Published recently in JAMA Oncology, retrospective data indicates that better survival outcomes are found in metastatic renal cell carcinoma (mRCC) patients with a high body mass index (BMI) who are treated with anti-PD-1/PD-L1 immune checkpoint inhibitors (ICIs). Propelling the obesity paradox further, these results support similar previous observations in cancer patients treated with anti-CTLA-4 and anti-VEG-F immunotherapies. Identifying 735 mRCC patients treated with anti-PD-1/PD-L1 ICIs from the International Metastatic RCC Database Consortium, the study assessed overall survival (OS), overall response rate (ORR) and time to treatment failure (TTF), based on BMI.
274 patients in the study cohort had a low BMI (BMI <25), whilst 461 had a high BMI (>_25). Importantly, patients were exposed to different ICI combinations and at different stages, with 229 patients receiving PD-1/PD-L1-based ICI therapy in the first line and 230 patients receiving ICI combination therapy, including 142 patients having received VEGF inhibitor therapy and a further 88 patients receiving CTLA-4 inhibitors. At a medium follow-up of 13.5 months, patients with a high BMI had a significantly longer OS than low BMI patients (79% vs. 66%; HR[95%CI]: 0.75[0.57-0.97], P= 0.03). Furthermore, this significant difference was observed even when patients were assessed by sex, IMBC group, histology and type/line of therapy.
Patients with a high BMI also had a better ORR, compared to low BMI patients, at 30% and 21%. Similar observations were made when assessing TTF, with high BMI patients having a median TTF of 7.4 months, compared to 4.9 months in low BMI patients. However, it should be noted that these data was not significant in multivariate models (ORR: OR[95%CI]: 1.51[0.98-2.32], P= 0.06. TTF: HR[95%CI]: 0.98[0.80-1.20], P= 0.83). Additionally, 319 patients had next-generation sequencing data available. Comparing this data between high and low BMI patients, comparable frequencies of genomic alterations and tumour mutational burdens were observed.
This data offers valuable insight into how BMI affects ICI response. However, this data was not prospective and lacked next-generation sequencing data for the entire cohort, which may affect survival outcomes in the remaining patients whose tumour mutational burden cannot be determined. Ultimately, further correlative research is needed to validate these results.
Lalani A-K et al., Assessment of Immune Checkpoint Inhibitors and Genomic Alterations by Body Mass Index in Advanced Renal Cell Carcinoma. JAMA Oncology. 2021. [epub].