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Background: Leptomeningeal metastasis (LM) is a serious complication of advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation. There are no guidelines or consensus on the optimal treatment regimens and strategies for LM yet. Objectives: To analyze the influence of different treatment methods on the survival of patients and explore the factors influencing the prognosis of patients with LM. We profiled the cerebrospinal fluid (CSF) immune microenvironment in patients with LM using genetic and lymphocyte subset analyses. Design: We identified 209 patients with advanced NSCLC who developed LM without extracranial progression following third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKIs) therapy. Their medical records were reviewed to extract relevant data. Methods: Survival curves were plotted and prognostic factors were analyzed using R software and SPSS statistical software, respectively. Statistical analysis was performed on the results of CSF genetic testing and lymphocyte subset profiling. Results: The median overall survival (mOS) time of patients who received high-dose EGFR-TKI monotherapy or in combination with other treatments was longer than that of patients with standard-dose EGFR-TKI combined with other treatments (19.7 vs 9.0 months), patients who received EGFR-TKI combined with anti-angiogenic drugs was longer than that of patients who did not combine anti-angiogenic drugs (19.6 vs 12.0 months). Analysis of CSF genomic profiles from 124 patients with LM identified a greater frequency of EGFR L858R (64.5%) versus exon 19 deletions (35.5%). We also observed a significant enrichment of B-cell subsets in the CSF of patients with LM compared to those without, and the B-cell count gradually decreased during the treatment process. Conclusion: For patients developing LM after third-generation EGFR-TKI resistance, high-dose EGFR-TKIs or EGFR-TKIs combined with anti-angiogenic drugs represent viable therapeutic strategies, and B lymphocytes may serve as a promising immunotherapy target for LM.
Yun et al. (Mon,) studied this question.