Exceptional Long-term Response to Immunotherapy in an African American Man With <i>STK11/TP53/RB1</i> -Mutated Metastatic Lung Adenocarcinoma

Immunotherapy has become the standard of care for advanced and resectable lung cancer, and specific mutations may predict immunotherapy response. For example, <i>STK11</i> mutations, which are more common in African American patients, are associated with immunotherapy resistance. A 68-year-old African American man with stage IIIB lung adenocarcinoma with mediastinal lymph node involvement progressed on first-line concurrent carboplatin-based chemoradiotherapy. Molecular testing of the patient's subcarinal lymph node tissue revealed <i>STK11</i> S216F, <i>TP53</i> R273L, and <i>RB1</i> splice site mutations; high tumor mutation burden (19.0 mutations/Mb); and high PD-L1 22c3 expression (TPS 70%, 2+ intensity). Treatment with carboplatin-based chemotherapy with radiation therapy failed to control the disease, but the patient has tolerated and responded well to intravenous pembrolizumab. Although <i>STK11</i> mutations are associated with immunotherapy resistance, our patient demonstrated an exceptional and sustained response to immunotherapy for over two years. The patient's <i>STK11/TP53</i> co-mutation, along with high TMB and PD-L1 22c3 TPS scores, may help explain his continued responsiveness to immunotherapy and longer survival. Importantly, incorporating genetic ancestry differences in mutation prevalence and the impact of specific mutations and co-mutations, may help ensure the equitable and optimal treatment of all patients with lung cancers.