Mmap-06 Intrathecal Chemotherapy as Part of a Multimodal Approach for the Treatment of Leptomeningeal Metastases

Abstract INTRODUCTION Leptomeningeal Metastases (LM) is a devastating complication of advanced cancer with historically poor outcomes. Median overall survival (OS) has typically ranged from 2–4 months, although recent advances in craniospinal irradiation (CSI) and newer systemic chemotherapies are improving outcomes. We evaluated the role of intrathecal chemotherapy (IT) on overall survival, for the treatment of LM, as part of multimodal approaches with systemic chemotherapy and radiation. METHODS We retrospectively evaluated treatment patterns and survival in 60 patients with metastatic carcinoma who received IT for LM, from 2016-2024. All patients underwent Ommaya reservoir placement and received IT. RESULTS The median age at LM diagnosis was 53.5 years. 50/60 were female. Histologies were as follows: Breast cancer (n=36), Lung cancer (n=18), Other (n=6). 40/60 also received involved-field RT to brain or spine, 7/60 received CSI. 46/60 had a change in their systemic chemotherapy regimen. The median OS for all patients was 13 months (breast 12 months, lung 10.5 months, other 5 months). Kaplan-Meier analysis demonstrated that patients who received CSI at any recurrence (n=8) had a trend for better survival, with a hazard ratio (HR) of 0.21 (95% CI: 0.03–1.55, p=0.127, median OS not reached). Patients who had a change in systemic chemotherapy had a median OS of 10.5 months, vs 8 months when prior systemic treatment was continued. Additionally, we evaluated patients who did not receive antibody-drug conjugates after LM diagnosis or CSI, which can improve OS, and the median OS of this group was still 10.5 months (n=38). Initial Karnofsky Performance Status (KPS) was borderline significant in predicting improved OS, (HR = 0.98, 95% CI: 0.96–1.00, p=0.059). CONCLUSION These findings suggest that the inclusion of IT chemotherapy in multimodal treatment strategies may meaningfully improve outcomes in LM, especially when accompanied by CSI and changes in systemic chemotherapy.