Early CRP kinetics to predict long-term efficacy of first-line immune-checkpoint inhibition combination therapies in metastatic renal cell carcinoma: an updated multicentre real-world experience applying different CRP kinetics definitions

Research output: Contribution to journalResearch articleContributedpeer-review


  • Benedikt Hoeh - , University Hospital Frankfurt (Author)
  • Cristina Cano Garcia - , University Hospital Frankfurt (Author)
  • Severine Banek - , University Hospital Frankfurt (Author)
  • Niklas Klümper - , University of Bonn Medical Center (Author)
  • Alexander Cox - , University of Bonn Medical Center (Author)
  • Jörg Ellinger - , University of Bonn Medical Center (Author)
  • Philipp Schmucker - , University Hospital of Würzburg (Author)
  • Oliver Hahn - , University Hospital of Würzburg (Author)
  • Angelika Mattigk - , Ulm University Medical Center (Author)
  • Friedemann Zengerling - , Ulm University Medical Center (Author)
  • Philippe Becker - , University Hospital of Saarland (Author)
  • Kati Erdmann - , Department of Urology (Author)
  • Bjoern Thorben Buerk - , Department of Urology (Author)
  • Luka Flegar - , University of Marburg (Author)
  • Johannes Huber - , University of Marburg (Author)
  • Charis Kalogirou - , University Hospital of Würzburg (Joint last author)
  • Philip Zeuschner - , University Hospital of Saarland (Joint last author)


OBJECTIVES: Although biomarkers predicting therapy response in first-line metastatic renal carcinoma (mRCC) therapy remain to be defined, C-reactive protein (CRP) kinetics have recently been associated with immunotherapy (IO) response. Here, we aimed to assess the predictive and prognostic power of two contemporary CRP kinetics definitions in a large, real-world first-line mRCC cohort.

METHODS: Metastatic renal carcinoma patients treated with IO-based first-line therapy within 5 years were retrospectively included in this multicentre study. According to Fukuda et al., patients were defined as 'CRP flare-responder', 'CRP responder' and 'non-CRP responder'; according to Ishihara et al., patients were defined as 'normal', 'normalised' and 'non-normalised' based on their early CRP kinetics. Patient and tumor characteristics were compared, and treatment outcome was measured by overall (OS) and progression-free survival (PFS), including multivariable Cox regression analyses.

RESULTS: Out of 316 mRCC patients, 227 (72%) were assigned to CRP groups according to Fukuda. Both CRP flare- (HR [Hazard ratio]: 0.59) and CRP responders (HR: 0.52) had a longer PFS, but not OS, than non-CRP responders. According to Ishihara, 276 (87%) patients were assigned to the respective groups, and both normal and normalised patients had a significantly longer PFS and OS, compared with non-normalised group.

CONCLUSION: Different early CRP kinetics may predict therapy response in first-line mRCC therapy in a large real-world cohort. However, further research regarding the optimal timing and frequency of measurement is needed.


Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalClinical and Translational Immunology
Issue number10
Publication statusPublished - 2023

External IDs

PubMedCentral PMC10600333
Scopus 85174959307
ORCID /0000-0003-3717-3637/work/151433551