Medicine (RMH) - Research Publications

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    Recommendation for TP53 mutation testing in newly diagnosed mantle cell lymphoma: a statement from working groups sponsored by the Victorian Comprehensive Cancer Centre
    Tam, CS ; Gregory, GP ; Ku, M ; Fleming, S ; Handunnetti, SM ; Lee, D ; Walker, P ; Perkins, A ; Lew, TE ; Sirdesai, S ; Chua, CC ; Gilbertson, M ; Lasica, M ; Anderson, MA ; Renwick, W ; Grigg, A ; Patil, S ; Opat, S ; Friebe, A ; Cooke, R ; De Boer, J ; Spencer, A ; Ritchie, D ; Agarwal, R ; Blombery, P (WILEY, 2022-07)
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    T-Cell Replete Allogeneic Stem Cell Transplant Is an Effective Treatment Option for Patients with TP53 mutated Mantle Cell Lymphoma
    Scheffer Cliff, ER ; Lew, TE ; Blombery, P ; Dickinson, M ; Tam, CS ; Seymour, JF ; Bajel, A ; Ritchie, DS ; Khot, A (Elsevier BV, 2021-03)
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    Immune recovery in patients with mantle cell lymphoma receiving long-term ibrutinib and venetoclax combination therapy
    Davis, JE ; Handunnetti, SM ; Ludford-Menting, M ; Sharpe, C ; Blombery, P ; Anderson, MA ; Roberts, AW ; Seymour, JF ; Tam, CS ; Ritchie, DS ; Koldej, RM (AMER SOC HEMATOLOGY, 2020-10-13)
    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.