Long-Term Response to PD-1 and CTLA-4 Blockade in an SCLC Patient with Negative PD-L1 Expression on Biopsy: A Case Report

Abstract

Despite recent advances in the availability of new therapeutic agents, small-cell lung cancer (SCLC) remains an aggressive disease with a poor prognosis. While immune checkpoint inhibition has revolutionized the treatment of non-small cell histologies, results in SCLC have shown overall less favorable evolution, and despite initial data from different trials showing potential for development, the lack of reliable biomarkers for patient selection is a major hindrance to their use. Most notably, programmed death-ligand 1 (PD-L1) expression does not appear to play a key role in SCLC responsiveness to immune checkpoint inhibition. While other biomarkers such as tumor mutational burden (TMB) have been suggested to be more relevant, literature data are not univocal on this subject. We report here on a 58-year-old patient with metastatic PD-L1-negative SCLC treated in an advanced and symptomatic setting who obtained a complete and sustained clinical and radiological response to the combination of nivolumab and ipilimumab. We also discuss the impact of treatment-related adverse events, such as autoimmune hypothyroidism, gastroenteric toxicity and pneumonitis, on his quality of life. This case, while it exemplifies the potential of immune checkpoint inhibition in SCLC, highlights the need for a deeper understanding of the mechanisms underlying its efficacy in order to identify patients who are more likely to benefit from treatment.