The Spectrum of Benefit from Checkpoint Blockade in Hypermutated Tumors

The FDA has approved immune checkpoint inhibitors for solid tumors of any histologic origin with more than 10 mutations per megabase of DNA. This study showed that in tumors with high mutational burden treated with an immune checkpoint inhibitor, improved overall survival was associated mainly with mutations in the POLE gene and with defective DNA mismatch repair, not overall mutational burden.

Automated summary

The study demonstrated that improved overall survival in tumors with high mutational burden treated with immune checkpoint inhibitors was mainly associated with mutations in the POLE gene and defective DNA mismatch repair, rather than overall mutational burden.