High tumor mutational burden of PDAC predicts effectiveness of immune checkpoint inhibitor therapy

Patients with pancreatic ductal adenocarcinoma (PDAC) generally have a poor response to immune checkpoint inhibitor (ICI) therapy. A retrospective study among real-world PDAC patients undergoing comprehensive genomic profiling found that 1.3% of patients had high tumor mutational burden (TMB; ≥ 10 mut/Mb). Compared with low-TMB patients the high-TMB patients had better outcomes with ICIs but not with other therapies. High-TMB patients had increased mutations in BRCA2, BRAF, PALB2, and mismatch repair pathway genes, and fewer mutations in KRAS (visual abstract).