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The authors of this multicenter, retrospective study evaluated the impact of prophylactic intravenous high-dose methotrexate (HD-MTX) on the risk of CNS relapse among 906 patients with diffuse large B-cell lymphoma (DLBCL). After a median follow-up of approximately 3 years, the CNS relapse rates were 1.9% for CNS-IPI score 0–1, 4.9% for CNS-IPI score 2–3, and 12.2% for CNS-IPI score 4–6. Among high-risk patients, 35% received HD-MTX. There was no significant difference in CNS relapse rates between those who did or did not receive HD-MTX. Patients who received more intensive chemotherapy had a lower risk of CNS relapse.
Due to the retrospective nature of this study, hematologists/oncologists currently using HD-MTX in the high-risk patient population are unlikely to change their practice despite the results being contradictory to those reported in previous smaller studies.
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 2012-2019. 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<0.0001). 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 4 (3.5%) had testicular lymphoma. The median number of HD-MTX doses was 2 (range 1-3). CNS relapse risk was similar with versus without HD-MTX (11.2% vs. 12.2%, p=0.82) 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. This article is protected by copyright. All rights reserved.