Comorbidity Burden and Effectiveness of Immunotherapy in Metastatic Renal Cell Carcinoma

Comorbid conditions complicate the care of patients with cancer and frequently cause exclusion of patients from clinical trials.

Data from patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitor (ICI)-based combinations in the first line setting were collected. The comorbidity burden was assessed at baseline by using the age-adjusted Charlson Comorbidity Index (CCI). Patients were stratified into 2 groups to predict overall survival (OS) through maximally selected rank statistics. The primary outcomes were time to treatment failure (TTF) and OS. The secondary outcome was the rate of adverse events (AEs) leading to dose reduction or treatment discontinuation.

A total of 304 patients were included. Most patients were male (73%), had clear cell RCC (91.4%), and were treated with nivolumab + ipilimumab (53.6%). The most common comorbidities were diabetes (18.4%), followed by previous myocardial infarction (12.8%), chronic kidney disease (6.6%), and chronic pulmonary disease (5.6%). After adjusting for baseline prognostic factors in mRCC including the International mRCC Database Consortium (IMDC) risk, TTF (Hazard Ratio [HR], 1.51, 95% Confidence Interval [CI], 1.09-2.10, P= .013) and OS (HR: 1.98, 95% CI, 1.33-2.94, P= .001) were worse in the CCI-high group vs. the CCI-low group. The rates of AEs leading to dose reduction or treatment discontinuation were comparable between the 2 groups.

Despite similar rates of AEs leading to dose reduction or treatment discontinuation, a high comorbidity burden is associated with worse outcomes in patients with mRCC treated with first-line ICI-based therapies. Our study underscores the necessity for a multidimensional approach to assess the comorbidity burden in patients with mRCC receiving ICI-based combinations.