Pooled analysis of high-dose methotrexate as CNS prophylaxis in ultra high-risk large B-cell lymphoma

In large B-cell lymphoma (LBCL), use of high-dose methotrexate (HD-MTX) to prevent CNS relapde (‘CNS prophylaxis’) remains controversial. Pooled analysis of two retrospective studies examined the impact of HD-TMX in LBCL patients deemed ultra high-risk (UHR) due to CNS prognostic index score 5-6, and/or testicular, renal/adrenal, or breast involvement, and/or 3 or more extranodal sites. The primary outcome was CNS relapse (isolated or concurrent with systemic relapse) measured from diagnosis. Analyses were performed on 1923 patients meeting UHR criteria. No significant difference in 3-year CNS relapse rate was observed between 1051 patient receiving no HD-MTX versus 872 patients receiving HD-MTX after adjusting for baseline characteristic (9.3% versus 8.1%; aHR 1.13; 95% CI 0.82-1.57). Analysis restricted to isolated CNS relapse also confirmed no difference (5.9% versus 5.7%; aHR 1.03; 95% CI 0.69-1.53). In landmark analysis of all patients with no progression at 6 months (no HD-MTX n=782, HD-MTX n=773) no difference in 3-year CNS relapse was observed (6.7% versu 6.6%; aHR 0.95; 95% CI 0.62-1.44). The authors conclude that use of HD-MTX did not improve CNS relapse in UHR LBCL.