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AACR 2021: Influence of Aneuploidy on Response to Immunotherapy for Lung Cancer

By: Lauren Harrison, MS
Posted: Tuesday, April 27, 2021

Non–small cell lung cancer (NSCLC) cells that exhibit low amounts of aneuploidy seem to be associated with more favorable outcomes after treatment with immune checkpoint inhibition. These data were presented by João Victor Alessi, MD, of the Dana-Farber Cancer Institute, Boston, during the virtual edition of the American Association for Cancer Research (AACR) Annual Meeting 2021 (Abstract 26).

“Given the burgeoning number of recommended molecular tests for NSCLC, next-generation sequencing offers an opportunity for aneuploidy assessment. Incorporating aneuploidy score in molecular testing may aid treatment decisions and clinical trial design,” said Dr. Alessi in an institutional press release.

Researchers retrospectively analyzed samples from 279 patients with NSCLC who had undergone next-generation sequencing. Researchers generated an aneuploidy score for each sample, defined as the number of altered chromosome arms. All patients included in the study had undergone therapy with anti–PD-1/PD-L1 immune checkpoint inhibitors.

The median aneuploidy score in this cohort was 6, and this score was lower among patients with a partial response to therapy compared with those who had stable or progressive disease (4 vs. 7). Patients with an aneuploidy score of 2 or less had a longer median overall response rate (43.0%) than patients with aneuploidy scores higher than 2 (19.8%). Median progression-free survival (6.2 months vs. 2.9 months) and overall survival (19.8 months vs. 13.8 months) were also significantly longer in patients with low aneuploidy scores.

A smaller group of the samples (n = 179) had been profiled by multiplex immunofluorescence. Within this subgroup, samples with an aneuploidy score of 2 or less had higher numbers of CD8-positive, FOXP3-positive, PD-1-positive immune cells, and PD-1-positive CD8+ T cells within the tumors and in the tumor-stroma interface. PD-L1 expression levels and tumor mutation burden did not appear to change significantly with aneuploidy score.

Disclosure: For a full list of authors’ disclosures, visit abstractsonline.com.



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