Loss of subcutaneous fat after initiation of immune checkpoint inhibitors (ICIs) is associated with poor survival in patients with metastatic clear cell renal cell carcinoma (RCC), according to study findings presented at the 38th Annual Congress of the European Association of Urology (EAU23) and published in the International Journal of Molecular Sciences.
In the study of 60 patients treated with ICIs, those with a subcutaneous fat loss of 5% or more per month had significantly shorter overall survival (median, 9.5 months vs not reached) and progression-free survival (median, 2.6 months vs 33.5 months) compared with patients who had less than a 5% loss or a gain in subcutaneous fat.
Patients with a monthly 5% or more subcutaneous fat loss had a significant 45% and 52% increased risk of all-cause mortality and progression, respectively. The investigators observed worse survival rates across lines of treatment and IMDC risk criteria. Patients with a subcutaneous fat loss of 5% or more per month also had a significantly lower objective response rate (10.0% vs 62.5%), including during first-line therapy (28.6% vs 78.9%) and subsequent therapy (0% vs 47.6%).
Of the 60 patients, 33 received nivolumab monotherapy, 17 received nivolumab plus ipilimumab followed by nivolumab monotherapy, 7 received pembrolizumab plus axitinib, and 3 received avelumab plus axitinib. The investigators used abdominal CT scans before and after ICI therapy to calculate change in subcutaneous fat.
Based on transcriptomics of the primary tumors, patients with subcutaneous fat loss had an immune-suppressive tumor microenvironment.
“The transcriptomic characteristics, particularly immune-related features of the [tumor microenvironment], significantly differed between patients with and without [subcutaneous fat] loss, implying that it may have the potential to link loss of fat and poor clinical outcomes in these patients,” the investigators concluded.
Lee J, Lee SM, Lee JH, et al. Prognostic value of fat loss in patients with metastatic clear cell renal cell carcinoma treated with immune checkpoint inhibition. Presented at: EAU23 Congress, Milan, Italy, March 10-13. Abstract A0336.
Lee JH, Hwang S, Jee BA, et al. Fat loss in patients with metadstatic clear cell renal cell carcinoma treated with immune checkpoint inhibitors. Int J Mol Sci. 2023 Feb; 24(4): 3994. Published online February 16, 2023. doi:10.3390/ijms24043994
This article originally appeared on Renal and Urology News