P11.27.B EXPLORATORY STUDY ON INTRAVENTRICULAR ADMINISTRATION OF NIVOLUMAB VIA OMMAYA RESERVOIR FOR LEPTOMENINGEAL METASTASES FROM LUNG CANCER: A RETROSPECTIVE ANALYSIS OF 12 CASES

Abstract BACKGROUND Leptomeningeal metastases (LM) from lung cancer carry a dismal prognosis, particularly in patients who develop resistance to standard intraventricular chemotherapy with pemetrexed. Although intraventricular pemetrexed via an Ommaya reservoir has demonstrated clinical benefit, its efficacy is limited in cases of primary or acquired resistance. This exploratory study aims to assess the safety and preliminary efficacy of intraventricular nivolumab (40 mg) in patients with LM from lung cancer who are refractory to pemetrexed. MATERIAL AND METHODS From October 2022 to December 2025, 12 patients with LM secondary to lung cancer were retrospectively reviewed at the Department of Neurosurgery, Fudan University. All patients had demonstrated resistance to intraventricular pemetrexed: 3 with primary resistance (disease progression within 1 month of initiation) and 9 with acquired resistance (progression after more than 1 month of therapy). Each patient received 40 mg of nivolumab via intraventricular injection through an Ommaya reservoir. For patients showing initial clinical benefit, treatment was continued every 3 weeks. Efficacy was evaluated based on neurological symptom improvement, thin-slice cranial MRI (including black-blood sequences), cerebrospinal fluid (CSF) cytology, and biochemical parameters. The intraventricular administration protocol was approved by the institutional ethics committee, and all patients receiving treatment provided written informed consent. RESULTS Among the 3 patients with primary resistance, 1 patient exhibited a meaningful clinical response, with progression-free survival (PFS) of 6 months and ongoing disease control. Of the 9 patients with acquired resistance, 4 demonstrated a favorable response: 2 patients with PFS of 4 months and 2 with PFS of 1 month. The remaining 7 patients (2 with primary and 5 with acquired resistance) experienced no significant symptomatic improvement and were classified as treatment non-responders. No serious adverse events related to intraventricular nivolumab administration were observed. CONCLUSION Intraventricular administration of nivolumab via an Ommaya reservoir appears to be a feasible and potentially effective salvage therapy for lung cancer patients with leptomeningeal metastases refractory to pemetrexed. These preliminary findings warrant further validation in prospective studies with larger patient cohorts to better define its clinical utility and appropriate patient selection.