Novel Risk Scoring System for Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

Abstract

Background The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria are the gold standard for risk‐stratifying patients with metastatic renal cell cancer (mRCC). We developed a novel risk scoring system for patients with mRCC treated with immune checkpoint inhibitors (ICIs). Methods We performed a retrospective analysis of 100 ICI‐treated patients with mRCC at Winship Cancer Institute from 2015 to 2018. Several baseline variables were collected, including markers of inflammation, body mass index (BMI), and sites of metastatic disease, and all were considered for inclusion in our risk scoring system. Upon variable selection in multivariable model, monocyte‐to‐lymphocyte ratio (MLR), BMI, and number and sites of metastases at baseline were used for risk score calculation. Patients were categorized using four‐level risk groups as good (risk score = 0), intermediate (risk score = 1), poor (risk score = 2), or very poor (risk score = 3–4). Cox's proportional hazard model and the Kaplan‐Meier method were implemented for survival outcomes. Results Most patients were male (66%) with clear cell renal cell carcinoma (72%). The majority (71%) received anti–programmed cell death protein‐1 monotherapy. Our risk scoring criteria had higher Uno's concordance statistics than IMDC in predicting overall survival (OS; 0.71 vs. 0.57) and progression‐free survival (0.61 vs. 0.58). Setting good risk (MLR <0.93, BMI ≥24, and D_Met = 0) as the reference, the OS hazard ratios were 29.5 (95% confidence interval [CI], 3.64–238.9), 6.58 (95% CI, 0.84–51.68), and 3.75 (95% CI, 0.49–28.57) for very poor, poor, and intermediate risk groups, respectively. Conclusion Risk scoring using MLR, BMI, and number and sites of metastases may be an effective way to predict survival in patients with mRCC receiving ICI. These results should be validated in a larger, prospective study. Implications for Practice A risk scoring system was created for patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. The results of this study have significant implications for practicing oncologists in the community and academic setting. Importantly, these results identify readily available risk factors that can be used clinically to risk‐stratify patients with metastatic renal cell carcinoma who are treated with immune checkpoint inhibitors.

Impact of BMI on Survival Outcomes of Immunotherapy in Solid Tumors: A Systematic Review

“…Overall, three studies reported data on BMI among RCC patients receiving ICIs, and were all consistent in showing a positive association of BMI with survival outcomes [ 29 , 30 , 31 ]. The study by De Giorgi et al evaluated patients treated with nivolumab in the Italian Expanded Access Program (EAP) ( n = 313) [ 29 ].…”

“…The remaining 26 studies were subsequently reviewed and screened according to our inclusion and exclusion criteria. Finally, 18 studies were included in our systematic review ( Figure 2 ) [ 18 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. The included studies were published between 2018 and 2020, and were retrospective studies, either single or multicenter; one study was a pooled analysis of patients treated with immunotherapy in the context of phase 2 and 3 trials.…”

Eosinophil prognostic scores for patients with head and neck squamous cell carcinoma treated with nivolumab

“…In non–small cell lung cancer (NSCLC) patients treated with anti‐PD‐1/PD‐L1 antibodies, the ESPILoN score, which combines smoking history, liver metastasis, lactate dehydrogenase (LDH), and the NLR, was significantly correlated with PFS and OS 11 . In recurrent/metastatic renal cell carcinoma treated with anti‐PD‐1 antibodies, due to the Emory risk scoring system, which includes the monocyte‐to‐lymphocyte ratio (MLR), body mass index (BMI), and number of metastatic sites, patients in the very poor risk group had a significantly worse PFS and OS 12 . The Gustave Roussy Immune Score (GRIm‐Score) uses LDH, serum albumin, and the NLR and is reported to be significantly correlated with OS in patients who are administered anti‐PD‐1/PD‐L1 antibodies for NSCLC 13 .…”

“…BMI), and number of metastatic sites, patients in the very poor risk group had a significantly worse PFS and OS 12. The Gustave Roussy Immune Score (GRIm-Score) uses LDH, serum albumin, and the NLR and is reported to be significantly correlated with OS in patients who are administered anti-PD-1/PD-L1 antibodies for NSCLC 13.…”

Predictive Biomarkers of Response to Immunotherapy in Metastatic Renal Cell Cancer

“…The development of biomarkers endowed with high sensitivity, specificity and accuracy able to identify which patients may truly benefit from the treatment with ICIs would allow to refine the therapeutic selection and to better tailor the treatment strategy. Furthermore, recent studies provided evidence that maybe even the prognostic stratification of mRCC patients should be refined in those treated with ICI, including the role of systemic inflammation besides the canonical criteria ( 74 ).…”