Immune recovery in patients with mantle cell lymphoma receiving long-term ibrutinib and venetoclax combination therapy
AuthorDavis, JE; Handunnetti, SM; Ludford-Menting, M; Sharpe, C; Blombery, P; Anderson, MA; Roberts, AW; Seymour, JF; Tam, CS; Ritchie, DS; ...
Source TitleBlood Advances
PublisherAMER SOC HEMATOLOGY
University of Melbourne Author/sLudford-Menting, Mandy; Seymour, John; Tam, Constantine; Ritchie, David; Roberts, Andrew; Davis, Joanne; Koldej, Rachel; Handunnetti, Sasanka; Anderson, Mary Ann; Blombery, Piers
AffiliationMedicine and Radiology
Centre for Cancer Research
Sir Peter MacCallum Department of Oncology
Medical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsDavis, J. E., Handunnetti, S. M., Ludford-Menting, M., Sharpe, C., Blombery, P., Anderson, M. A., Roberts, A. W., Seymour, J. F., Tam, C. S., Ritchie, D. S. & Koldej, R. M. (2020). Immune recovery in patients with mantle cell lymphoma receiving long-term ibrutinib and venetoclax combination therapy. BLOOD ADVANCES, 4 (19), pp.4849-4859. https://doi.org/10.1182/bloodadvances.2020002810.
Access StatusAccess this item via the Open Access location
Open Access URLPublished version
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.
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