Retrospective Review of the Safety and Efficacy of High-Dose Methotrexate for Prevention of CNS Relapse in Diffuse Large B-Cell Lymphoma at Kaiser Permanente- Northern California (Jan 2015 - June 2019)
Authors: Law Lisa Y , Dutia Mrinal , Stevenson Ryan , Lau Melanie , Mok Timothy , Vu Khoan , Soe Aye Min , Lopez Alfredo R. , Thomas Sachdev , Vempaty Hyma T. , Gavini Aruna , Nair Bijay 
Published: November 2021

Abstract
Retrospective review of the safety and efficacy of high-dose methotrexate for prevention of CNS relapse in diffuse large B-cell lymphoma at Kaiser Permanente- Northern California (Jan 2015 - June 2019)

Background: Central nervous system (CNS) relapse occurs in 10-12% of high-risk diffuse large B-cell lymphoma (DLBCL) patients. Prophylactic intravenous high-dose methotrexate (HD-MTX) is recommended by international guidelines to reduce this risk despite limited evidence to support such practice. Recent retrospective studies have cast doubt on the clinical benefit of such treatment. There is limited data on safety and efficacy of such treatment in a community oncology setting.
Methods: We conducted a retrospective analysis of adults ≥ 18 years diagnosed with DLBCL treated with systemic therapy and HD-MTX as CNS prophylaxis at Kaiser Permanente Northern California from 1/2015 - 6/2019. We abstracted patient demographics, clinical information, treatment, toxicity, and health care utilization from the electronic health record. Descriptive statistics were used to evaluate patients' outcomes.
Results: Of 33 patients (median age: 61; range: 23 - 81; age ≥ 60: 57.5%), most had stage IV disease (78.7%) and an ECOG performance status of 0 or 1 (66.5%). Patients with CNS-IPI score of 2-3 (intermediate-risk) was 30.3%, while higher CNS-IPI scores of 4-6 (high-risk) was 51.5%. Other patient characteristics include double hit lymphoma (12.1%), kidney/adrenal gland involvement (33%), and/or epidural involvement (24.2%). Most common therapies were R-CHOP (51.5%) and R-EPOCH (27.2%). The median number of HD-MTX doses was 3 (range 1-4). The median cumulative dose was 7 gm/m2 (range 3-10.5). With regards to the treatment schedule, 63.6% received HD-MTX intercalated with systemic chemotherapy and 36.4% received HD-MTX after completion of preplanned treatment. Overall, renal toxicity was the most common adverse side effect. The rates of grade 1, 2 and 3 renal toxicity were 12.1%, 9% and 6%, respectively. Other notable side effects experienced were neutropenic fever requiring hospitalization (27.2%) and grade 3 transaminitis (6%). No patients experienced grade 3 mucositis. The median duration of hospital stay was 12 days (range 4-37) and 12.1% required suspension of future HD-MTX. With a median follow up of 31.3 months (range: 0.79 - 58.4) 69.6% are alive and 15.1% had CNS relapse despite prophylactic HD-MTX.
Conclusions:
In this community oncology setting, patients with DLBCL who were deemed high risk for CNS relapse and received HD-MTX for prophylaxis experienced similar CNS relapse rate compared to those who did not in previous studies. Our findings are in line with recent retrospective reviews, which further support the lack of benefit of such prophylactic treatment. This study underscores the need for further research to prevent CNS disease and improved patient selection criteria for prophylactic treatment among high risk DLBCL patients.

Disclosures
No relevant conflicts of interest to declare.