Early kinetics of C reactive protein for cancer-agnostic prediction of therapy response and mortality in patients treated with immune checkpoint inhibitors: a multicenter cohort study
التفاصيل البيبلوغرافية
العنوان:
Early kinetics of C reactive protein for cancer-agnostic prediction of therapy response and mortality in patients treated with immune checkpoint inhibitors: a multicenter cohort study
Background C reactive protein (CRP) kinetics have recently been suggested as predictive biomarkers for the efficacy of immune checkpoint inhibitor (ICI) therapy in selected cancer types. The aim of this study was to characterize early CRP kinetics as a tumor-agnostic biomarker for ICI treatment outcomes.Methods In this multicenter retrospective cohort study, two independent cohorts of patients with various cancer types undergoing palliative ICI treatment at Austrian academic centers served as the discovery (n=562) and validation cohort (n=474). Four different patterns of CRP kinetics in the first 3 months of ICI therapy were defined (CRP-flare responders, CRP-responders, CRP non-responders, patients with all-normal CRP). Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were defined as coprimary endpoints. Univariable and multivariable logistic regression, landmark analysis and Cox regression including CRP kinetics as time-dependent variable were performed.Results The ORR in patients with all-normal CRP, CRP responders, CRP flare-responders and CRP non-responders was 41%, 38%, 31% and 12%, respectively. The median OS and PFS estimates were 24.5 months (95% CI 18.5 to not reached) and 8.2 months (95% CI 5.9 to 12.0) in patients with all-normal CRP, 16.1 months (95% CI 12.6 to 19-8) and 6.1 months (95% CI 4.9 to 7.2) in CRP-responders, 14.0 months (95% CI 8.5 to 19.4) and 5.7 months (95% CI 4.1 to 8.5) in CRP flare-responders and 8.1 months (95% CI 5.8 to 9.9) and 2.3 months (95% CI 2.2 to 2.8) in CRP non-responders (log-rank p for PFS and OS
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