Efficacy and safety of immunotherapy in locally advanced or metastatic pulmonary lymphoepithelioma-like carcinoma: a multicenter retrospective study.

BACKGROUND

Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare subtype of non-small-cell lung cancer that predominantly affects younger, non-smoking individuals in southern and southeast Asia, where Epstein-Barr virus (EBV) prevalence is high. The efficacy and safety of immunotherapy in pLELC, especially in second-line settings, remain inadequately explored.

OBJECTIVES

This study aimed to evaluate the efficacy of immunotherapy, either alone or in combination with chemotherapy, in improving progression-free survival (PFS) and overall survival (OS) in patients with advanced pLELC.

DESIGN

This was a multicenter retrospective study.

METHODS

A retrospective analysis was conducted on 252 patients with stage IIIB-IV pLELC treated across six centers. Patients received chemotherapy, immunotherapy, or a combination of both (chemoimmunotherapy). The primary outcomes measured were PFS and OS across different treatment regimens.

RESULTS

Chemoimmunotherapy significantly improved both PFS and OS compared to chemotherapy alone, in both first- and second-line settings. In first-line treatment, chemoimmunotherapy resulted in a median PFS of 17.6 months and OS of 26.1 months, compared to chemotherapy alone (PFS 8.7 months, OS 19.2 months). In the second-line setting, chemoimmunotherapy achieved a median PFS of 5.1 months and OS of 13.5 months, surpassing the outcomes with chemotherapy alone (PFS 3.3 months, OS 8.9 months). High baseline EBV-DNA levels (>2000 copies/mL) and low programmed death ligand 1 (PD-L1) expression (<50%) were associated with poorer outcomes. In addition, patients with high baseline serum tumor markers (STMs) and a dynamic reduction of ⩽20% in STMs exhibited significantly worse PFS and OS.

CONCLUSION

The study suggests that immunotherapy, particularly when combined with chemotherapy, offers significant survival benefits for patients with advanced pLELC. Baseline EBV-DNA levels, PD-L1 expression, and both baseline and dynamic STM changes serve as important predictors of treatment response, highlighting the need for personalized therapeutic approaches in this unique subtype of lung cancer.