Delayed Methotrexate Elimination Following High-dose Methotrexate Prophylaxis in High-risk Diffuse Large B-cell Lymphoma

Objective High-dose methotrexate (HD-MTX) is widely used as central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL) who are at a high risk of CNS relapse. Ensuring safe prophylactic administration with minimal adverse events is a key concern; however, few studies have detailed the safety profile of HD-MTX prophylaxis in patients with high-risk DLBCL. We analyzed the adverse events associated with HD-MTX in this population, focusing on delayed MTX elimination. Methods This multicenter retrospective study included 98 patients with DLBCL at high risk of CNS relapse who received HD-MTX as part of frontline therapy between 2014 and 2020. CNS prophylaxis involved 2 cycles of HD-MTX (3.0 g/m²) at 2-week intervals. Results The median age at the diagnosis was 63 (34-84) years old, and 34 patients received a reduced methotrexate (MTX) dose. The overall incidence of delayed MTX elimination was 18.4%. No cases of delayed MTX elimination were observed in the group that received a 3-h MTX infusion (n=50). Toxicities were more frequent in patients with delayed MTX elimination than in those without (77.8% vs. 26.2%, p≤0.05), including higher incidences of grade ≥3 adverse events and grade ≤2 renal dysfunction. Conclusion Delayed MTX elimination is associated with increased complications. Shorter MTX infusion rates, particularly at 3 h, may reduce the risk of delayed MTX elimination.