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• W4382806870 abstract "Atezolizumab/Bevacizumab (AtezoBv) is a reference EMA-approved combination superior to sorafenib in aHCC. Nonetheless, primary resistance rate is as high as 20% and no circulating biomarkers of treatment benefit prediction are known. Flow-cytometry allows for a non-invasive, dynamic evaluation of peripheral immunitary status. In aHCC, it successfully stratified anti-PDL1 plus anti-CTLA4 treatment activity, whilst this is the first report of its application to AtezoBv. Consecutive aHCC patients treated with AtezoBv at Pisa Medical Oncology were prospectively enrolled from March 2021 to August 2022. Six-ml EDTA whole-blood were drawn predose at baseline (B), early on-treatment (E, cycles2/3 day1), and at first radiological evaluation (R). Four Flow-cytometry assays were designed to quantify the following cell subsets: T, B, NK, CD4+, CD8+, TIM+/LAG+/Ki67+ CD4+ and CD8+, T regulatory (TReg), classical and alternative monocytes, and neutrophils. Patients were dichotomized into primary-progressors (PP, if progressive disease was evident at first CT scan) and disease-controlled (DC, if partial response or stable disease was achieved). A cohort of healthy controls (HC) was enrolled. Distribution of immune cells concentration (cells/uL) was compared between HC and aHCC and between PP and DC with independent samples T-test or Mann-Whitney test (if normally and non-normally distributed, respectively). Cell subsets’ longitudinal trend from B to E to R was compared within and among the two groups (PP and DC) with repeated measures ANOVA. Progression-free survival (PFS) and overall-survival (OS) were estimated with Kaplan Meier curves. Eleven aHCC patients (4 PP and 7 DC) and 9 HC were evaluated. AHCC cohort showed a prevalence of male gender (63.6%) and of extra-hepatic spread or macro-vascular invasion (72.7%), a median age of 68.9 (42,1-81,0) years and an even distribution between viral (HCV and/or HBV, 54.5%) and non-viral etiologies (dismetabolic or healthy livers, 45.5%). Compared to HC, aHCC patients had higher neutrophils-to-lymphocytes ratio (p=0.02), lower T (p=0.02), CD4+ (p=0.03), B (p < 0.01) and Ki67+CD8+ (p=0.05) cells, whilts higher LAG+CD4+ (p < 0.01) and LAG+CD8+ (p=0.03). Despite non-significantly different vs HC, TIM+CD4+ and TIM+CD8+ were positively correlated with LAG+ T lymphocytes (p for R2 0.04 and < 0.01, respectively) among aHCC. After treatment with AtezoBv, a DC rate of 63.7% was observed (2 PR and 5 SD) along with a PP rate of 36.3%, leading to a mPFS of 4,01 months (95% IC 2,27-10,56) and mOS of 13,03 months (95% IC 9,01-15,76; mOS for PP vs DC: 6.45 vs 15.76 months, p=0.08), at 11.09 months (95% IC 8,82-23,22) of median follow-up. Compared to DC, PP had lower NK at B (p=0.05) and E (p=0.03). Among PP, TReg increased from B to R (p=0.03), while NK increased from B to E (p=0.01), to R (p=0.03) in DC. A non-significant trend toward LAG+CD8+ decrease was seen from B to E to R in DC (3 subjects evaluable: 60.8 vs 22.1 vs 1.6 mean cells/uL). Despite hampered by low numerosity of the case-series, peripheral cells flow-cytometry identified aHCC patients as “immune down-regulated” if compared to HC, as known at tissue-level. Furthermore, NK and Treg dynamics might be a promising tool to predict AtezoBev activity." @default.
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• W4382806870 date "2023-06-01" @default.
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• W4382806870 title "P-54 Circulating immune cells as a tool to predict benefit from atezolizumab/bevacizumab in advanced hepatocellular carcinoma (aHCC)" @default.
• W4382806870 doi "https://doi.org/10.1016/j.annonc.2023.04.110" @default.
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