In this PACULit episode, Britany and Seth discuss a prospective single-arm study of autologous NK cells plus the PD-1 inhibitor Sintilimab as second-line therapy for advanced non-small cell lung cancer without driver mutations after platinum chemotherapy failure. The 20-patient trial reports a median overall survival of 27.3 months, with six patients alive at data cutoff, marking improvement over the earlier pilot data of 17.7 months. The discussion highlights predictive biomarkers such as CD56+PD-L1+ NK cells and ctDNA clearance, the latter associated with a 93% reduction in death risk (hazard ratio 0.07). Safety was reassuring, with no new or increased adverse events. The episode also covers the biological rationale for combining NK cells with PD-1 blockade, comparisons to pembrolizumab-based combinations, and limitations including small sample size and lack of a control arm, underscoring the need for randomized trials and standardization of NK cell manufacturing. Real-time ctDNA monitoring is presented as a potential early indicator of response, illustrating the broader potential of integrating innate and adaptive immunity in NSCLC.
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