Prophylaxis with high-dose methotrexate suppresses isolated CNS relapse risk in DLBCL

High-dose methotrexate (HDMTX) helps prevent isolated central nervous system (CNS) relapse in patients with diffuse large B cell lymphoma (DLBCL), a recent study has found. On the other hand, HDMTX seems to have no impact on systemic CNS relapse, systemic relapse, or survival.

Researchers conducted a retrospective study of 226 patients with newly diagnosed DLBCL deemed high-risk by the CNS International Prognostic Index. The primary outcomes were the time to CNS relapse, either isolated or concomitant with systemic disease, and systemic relapse. CNS relapse was detected using cerebrospinal fluid cytology or flow cytometry, or brain/vitreous biopsy.

Isolated CNS relapse occurred in 24 patients, systemic-only recurrence in 43, and concomitant relapse in 10. The median times to the respective relapse endpoints were 7, 8, and 10 months. Median overall survival (OS) after CNS (isolated and concomitant systemic) relapse was 63 days, with 23 deaths (68 percent). The median OS after systemic relapse was 121 days, with 22 patients dying (65 percent).

Sixty-six (29.2 percent) patients received prophylactic HDMTX, delivered at ≥3-g/m² doses in 81 percent of cycles. Multivariable Cox proportional hazards analysis found that HDMTX prophylaxis significantly reduced the risk of isolated CNS relapse (hazard ratio [HR], 0.16, 95 percent confidence interval [CI], 0.03–0.91; p=0.039), an effect that remained significant even after propensity score matching (HR, 0.06, 95 percent CI, 0.004–0.946; p=0.046).

On the other hand, such prophylaxis yielded no significant benefit for systemic relapse (p=0.129), progression-free survival (p=0.818), or OS (p=0.332).