Dramatic Response to Pembrolizumab Monotherapy in a Patient With ARID1A-Mutant Lung Adenocarcinoma: Case Report

Immunotherapy based on immune checkpoint inhibitors (ICIs) either alone or in combination with platinum-based chemotherapy has dramatically changed the therapeutic scenario in non-small cell lung cancer. However, only a subset of patients derives clinical benefits. Although programmed death-ligand 1 (PD-L1) and tumor mutational burden (TMB) are known to be prognostic and demonstrated utility in selecting patients for immunotherapy response, they are imperfect biomarkers. Recent evidence demonstrates that AT-rich interaction domain 1A (ARID1A) deficiency is associated with high antitumor immunity, mismatch repair and TMB, and thus may potentially contribute as a predictive biomarker for ICIs. We herein describe a 60-year-old woman, former smoker, who was diagnosed with lung adenocarcinoma metastatic to the left adrenal gland, with a PD-L1 expression of 60%. Next-generation sequencing test revealed an ARID1A mutation (F2141fs*59, variant allele frequency = 22.5%), TMB of 92 mut/Mb and stable microsatellite status. Given the high PD-L1 expression, elevated TMB, and ARID1A mutation, the patient started on first-line treatment with pembrolizumab monotherapy, and, 5 months after initiating treatment, presented an expressive reduction of lung lesion and a complete response of the adrenal gland. This case illustrates a dramatic response to ICI monotherapy in a lung cancer patient with ARID1A mutation. Predictive biomarkers for immune checkpoint blockade are of the utmost importance to select the patients who truly benefit from immunotherapy. The combination of biomarkers may be the most effective strategy to improve outcomes with ICIs, and ARID1A status should definitely be taken into account when present.