LAUSR

Central nervous system (CNS) relapse affects 5% of diffuse large B‐cell lymphoma (DLBCL) patients and portends a poor prognosis. Prophylactic intravenous high‐dose methotrexate (HD‐MTX) is frequently employed to reduce this risk, but there is limited evidence supporting this practice. We conducted a multicenter retrospective study to determine the CNS relapse risk with HD‐MTX in DLBCL patients aged 18–70 years treated in Alberta, Canada between 2012 and 2019. Provincial guidelines recommended HD‐MTX for patients at high‐risk of CNS relapse based upon CNS‐IPI score, double‐hit lymphoma, or testicular involvement. Among 906 patients with median follow‐up 35.3 months (range 0.29–105.7), CNS relapse occurred in 1.9% with CNS‐IPI 0–1, 4.9% with CNS‐IPI 2–3, and 12.2% with CNS‐IPI 4–6 (p < .001). HD‐MTX was administered to 115/326 (35.3%) high‐risk patients, of whom 96 (83.5%) had CNS‐IPI score 4–6, 45 (39.1%) had double‐hit lymphoma, and four (3.5%) had testicular lymphoma. The median number of HD‐MTX doses was two (range 1–3). Central nervous system relapse risk was similar with versus without HD‐MTX (11.2% vs. 12.2%, p = .82) and comparable to previous reports of high‐risk patients who did not receive CNS prophylaxis (10–12%). In multivariate and propensity score analyses, HD‐MTX demonstrated no association with CNS relapse, progression‐free survival, or overall survival. This study did not demonstrate a benefit of prophylactic HD‐MTX in this high‐risk patient population. Further study is required to determine the optimal strategy to prevent CNS relapse in DLBCL.