Prognostic Significance of Inflammatory Markers in Patients with Advanced Renal Cell Carcinoma Receiving Nivolumab plus Ipilimumab

Compared to conventional drugs, nivolumab plus ipilimumab has shown robust efficacy in the treatment of advanced renal cell carcinoma (RCC). However, regarding the objective response rate, the combination treatment with nivolumab plus ipilimumab may be inferior to that of immune checkpoint inhibitors and vascular endothelial growth factor inhibitors, although no direct comparisons have yet been made. Furthermore, a high primary progressive disease (PD) rate of 20% and a high incidence of immune-related adverse events (irAEs) are problematic. Thus, it is desirable to establish biomarkers to identify patients who are less likely to benefit from this treatment.

It is well known that inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP), have long been important for predicting survival in advanced renal cell carcinoma. Therefore, we focused on these biomarkers and aimed to investigate whether they are associated with the efficacy of nivolumab plus ipilimumab therapy before and during four cycles of treatment.

In this study, we retrospectively analyzed data from patients with clear cell RCC (ccRCC) treated with nivolumab plus ipilimumab as the first-line therapy. NLR, MLR, PLR, and CRP were assessed at baseline and 3, 6, and 9 weeks after the start of treatment. A total of 84 ccRCC patients were identified, and on univariate and multivariate analyses, the NLR at week 3, CRP at week 6, and NLR and CRP at week 9 were significant risk factors for shorter overall survival (OS). Receiver operating characteristic curve analysis and Kaplan-Meier analysis showed that an NLR of ≥ 2.4 at week 3, a CRP of ≥ 1.4 mg/dL at week 6, and an NLR of ≥ 4.8 and CRP of ≥ 1.0 mg/dL at week 9 were associated with worse OS (hazard ratios [HR] = 5.70, P =0.008, HR =3.23, P =0.004, HR =7.38, P <0.001 and HR =3.55, P =0.002, respectively).

Studies on the kinetics of tumor markers have highlighted that NLR and CRP have different prognostic abilities. Based on these results, we developed a prognostic model using both NLR and CRP at week 9. This model proposed a better prognostic classification (C-index = 0.78). Using the NLR and CRP at week 9, clinicians can reconsider the treatment strategy without completing four cycles of nivolumab plus ipilimumab therapy. We believe that this finding is important because it provides a group of patients with a poor prognosis a few weeks to try new treatments.

Written by:

Takayuki Nakayama, MD, PhD, Department of Urology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
Hideki Takeshita, MD, PhD, Department of Urology, Saitama Medical Center, Saitama Medical University, Saitama, Japan

Read the Abstract

Login