Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab

• Published in: Journal for immunotherapy of cancer 2021-02, Vol.9 (2), p.e001564
• Main Authors: Fukuda, Shohei, Saito, Kazutaka, Yasuda, Yosuke, Kijima, Toshiki, Yoshida, Soichiro, Yokoyama, Minato, Ishioka, Junichiro, Matsuoka, Yoh, Kageyama, Yukio, Fujii, Yasuhisa
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers; Biomarkers, Tumor - metabolism; C-Reactive Protein - metabolism; Cancer; Carcinoma, Renal Cell - blood; Carcinoma, Renal Cell - drug therapy; Consortia; Cytokines; Dehydrogenases; Female; Histology; Humans; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Immunotherapy Biomarkers; Kidney cancer; kidney neoplasms; Kidney Neoplasms - blood; Kidney Neoplasms - drug therapy; Male; Medical prognosis; Metastasis; Middle Aged; Monoclonal antibodies; Neoplasm Metastasis; Neutrophils; Nivolumab - therapeutic use; Oncology; Patients; Proteins; Retrospective Studies; Survival Analysis; Targeted cancer therapy; Treatment Outcome; Trends; tumor; Variables
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2020-001564

BackgroundThe dynamic change in C-reactive protein (CRP) levels, CRP kinetics, is a prognostic factor for metastatic renal cell carcinoma (mRCC) in the tyrosine kinase inhibitor era. We investigated the impact of early CRP kinetics on the efficacy of nivolumab in patients with mRCC.MethodsWe performed a retrospective analysis of 42 mRCC patients who were treated with nivolumab as a second-line or later therapy between 2016 and 2019. All patients had received previous TKI therapy. Patients were divided into three groups based on their early CRP kinetics: CRP levels increased to more than double compared with baseline within 1 month after initiation of nivolumab (flare) and then decreased to a lower value than baseline within 3 months (CRP flare-responders); CRP levels decreased by ≥30% within 3 months without “flare” (CRP responders); and the remaining patients (non-CRP responders). The maximum tumor shrinkage, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. The association of the early CRP kinetics and oncological outcomes was assessed.ResultsThe median follow-up period was 8 months. The median baseline CRP level was 23 mg/L. CRP flare-responders, CRP responders, and non-CRP responders included 11 (26%), 15 (36%), and 16 (38%) patients, respectively. Thirteen patients (31%) died of mRCC. The maximum changes in target lesions from baseline of CRP flare-responder, CRP-responder, and non-CRP responder groups were −38%, −13%, and 16%, on average, respectively (p