibrutinib for the treatment of mantle cell lymphoma (MCL) has demonstrated efficacy in the relapsed or refractory setting; however, the long-term impact on patient immunology is unknown. In this study, changes in immune subsets of MCL patients treated with combination venetoclax and ibrutinib were assessed over a 4-year period. Multiparameter flow cytometry of peripheral blood mononuclear cells showed that ≥12 months of treatment resulted in alterations in the proportions of multiple immune subsets, most notably CD4+ and CD8+ effector and central memory T cells and natural killer cells, and normalization of T-cell cytokine production in response to T-cell receptor stimulation. Gene expression analysis identified upregulation of multiple myeloid genes (including S100 and cathepsin family members) and inflammatory pathways over 12 months. Four patients with deep responses stopped study drugs, resulting in restoration of normal immune subsets for all study parameters except myeloid gene/pathway expression, suggesting long-term combination venetoclax and ibrutinib irreversibly affects this population. Our findings demonstrate that long-term combination therapy is associated with immune recovery in MCL, which may allow responses to subsequent immunotherapies and suggests that this targeted therapy results in beneficial impacts on immunological recovery. This trial was registered at www.clinicaltrials.gov as #NCT02471391. (© 2020 by The American Society of Hematology.)
Databáze:	MEDLINE
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