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• W4308376676 abstract "<h3>Background</h3> Age-associated pro-inflammatory states may result in decreased response to immune checkpoint inhibitors (ICI) in older patients (pts) with cancer. We explored the association of circulating inflammatory markers with response to ICIs, and investigate potential differences in transcriptional and TME signatures of pts ≥80-years (yr) of age and younger. <h3>Methods</h3> We built a multicenter, international database of pts with different tumors treated with ICIs monotherapy between 2011 and 2021 from 11 academic centers in the US and Europe. Retrospective analysis of 885 pts compared objective response rates (ORR; iRECIST), median progression-free survival (mPFS) and overall survival (mOS) between pts ≥80-yr and <80-yr, and stratified them across serum pre-treatment levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII=PxN/L). Optimal cut-off values for high (H) <i>vs.</i> low (L) levels were determined using receiver operating characteristic curves. DNA (592-gene panel/whole exome) and RNA (whole transcriptome) next-generation sequencing, immunohistochemistry (IHC) and TME analysis (MCP-counter) were performed on 24,123 independent samples of non-small cell lung cancer (NSCLC), melanoma (MEL) and renal cell carcinoma (RCC) submitted to a CLIA-certified laboratory (Caris Life Sciences, Phoenix, AZ). Results were compared between pts ≥80-yr and <80-yr. <h3>Results</h3> Table 1 summarizes pts baseline characteristics. Pts <80-yr had better ORR (<i>P<0.01</i>), but comparable mOS and mPFS to ≥80-yr (table 2). In pts ≥80-yr, NLR-L and SII-L were associated with higher ORR (<i>P<0.01</i> and <i>P<0.05</i>; figure 1). All pts with NLR-L, MLR-L and SII-L, had longer mOS (<i>P<0.01;</i> figure 2). All PLR-L and SII-L pts had significantly longer mPFS (<i>P<0.01</i>; figure 3). Compared to pts <80-yr, NSCLC ≥80-yr had increased abundance of fibroblasts, dendritic cells and macrophages (<i>P<0.01</i>) in their TME and lower TMB-H (<i>P<0.001</i>). MEL ≥80-yr pts had fewer TME infiltrating T-lymphocytes (<i>P=0.02</i>), a1.24-fold increased expression of <i>IL-6</i>. RCC ≥80-yr pts had 0.56-fold decreased expression of <i>GZMB</i>, and lower PD-L1 (IHC-SP142, ≥2+|5%) expression (<i>P<0.05;</i> figure 4<b>)</b>. Additional correlative biomarkers will be reported in the poster. <h3>Conclusions</h3> Lower levels of circulating inflammatory markers associated with significantly longer survival and better response rates to ICIs. SII-L and NLR-L specifically are potential biomarkers of response to ICI in pts ≥80-yr. This is the first study to evaluate the role of serum markers of inflammation as potential biomarkers of response to ICI in older pts with cancer, along with molecular correlate. Circulating inflammatory markers, and associated gene expression and TME composition suggest potential unique, cancer-specific biomarkers of response to ICIs in this population. <h3>Ethics Approval</h3> The study was approved by the institutional review board at each participating institution. Written informed consent was waived, given the retrospective nature of the study and the de-identified status of collected data." @default.
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• W4308376676 date "2022-11-01" @default.
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• W4308376676 title "112 Circulating and molecular markers of inflammation: impact on treatment response and survival among older patients with cancer treated with immune checkpoint inhibitors" @default.
• W4308376676 doi "https://doi.org/10.1136/jitc-2022-sitc2022.0112" @default.
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