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C-reactive protein flare predicts response to anti-PD-(L)1 immune checkpoint blockade in metastatic urothelial carcinoma.

European journal of cancer (Oxford, England : 1990)

Authors: Niklas Klümper, Danijel Sikic, Jonas Saal, Thomas Büttner, Franziska Goldschmidt, Jonas Jarczyk, Philippe Becker, Philip Zeuschner, Maximilian Weinke, Charis Kalogirou, Johannes Breyer, Maximilian Burger, Philipp Nuhn, Karl Tully, Florian Roghmann, Christian Bolenz, Friedemann Zengerling, Ralph M Wirtz, Michael Muders, Glen Kristiansen, Tobias Bald, Jörg Ellinger, Bernd Wullich, Michael Hölzel, Arndt Hartmann, Philipp Erben, Manuel Ritter, Markus Eckstein

PURPOSE: Robust biomarkers to predict response to immune checkpoint blockade (ICB) in metastatic urothelial carcinoma (mUC) are still in demand. Recently, early C-reactive protein (CRP) kinetics and especially the novel CRP flare-response phenomenon has been associated with immunotherapy response.

METHODS: We conducted a multicentre observational study comprising 154 patients with mUC treated with ICB to evaluate the predictive value of a previously described on-treatment CRP kinetics: CRP flare responders (at least doubling of baseline CRP within the first month after initiation of ICB followed by a decline below baseline within three months), CRP responders (decline in baseline CRP by ≥ 30% within three months without a prior flare) and the remaining patients as CRP non-responders. CRP kinetics groups were correlated with baseline parameters, PD-L1 status, progression-free survival (PFS) and overall survival (OS).

RESULTS: Objective response was observed in 57.1% of CRP responders, 45.8% of CRP flare responders and 17.9% of CRP non-responders (P < 0.001). CRP flare response was associated with prolonged PFS and OS (P < 0.001). In multivariable Cox regression analysis, CRP flare responders showed a risk reduction of ∼70% for tumour progression and death compared to CRP non-responders. Subgroup analysis of CRP flare responders revealed that patients with a long-flare response (completed flare-response kinetics ≥6 weeks on-treatment) showed even more favourable outcomes following ICB (HR = 0.18, 95%-CI: 0.07-0.48, P < 0.001).

CONCLUSION: CRP (flare)response robustly predicts immunotherapy response and outcomes in mUC independent of PD-L1 status. Thus, early on-treatment CRP kinetics is a promising low-cost and easy-to-implement biomarker to optimise therapy monitoring in patients with mUC treated with ICB.

Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

PMID: 35366569

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