Several cancer types harbor alterations in the gene encoding AT-Rich Interactive Domain-containing protein 1A (ARID1A), but there are no approved therapies to address these alterations. Recent studies have shown that deficiency compromises mismatch repair proteins. Herein, we analyzed 3403 patients who had tumor tissue next-generation sequencing.

Among nine cancer subtypes with >5% prevalence of alterations, microsatellite instability-high as well as high tumor mutational burden was significantly more frequent in -altered versus wild-type tumors (20% vs 0.9%, p<0.001; and 26% vs 8.4%, p<0.001, respectively). Median progression-free survival (PFS) after checkpoint blockade immunotherapy was significantly longer in the patients with -altered tumors (n=46) than in those with wild-type tumors (n=329) (11 months vs 4 months, p=0.006). Also, multivariate analysis showed that alterations predicted longer PFS after checkpoint blockade (HR (95% CI), 0.61 (0.39 to 0.94), p=0.02) and this result was independent of microsatellite instability or mutational burden; median overall survival time was also longer in altered versus wild-type tumors (31 months vs 20 months), but did not reach statistical significance (p=0.13).

Our findings suggest that alterations merit further exploration as a novel biomarker correlating with better outcomes after checkpoint blockade immunotherapy.