High BMI Levels Associated With Improved Overall Survival for Patients with mRCC Treated with ICIs

March 29, 2021
Matthew Fowler

Data from JAMA Oncology concluded that patients with a high BMI treated with PD-1/PD-L1–based immune checkpoint inhibitors for mRCC have higher overall survival rates than those with a low BMI.

Research published in JAMA Oncology found that an elevated body mass index (BMI) was associated with improved overall survival (OS) in patients treated with PD-1/PD-L1–based immune checkpoint inhibitors (ICIs) for metastatic renal cell carcinoma (mRCC).

“We investigated this obesity paradox in patients with mRCC who were treated with programmed cell death 1 protein/programmed cell death 1 ligand 1 (PD-1/ PD-L1)–based ICIs and explored potential genomic alterations according to BMI status,” wrote the investigators.

A total of 735 patients with mRCC with a BMI recorded from the International Metastatic RCC Database Consortium (IMDC) were treated with PD-1/PD-L1–based ICI in this study. Specifically, 229 patients received first-line ICI, and 230 patients received a type of combination ICI, including 142 patients with VEGF inhibitor therapy and 88 patients with CTLA-4 inhibitors.

Breaking down the patient cohort by BMI indication, 274 patients were considered to have a low BMI while 461 patients had a high BMI at ICI initiation. The median follow-up was 13.5 months (range, <1 to 78.6 months).

The cohort of patients with a high BMI saw a significantly improved 1-year OS rate at 79% compared with the cohort of patients with a low BMI at 66% (adjusted HR, 0.75; 95% CI, 0.57-0.97; P = .03). When analyzing these patients by different subgroups including sex, IMDC group, histology, and type/line of therapy, the association with BMI was consistent.

More, the cohort of patients with a high BMI had a higher overall response rate (ORR) of 30% versus 21% for those with a low BMI; time to treatment failure (TTF) was also better in those with a high BMI, at a median of 7.4 months (95% CI, 6.7-9.0) versus 4.9 months (95% CI, 3.8-6.9).

Importantly, these data were not statistically significant in multivariable models (ORR: adjusted OR, 1.51; 95% CI, 0.98-2.32; P = .06; TTF: adjusted HR, 0.98; 95% CI, 0.80-1.20; P = .83).

“These findings are consistent with the obesity paradox that was previously seen during the VEGF-targeted therapy era,” wrote the investigators. “Several hypotheses have attempted to explain this clinical observation in RCC.”

Finally, for the 319 patients who had available next-generation sequencing data, both genomic alteration frequencies and tumor mutational burden were found to be similar between patients with both high and low BMI.

Low BMI was defined as less than 25, while high BMI was defined as 25 or more. The association for patients with BMI levels was assessed by a multivariable logistic regression model, with a focus on OS, TTF, and ORR.

The main limitation of these data are the presence of potential biases due to the retrospective nature of the research, as well as the lack of robust gene-expression profiling. Moreover, radiological measurements are available to study outcomes that may be more sophisticated than BMI, although those options are much more cumbersome to examine.

“Ultimately, further correlative work is required to explore the biological underpinnings for similar findings across other solid tumors that are treated with ICIs,” wrote the investigators.

Reference:

Lalani AKA, Bakouny Z, Farah S, et al. Assessment of Immune Checkpoint Inhibitors and Genomic Alterations by Body Mass Index in Advanced Renal Cell Carcinoma. JAMA Oncology. Published online March 4, 2021. doi: 10.1001/jamaoncol.2021.0019