Predictive impact of an early change in serum C-reactive protein levels in nivolumab therapy for metastatic renal cell carcinoma

Objective: To investigate the predictive impact of a change in serum C-reactive protein (CRP) levels during the early phase of nivolumab therapy for metastatic renal cell carcinoma (mRCC).

Patients and methods: Seventy mRCC patients treated with nivolumab after molecular-targeted therapy failure were retrospectively evaluated. Based on the CRP change, patients were classified as (1) normal: if pretreatment levels were <1 mg/dl; (2) normalized: if pretreatment levels were ≥1.0 mg/dl and nadir levels within the initial three months of nivolumab therapy declined to <1.0 mg/dl; and (3) non-normalized: if pretreatment levels were ≥1 mg/dl and nadir levels remained ≥1.0 mg/dl. The predictive association between the CRP change and progression-free survival (PFS) and overall survival (OS) after nivolumab initiation was evaluated.

Results: The PFS was significantly lower in the non-normalized group (n = 25, 35.7%) than in the normal (n = 29, 41.4%) (median: 2.33 vs. 6.28 months, P = 0.0009) and normalized (n = 16, 22.9%) (2.33 vs. 8.38 months, P = 0.0006) groups, while no differences were observed between normal and normalized groups (P = 0.610). The OS was significantly lower in the non-normalized group than in the normal (8.02 months vs. not reached, P < 0.0001) and normalized groups (8.02 vs. 26.0 months, P = 0.0047); further, the OS of the normalized group was lower than that of the normal group (P = 0.0454). Multivariate analyses showed that the CRP change was an independent factor for PFS (P = 0.0025) and OS (P = 0.0009).

Conclusions: The CRP change during the early phase of nivolumab therapy was significantly associated with mRCC patient survival and may thus be used for outcome prediction.