Loss of subcutaneous fat after initiation of immune checkpoint inhibitors (ICI) 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) in Milan, Italy, and concurrently 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 vs 33.5 months) compared with those with 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, Jihwan Lee, MD, of Samsung Medical Center in Seoul, South Korea, reported on behalf of his colleagues. They 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 (28.6% vs 78.9%) and subsequent therapy (0% vs 47.6%).
Of the 60 patients, 33 received nivolumab monotherapy, 17 nivolumab plus ipilimumab followed by nivolumab monotherapy, 7 pembrolizumab plus axitinib, and 3 avelumab plus axitinib. The investigators used abdominal computed tomography 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, Dr Lee’s team noted in their journal article.
“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