The following is a summary of “High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma,” published in the December 2023 issue of Oncology by Lewis, et al.

CNS progression or relapse is a rare but severe complication in aggressive B-cell lymphoma, and the optimal approach to CNS prophylaxis remains uncertain. For a study, researchers sought to assess the effectiveness of high-dose methotrexate (HD-MTX) in preventing CNS progression in patients at high risk of this complication.

Included were patients aged 18-80 with aggressive B-cell lymphoma and a high risk of CNS progression, treated with curative-intent anti–CD20–based chemoimmunotherapy. The retrospective, international, observational study calculated cause-specific hazard ratios (HRs) and cumulative risks of CNS progression based on HD-MTX use. Time to CNS progression was assessed from diagnosis for all patients and completion of frontline systemic lymphoma induction therapy for patients in complete response at chemoimmunotherapy completion.

A total of 2,418 all patients (HD-MTX; n = 425) and 1,616 complete response patients (HD-MTX; n = 356) were included. In 83.4% of all patients, the CNS International Prognostic Index was 4-6. Those treated with HD-MTX showed a lower risk of CNS progression (adjusted HR, 0.59 [95% CI, 0.38 to 0.90]; P = .014). However, significance was not maintained in complete response patients (adjusted HR, 0.74 [95% CI, 0.42 to 1.30]; P = .29), with a 5-year adjusted risk difference of 1.6% (95% CI, –1.5 to 4.4; all patients) and 1.4% (95% CI, –1.5 to 4.1; complete response patients). The study lacked the power to draw definitive conclusions for specific high-risk scenarios, and there was no clear reduction in CNS progression risk with HD-MTX in any high-risk subgroup.

In the extensive study, high-risk patients receiving HD-MTX had a 7.2% 2-year risk of CNS progression, consistent with previously reported high-risk cohorts. The use of HD-MTX did not exhibit a clinically meaningful reduction in the risk of CNS progression.

Source: ascopubs.org/doi/full/10.1200/JCO.23.00365