ABCL-241: Comparing Efficacy of Intrathecal Chemotherapy versus High-Dose Methotrexate for Central Nervous System Prophylaxis in High-Grade B-Cell Lymphomas

Abstract

Context Outcomes of patients with high-grade B-cell lymphomas have improved with chemoimmunotherapy. However, some patients are at an increased risk of developing secondary central nervous system (CNS) relapse, associated with increased morbidity. Objective The objective of this study was to analyze the efficacy of intrathecal chemotherapy versus high-dose methotrexate for the prevention of secondary CNS relapse in high-grade B-cell lymphoma patients. Design This was a single-institution, retrospective cohort study. A report was created via electronic health records to identify patients that received CNS prophylaxis with a confirmed diagnosis of high-grade B-cell lymphoma from January 2017 to September 2020. Setting This study took place at a general community hospital. Patients or Other Participants Inclusion criteria included age > 18 years, histologically confirmed high-grade B-cell lymphoma, either R-CHOP or DA-R-EPOCH as the primary chemoimmunotherapy regimen, and no CNS involvement at the time of diagnosis. Interventions Arm A included 11 patients that received intrathecal chemotherapy, and arm B included 11 patients that received intravenous high-dose methotrexate for prophylaxis. Main Outcome Measures The primary outcome of this retrospective study was to assess rates of CNS relapse, with a median follow-up of 1 year since diagnosis. Secondary outcomes included progression-free survival (PFS), overall survival (OS), toxicity, cost of care, and delays in therapy between both arms. Results Development of secondary CNS relapse occurred in 2 (18.2%) of the patients in arm A and 2 (18.2%) in arm B, which was not statistically significant by Chi-square analysis with Yates correction (p=.58042). PFS was consistent between both arms at 72.7%. One-year OS for each arm was 90.9% vs 72.7%, (p=.0887). Toxicity developed in 36% of high-dose methotrexate patients. Two patients needed a dose reduction of high-dose methotrexate, and two had delays in further cycles of primary chemoimmunotherapy regimen. High-dose methotrexate was associated with a significantly higher cost on average per cycle. Conclusions There was no statistically significant difference in the development of secondary CNS relapse between intrathecal chemotherapy and high-dose methotrexate. Further prospective, randomized studies are needed to assess if CNS prophylaxis improves outcomes and which method of prophylaxis is more efficacious.