139MO - Prognostic significance of the mechanism of inflammatory markers in advanced renal cell carcinoma patients treated with nivolumab plus ipilimumab

Background

The discovery of a useful biomarker for advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitors is expected. In this study, we aimed to investigate whether the mechanism of inflammatory makers is associated with the efficacy of nivolumab plus ipilimumab.

Methods

We retrospectively analyzed data of patients with clear cell RCC (ccRCC) treated with nivolumab plus ipilimumab as a first-line therapy. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and C-reactive protein (CRP) were assessed at baseline, 3 weeks, 6 weeks, and 9 weeks after the start of the treatment. Responders were defined as patients with the best overall complete response or partial response, whereas non-responders were those with stable or progressive disease.

Results

A total of 84 ccRCC patients treated with nivolumab plus ipilimumab were retrospectively analyzed. At baseline, NLR was significantly higher in non-responders than in responders, but other factors did not significantly differ. At week 9, NLR and CRP were significantly higher in non-responders than in responders. On univariate analysis, higher NLR at baseline, week 3, and week 9 and higher CRP at weeks 6 and 9 were associated with poor overall survival (OS). On multivariate analysis, elevated CRP at week 9 was an independent risk factor for shorter OS. Elevated CRP levels (≥1.0 mg/dL) at week 9 indicated poor progression-free survival (PFS) and OS than CRP < 1.0 mg/dL (PFS: HR = 2.78, P= 0.001, OS: HR = 3.55, P= 0.002). Additionally, among the 68 patients who received at least three cycles of nivolumab plus ipilimumab, CRP ≥ 1.0 mg/dL at week 9 was also a poor prognostic factor for PFS and OS than CRP < 1.0 mg/dL (PFS: HR =2.58, P=0.005, OS: HR 2.76, P=0.028).

Conclusions

Elevated CRP levels at week 9 can indicate poor OS, PFS, and BOR in ccRCC patients receiving nivolumab plus ipilimumab. Those who did not achieve CRP ≤ 1 mg/dL at week 9 should undergo a different treatment strategy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

Y. Miura: Financial Interests, Personal, Invited Speaker: Takeda, MSD, Bristol Myers Squibb, Ono Pharmaceutical, Merck BioPharma, Eisai, Astellas Pharma; Financial Interests, Institutional, Invited Speaker: Ono Pharmaceutical, MSD. All other authors have declared no conflicts of interest.