Poor performance status patient with long-lasting major response to pembrolizumab in advanced non-small-cell lung cancer with coexisting POLE mutation and deficient mismatch repair pathway

Abstract

Immunotherapy with immune checkpoint inhibitors (ICIs) represents a major breakthrough in lung cancer treatment. For patients with advanced non-small-cell lung cancer (NSCLC) and poor performance status (PS), the availability of sensitivity markers to immune-checkpoint inhibitors (ICI) would be useful for attending physicians and assist them in their decision-making process. Deficient mismatch repair (dMMR) can lead to high microsatellite instability (MSI-H) and coexist with mutations in polymerase proofreading (DNA polymerase Epsilon POLE and delta 1 POLD1) with a specific mutational signature. This would result in high tumor mutational burden and programmed cell death protein ligand 1 (PD-L1) overexpression. We report herein on a NSCLC case with MSI-H and POLE mutation in a patient with inaugural poor general condition, who exhibited prolonged response to anti-programmed cell death protein (PD-1) therapy. Additionally, there was a marked improvement of the patient's performance status, from PS 3 before ICI administration to PS 1 upon ICI therapy.

Keywords: Anti-PD1; Immunotherapy; MMR; MSI-H; NSCLC; POLE.