Central Nervous System Prophylaxis Approach in High-Risk Diffuse Large B-Cell Lymphoma Patients: A Retrospectively...

Recent advances in the prevention of diffuse large B-cell lymphoma (DLBCL) have considerably focused on optimal strategies for preventing its recurrence in the central nervous system (CNS) in patients. This retrospective study aimed to assess the protective efficacy of intravenous high-dose methotrexate (HD-MTX) regimens in newly diagnosed patients with DLBCL presenting a high risk for CNS recurrence.

A total of 136 newly diagnosed high-risk DLBCL patients (HD-MTX group: n = 46; non-HD-MTX group: n = 90) were enrolled in this retrospective study. The primary endpoints included CNS recurrence rate, progression-free survival (PFS), overall survival (OS), and toxicity.

The 2-year CNS recurrence rates (median follow-up period: 25.5 months; 95% confidence interval: 21.0-30.0) were 4.3% and 11.1% in the HD-MTX and non-HD-MTX groups (p = 0.337), respectively. Additionally, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 70.7% versus 60.8% and 72.9% versus 60.8% (p = 0.013 and p = 0.024), respectively. The subgroup analysis for PFS and OS revealed that patients classified as the National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) low- or intermediate-risk, at a younger age, and without B symptoms demonstrated potential benefits from the HD-MTX treatment. In total, 46 patients completed 92 cycles of HD-MTX treatment, of which, 49 cycles were administered on day 6 of the R-CHOP regimen, with an average delay of no more than 4 days. In contrast, the remaining 43 cycles were initiated on days 10-14 following the completion of the R-CHOP regimen, with an average delay of 15 days. Interestingly, the incidence of hematological or non-hematological toxicity did not differ significantly among the groups.

Owing to the lack of robust evidence, the role of HD-MTX in preventing CNS recurrence could not be conclusively determined. Nevertheless, some patients could tolerate the treatment, such as younger individuals and those at NCCN-IPI low or intermediate risk, suggesting the efficacy of intravenous HD-MTX administration on day 6 as an optimal strategy for preventing CNS recurrence of DLBCL.