High-Dose Methotrexate as CNS Prophylaxis in Ultra High-Risk Large B-Cell Lymphoma: An International Multicenter Analysis

High-dose methotrexate given as central nervous system prophylaxis did NOT reduce CNS relapse in patients with ultra high-risk large B-cell lymphoma: the 3-year CNS relapse rate was 8.1% with methotrexate versus 9.3% without it (adjusted HR 1.13; 95% CI 0.82-1.57). This is the largest international comparative dataset in this population to date (n=1,923). The finding held when restricted to isolated CNS relapse (5.7% vs 5.9%; HR 1.03; 95% CI 0.69-1.53) and in a 6-month landmark analysis (6.6% vs 6.7%; HR 0.95; 95% CI 0.62-1.44). International guidelines still recommend this prophylaxis in ultra high-risk patients precisely because robust data have been lacking; the analysis is retrospective, which the authors note as a limitation.