The impact of tislelizumab immunotherapy on multiple primary lung cancer presenting as ground-glass nodules: preliminary results analysis from a single-arm, phase II trial.

BACKGROUND: The incidence of multiple primary lung cancer (MPLC) continues to increase, with synchronous multifocal ground-glass nodules (GGNs) representing a characteristic manifestation. In this study evaluated the efficacy and safety of tislelizumab in patients with MPLC who presented with synchronous multifocal GGNs were evaluated. METHODS: In this single-arm, phase II exploratory trial, 12 patients with synchronous multifocal GGNs were enrolled. All patients received at least two doses of tislelizumab (200 mg i.v., Q3W). The primary endpoint was the objective response rate (ORR). Multiplexed immunofluorescence (mIF), T-cell receptor sequencing (TCR-seq), and whole-exome sequencing (WES) were performed to investigate alterations in the tumor immune microenvironment (TIME) during immunotherapy. RESULTS: None of the 12 patients had lesions meeting the criteria for complete response (CR) or partial response (PR). One patient developed pseudoprogression (PsP), while one patient developed a new GGN during follow-up. The remaining 10 patients manifested stable disease (SD). No patients experienced grade 3-5 adverse events. mIF revealed significant differences in the TIME between PsP lesions and responsive lesions, characterized by increased CD8+ T-cell infiltration concurrent with heightened infiltration of immunosuppressive cells. TCR-seq analysis indicated that PsP lesions exhibited low clonality but high diversity. Furthermore, WES analysis demonstrated high heterogeneity among multiple lesions, with PsP lesions exhibiting a low tumor mutational burden (TMB). CONCLUSION: Patients with synchronous multifocal GGNs exhibited poor therapeutic responses to tislelizumab. Immune checkpoint inhibitors (ICIs) may induce PsP in pure GGNs, thereby leading to unnecessary extension of surgical resection, hence ICIs should be applied with caution in clinical management strategies.