In a study reported in a research letter in JAMA Oncology, Lalani et al found that higher body mass index (BMI) was associated with better overall survival among patients with metastatic renal cell carcinoma receiving anti–PD-1/PD-L1–based immune checkpoint inhibitor treatment. No association of BMI with genomic alterations or tumor mutational burden was observed.
As stated by the investigators, “An elevated BMI has been associated with an increased risk of renal cell carcinoma. Previously, higher BMI was shown to be a positive prognostic factor for patients with metastatic clear cell renal cell carcinoma who were treated during the vascular endothelial growth factor (VEGF)-targeted therapy era…. We investigated this obesity paradox in patients with metastatic renal cell carcinoma who were treated with PD-1/PD-L1–based immune checkpoint inhibitors and explored potential genomic alterations according to BMI status.”
Study Details
The study included 735 patients with metastatic renal cell carcinoma from the International Metastatic RCC Database Consortium (IMDC) database with a recorded BMI who were treated with PD-1/PD-L1–based immune checkpoint inhibitor therapy. Analysis of association of BMI with treatment outcomes was adjusted for IMDC risk classifications, age, sex, race/ethnicity, histology, sarcomatoid features, line of therapy, and type of immunotherapy. Among 319 patients with available next-generation sequencing data (OncoPanel, 275–447 genes), genomic alteration frequencies (nonsense, insertions/deletions, and missense) and tumor mutational burden were compared according to BMI status.
“[A]n elevated BMI was independently associated with improved overall survival in patients with metastatic renal cell carcinoma who were treated with PD-1/PD-L1–based immune checkpoint inhibitors. These findings are consistent with the obesity paradox that was previously seen during the VEGF-targeted therapy era.”— Lalani et al
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Key Findings
Among the 735 patients, 274 patients (37%) had a BMI < 25 kg/m2 (low BMI) and 461 (63%) had a BMI ≥ 25 kg/m2 (high BMI) at immune checkpoint inhibitor initiation. Overall, 229 patients (31%) received first-line immune checkpoint inhibitors and 230 (31%) received combination therapy, including 142 (19%) with anti-VEGF and 88 (12%) with anti–CTLA-4/other therapies.
Median follow-up was 13.5 months (range = < 1–78.6 months). Overall survival at 1 year was 79% in the high BMI group vs 66% in the low BMI group (adjusted hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.57–0.97, P = .03). The association was consistent in subgroups according to sex, IMDC group, histology, and type/line of therapy.
The high BMI group exhibited numerically improved objective response rate (30% vs 21%; adjusted odds ratio = 1.51, 95% CI = 0.98–2.32, P = .06) and time to treatment failure (median = 7.4 vs 4.9 months, adjusted HR = 0.98, 95% CI = 0.80–1.20, P = .83).
Among 319 patients with available next-generation sequencing data, no difference in genomic alteration frequencies (all q > 0.50) or tumor mutational burden (6.8 vs 6.8 mutations per megabase, P = .90) was found according to high vs low BMI.
The investigators concluded, “In this multinational analysis from the IMDC, an elevated BMI was independently associated with improved overall survival in patients with metastatic renal cell carcinoma who were treated with PD-1/PD-L1–based immune checkpoint inhibitors. These findings are consistent with the obesity paradox that was previously seen during the VEGF-targeted therapy era.”
Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by National Cancer Institute SPORE grants, as well as the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at Dana-Farber Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
