142P - The predictive biomarker for immune-related adverse events (irAEs) in patients with metastatic renal cell carcinoma treated with the combination therapy of nivolumab plus ipilimumab: Musashino study-irAE

Background

Combination immunotherapy with an anti-PD-1 inhibitor and an anti-CTLA-4 inhibitor is used as first-line therapy in metastatic renal cell carcinoma (mRCC). While providing the benefit of a certain population of long-term responders, the frequency of immune-related adverse events (irAEs) is known to be high with the combination therapy. Thus, predictive biomarkers of irAEs could help guide treatment strategies.

Methods

We performed a retrospective review of patients with mRCC treated with nivolumab plus ipilimumab from multiple centers between September 2018 and February 2021. We investigated clinical and laboratory findings, including age, sex, absolute eosinophil count, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and C-reactive protein (CRP) level at the baseline, for their association with the occurrence of irAEs using multivariate analyses. In addition, we evaluated the relationship between the occurrence of irAEs and the fold change of CRP and absolute eosinophil count from the baseline to 3 weeks after the initiation of ICIs.

Results

A total of 131 patients were included. The median age was 67 years (range 28-87 years), and 92 patients were male (70.2%). Any grade of irAEs occurred in 95 (72.5%) patients, and grade 3 or more irAEs occurred in 59 (45.0%) patients. Among the clinical and blood markers at the baseline, lower CRP level was significantly associated with higher occurrence of any grade and grade 3 or more irAEs in multivariate analyses (p=0.0004 and p=0.0122, respectively). While the fold change of both CRP and absolute eosinophil count from the baseline to 3 weeks after the initiation of ICIs were not related to the occurrence of irAEs (p=0.2968 and p=0.5599, respectively).

Conclusions

A lower baseline CRP level was associated with a higher incidence of irAEs in patients with mRCC treated with nivolumab plus ipilimumab. The potential predictive impact of this biomarker needs to be further prospectively investigated.

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 Pharmaceutical, Bristol Myers Squibb, Eisai; Financial Interests, Institutional, Research Grant: MSD, Ono Pharmaceutical. All other authors have declared no conflicts of interest.