High baseline inflammatory state linked to worse outcomes in advanced non-clear cell RCC
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Key takeaways:
- High baseline inflammatory state was linked to worse outcomes in metastatic non-clear cell RCC.
- Lower baseline VEGF-A levels and higher increase in VEGF-A levels on treatment were tied to improved survival.
CHICAGO — In patients with metastatic non-clear cell renal cell carcinoma, a high systemic inflammatory state at baseline was associated with worse outcomes after treatment with atezolizumab and bevacizumab, according to a poster presented at ASCO Annual Meeting.
However, lower baseline levels of vascular endothelial growth factor A, or VEGF-A, and higher increase in VEGF-A levels on treatment were associated with improved survival. Researchers collected blood samples prior to therapy and on-treatment from 60 patients with paired tumor samples from 38 patients following two cycles of therapy. They used a fluorescent bead array platform to quantify levels of plasma soluble factors.
"This work provides a foundation both for further study of nccRCC and also for the integration of both circulating and intratumoral factors in predicting therapeutic response with immune checkpoint inhibition. It gives us a better idea of what might be mediating outcomes in nccRCC," said Renee Maria Saliby, MD, a postdoctoral research fellow at Dana-Farber Cancer Institute. "It would be important to validate these findings in independent cohorts. In addition, even though they are studied under the umbrella of nccRCC, it is crucial to obtain larger numbers of patients with each of the nccRCCs as they differ drastically."
Baseline circulating inflammatory cytokines MIP-1b, IL-1, IL-6, MCP-1 and IL-13 correlated with one another and formed an “inflammatory module,” which increased in IMDC-poor risk patients and was associated with worse PFS (P = .028). A larger increase in on-treatment levels of circulating VEGF-A was associated with clinical benefit.
An on-treatment decrease in circulating PD-L1+ T cells was associated with improved outcomes, including reductions in CD4+ PD-L1+ (HR = 0.62 [0.49-0.91], P = .016) and CD8+ PD-L1+ T cells (HR = 0.59 [0.39-0.87], P = .009) correlated with improved PFS.
"We were relatively surprised to see that a higher level of circulating VEGF-A was associated with worse outcomes to atezolizumab + bevacizumab but this result has been reported in other tumor types. We also must keep in mind that the circulating levels of VEGF-A may not fully represent the intratumor levels of VEGF-A," said Saliby. "Otherwise, a higher level of inflammation being associated with worse outcomes was expected. Also, the PD-1+ and either TIM-3+ or LAG-3+ marker for CD8+ T cells has already been validated in clear-cell RCC. This is the first study to look at it in nccRCC."
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Saliby RM, et al. Poster 4535. Presented at: ASCO Annual Meeting; June 2-6, 2022; Chicago.
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