Germline DNA damage response gene mutations as predictive biomarkers of immune checkpoint inhibitor efficacy.

ABSTRACT:

Background

Impaired DNA damage response (DDR) can affect immune checkpoint inhibitors (ICI) efficacy and lead to heightened immune activation. We assessed the impact of pathogenic or likely pathogenic (P/LP) germline DDR mutations on ICI response and toxicity.

Materials and methods

A retrospective analysis of 131 cancer patients with germline DNA testing and ICI treatment was performed.

Results

Ninety-two patients were DDR-negative (DDR-), and 39 had ≥1 DDR mutation (DDR+). DDR+ patients showed higher objective response rates (ORRs) compared to DDR- in univariate and multivariable analyses, adjusting for age and metastatic disease (62% vs. 23%, unadjusted OR = 5.41; 95% CI, 2.41-12.14; adjusted OR 5.94; 95% CI, 2.35-15.06). Similar results were seen in mismatch repair

SUBMITTER: Dennis MJ 

PROVIDER: S-EPMC10859432 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature