medwireNews: Low levels of aneuploidy may be associated with a distinct tumor immune microenvironment and an improved response to immune checkpoint inhibitors (ICIs) in people with non-small-cell lung cancer (NSCLC), US research suggests.
The findings, presented at the virtual AACR Annual Meeting 2021, were based on a next-generation sequencing analysis of tumors from 299 patients with NSCLC who had been treated with ICIs.
Joao Alessi, from Dana-Farber Cancer Institute in Boston, Massachusetts, USA, reported that the median tumor aneuploidy score (AS), defined as the total number of altered chromosome arms, among the retrospective cohort was significantly lower for individuals with a partial response to ICI therapy than for those with stable or progressive disease, at a median of 4 versus 7.
The researchers then calculated that an AS cutoff of 2 was the best discriminator of response.
Specifically, participants with an AS of 2 or lower (n=79) had a significantly higher overall response rate to ICIs than those with a score above 2, at 43.0% versus 19.1%.
People with an AS at or below the cutoff also had significantly longer median progression free survival (6.2 vs 3.2 months) and overall survival (21.0 versus 13.8 months) when treated with ICIs relative to people with a higher AS.
And after adjusting for potential confounders such as performance status, presence of oncogenic driver mutations, PD-L1 expression, tumor mutational burden, and line of treatment, the researchers found that an AS of 2 or lower was associated with a significant 29% reduced risk for disease progression and a nonsignificant 25% reduced risk for death compared with a higher AS.
By comparison, the team found that there was no significant association between AS and response in a cohort of 85 patients who received platinum-doublet chemotherapy.
Alessi also reported that NSCLCs with an AS of 2 or lower had significantly higher numbers of CD8+, FOXP3+, PD-1+ immune cells, and PD-1+ CD8+ T cells, than those with a higher AS, both intratumorally and when considering total cell numbers within the tumor and the tumor–stroma interface.
The presenter concluded that the study “provided an improved understanding of aneuploidy as a surrogate of response to immunotherapy.”
He added: “Given the growing number of recommended molecular tests for NSCLC, next-generation sequencing offers an opportunity for aneuploidy assessment.”
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