Investigating multi-agent intrathecal chemotherapy as a treatment for primary and secondary central nervous system lymphoma: safety and efficacy results from an institutional cohort study

Abstract INTRODUCTION Despite exquisite responses to initial therapy for CNS lymphoma, relapse is common and overall responses are disappointing compared to non-CNS diffuse large B-cell lymphomas. Literature reports 1 and 3 year survival rates of 50% and 30-40% respectively, with standard treatment. Intravenous, high-dose-methotrexate-based therapies have become the standard of care, with many variations but no consensus. Incorporation of multi-agent intrathecal chemotherapy (MAITC) alongside systemic therapy is novel but not widely adopted. We report our institutional data on safety and efficacy of MAITC in CNS lymphoma. METHODS A retrospective review of patients with primary or secondary CNS lymphoma, treated with MAITC between August 2015 and December 2021, was conducted. Each cycle includes alternating combinations of 2-3 of the following drugs: methotrexate, rituximab, cytarabine, etoposide, topotecan, gemcitabine, and thiotepa, via ommaya reservoir. Log-rank tests and Cox regression were used to evaluate survival differences. RESULTS 59 patients were reviewed (21 primary; 38 secondary CNS lymphoma). Median age at start of MAITC was 66 years (range 25-90). Only six patients received external beam radiation (EBRT). Median MAITC cycles was 8 (range 2-23). 76% of patients with primary and 66% with secondary CNS lymphoma were alive 1 year after starting MAITC. Of 37 eligible patients, 17 (46%) were alive 3 years after starting MAITC. After a median 19.2 months follow-up, median OS was not reached. No significant difference was noted in OS between primary and secondary CNS lymphoma. KPS > 80 was positively while leptomeningeal disease, secondary CNS lymphoma, and EBRT were negatively associated with OS. Ommaya-related infections occurred in 8 patients (13.5%); only 1 required removal. CONCLUSION Based on our institutional data, MAITC can potentially offer a significant OS advantage with minimal safety concerns. Factors associated with poor survival were identified, which are being addressed in a larger dataset along with baseline CSF biomarkers.