What happened, in summary

A 72-year-old man came to the hospital on September 14, 2021, with a cough that had worsened over 1 month. Examination was unremarkable, but laboratory testing showed a markedly elevated platelet count and increased tumor markers, including alpha-fetoprotein and cytokeratin. Chest CT showed multiple nodules in both lungs, a mass in the left upper lobe, and enlarged mediastinal and right hilar lymph nodes. CT-guided biopsy of the left lung mass confirmed poorly differentiated adenocarcinoma. Immunohistochemistry showed CK7-positive, TTF-1-positive disease with Ki-67 around 60%; ALK was negative, BRAF was negative, and PD-L1 expression was below 1%. Next-generation sequencing did not identify driver genes. Tissue and blood tumor mutational burden were high at 30.9 and 39.1 mutations/Mb, and PET showed no disease outside the thorax. The diagnosis was left lung poorly differentiated adenocarcinoma, T3N2M1 Stage IV, with bilateral intrapulmonary, mediastinal, and right hilar lymph-node metastases. Although standard guidance would usually favor immunotherapy plus platinum chemotherapy, his team chose pembrolizumab monotherapy because of the high TMB and immune-profile findings. He received pembrolizumab 200 mg every 3 weeks. After 2 cycles, imaging was mixed but blood TMB and ctDNA decreased, so treatment continued. After 5 months, the lung mass and bilateral nodules had markedly reduced and nearly disappeared; blood TMB became undetectable and ctDNA cleared. This response was notable because PD-L1 expression was negative and CD8-positive T cells were sparse, while high TMB and NK-cell infiltration may have supported immunotherapy sensitivity. He remained on pembrolizumab without reported adverse events, and his NSCLC was considered a clinical complete remission by RECIST.