Relationship Between Pretreatment Body Composition and Clinical Outcomes in Patients With Metastatic Renal Cell Carcinoma Receiving First-Line Ipilimumab Plus Nivolumab - Beyond the Abstract
There remains limited data regarding the relationship between BC variables and outcomes in patients with mRCC treated with specific front-line immune checkpoint inhibitor (ICI) regimens or classes, such as the dual ICI combination of ipilimumab + nivolumab. Therefore, the goal of our study was to examine potential associations between clinical outcomes and BC variables on CT in patients with mRCC receiving ipilimumab + nivolumab as first-line systemic therapy.
To do this, we retrospectively reviewed all patients with mRCC treated with first-line ipilimumab + nivolumab at one institution before June 1, 2021, with an analyzable baseline CT scan. CT images were segmented at the level of the third lumbar vertebrae and previously validated software was used to measure the areas of skeletal muscle (SM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT). These areas were converted to indices by dividing the component area by squared patient height (m2) (SMI, SATI, VATI, respectively) to allow cross-patient comparison. BC variables were dichotomized as high or low using sex-specific cutoffs. We then examined relationships between BC variables (including BMI) and clinical outcomes, including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
Ninety-nine patients met the study criteria and were analyzed. Controlling for age, IMDC risk, and sex (for BMI analyses), high vs. low SMI (HR=2.433, CI: 1.397-4.238, P =.0017), high vs. low SATI (HR=1.641, CI: 1.023-2.632, P =.0398), and obese BMI (≥ 30 kg/m 2 ) vs. normal/overweight BMI (<30 kg/m 2 ) (HR=1.859, CI: 1.156-2.989, P =.0105) were significantly associated with PFS. Median OS for low SMI patients was higher (42.74 months, CI: 26.84, NR) than median OS for high SMI patients (27.01 months, CI: 15.28, NR) (adjusted HR=1.728, CI: 0.909-3.285, P =.0952). No BC variables were significantly associated with OS or objective response rate.
In this large cohort comprised entirely of systemic-therapy-naïve patients with mRCC, we found that low SMI and low SATI were associated with significantly improved PFS. The median OS for patients with low SMI was numerically higher than the median OS for patients with high SMI, although this was not statistically significant and OS assessment was limited by duration of follow up and the number of OS events.
These results contribute to a growing body of literature demonstrating the utility of BC variables as prognostic biomarkers for patients with RCC receiving immunotherapy. Our study is the first study, to our knowledge, to study BC in a cohort of patients receiving the same treatment regimen and in the treatment naïve setting, which is of importance given the potentially different roles BC may play in different treatment or disease settings. The findings of improved response duration for patients with low SMI and patients with low SATI were unique compared to prior studies of BC in patients with mRCC and potentially highlight the different roles of BC in patients that are treatment naïve and receiving a purely immunotherapy-based regimen.
Future validation in a larger multi-institution cohort is needed. Translational work to help understand the mechanism through which low SMI and low SATI are associated with improved outcomes is also of importance. Ultimately these findings, if validated in additional cohorts, could help inform future interventional studies, such as dietary or exercise interventions, to modify these factors and hopefully improve outcomes for patients with mRCC.
Written by: Hannah Dzimitrowicz McManus, MD, Hematology Oncology Fellow, Duke University Medical Center, Durham, NC
Read the Abstract