C‐reactive protein flare‐response predicts long‐term efficacy to first‐line anti‐PD‐1‐based combination therapy in metastatic renal cell carcinoma. Issue 12 (6th December 2021)

• Record Type: Journal Article
• Authors: Klümper, Niklas; Schmucker, Philipp; Hahn, Oliver; Höh, Benedikt; Mattigk, Angelika; Banek, Severine; Ellinger, Jörg; Heinzelbecker, Julia; Sikic, Danijel; Eckstein, Markus; Strauß, Arne; Zengerling, Friedemann; Hölzel, Michael; Zeuschner, Philip; Kalogirou, Charis
• Is Part Of: Clinical & translational immunology. Volume 10:Issue 12(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-06
• Subjects: biomarker -- checkpoint inhibition -- C‐reactive protein -- CRP flare‐response -- immunotherapy -- metastatic renal cell carcinoma; Immunologic diseases -- Periodicals; Immunology -- Periodicals; Clinical medicine -- Periodicals; Immune System Diseases -- therapy; Immunotherapy; Immunologic Factors -- therapeutic use; Translational Medical Research; Molecular Targeted Therapy; Clinical medicine; Immunologic diseases; Immunology; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 616.079
• DOI: 10.1002/cti2.1358
• Languages: English
• ISSNs: 2050-0068

Abstract

Abstract: Objectives: Immune checkpoint blockade (IO) has revolutionised the treatment of metastatic renal cell carcinoma (mRCC). Early C‐reactive protein (CRP) kinetics, especially the recently introduced CRP flare‐response phenomenon, has shown promising results to predict IO efficacy in mRCC, but has only been studied in second line or later. Here, we aimed to validate the predictive value of early CRP kinetics for 1st‐line treatment of mRCC with αPD‐1 plus either αCTLA‐4 (IO+IO) or tyrosine kinase inhibitor (IO+TKI). Methods: In this multicentre retrospective study, we investigated the predictive potential of early CRP kinetics during 1st‐line IO therapy. Ninety‐five patients with mRCC from six tertiary referral centres with either IO+IO ( N = 59) or IO+TKI ( N = 36) were included. Patients were classified as CRP flare‐responders, CRP responders or non‐CRP responders as previously described, and their oncological outcome was compared. Results: Our data validate the predictive potential of early CRP kinetics in 1st‐line immunotherapy in mRCC. CRP responders, especially CRP flare‐responders, had significantly prolonged progression‐free survival (PFS) compared with non‐CRP responders (median PFS: CRP flare‐responder: 19.2 months vs. responders: 16.2 vs. non‐CRP responders: 5.6, P < 0.001). In both the IO+IO and IO+TKI subgroups, early CRP kinetics remained significantly associated with improved PFS. CRP flare‐response was also associated with long‐term response ≥ 12 months. Conclusions: Early CRP kinetics appears to be a low‐cost and easy‐to‐implement on‐treatment biomarker to predict response to 1st‐line IO combination therapy. It has potential to optimise therapy monitoring and might represent a new standard of care biomarker for immunotherapy in mRCC. Abstract : In this multicentre study, we investigated the predictive potential of early serum C‐reactive protein (CRP) kinetics during 1st‐line immunotherapy in metastatic renal cell carcinoma (mRCC). Out of 95 patients with mRCC, those with significant CRP flare‐response or decrease in CRP levels had superior outcomes. This potential biomarker could improve therapy monitoring of mRCC and eventually also treatment stratification.