High-Dose Methotrexate as CNS Prophylaxis in Ultra High-Risk Large B-Cell Lymphoma: An International Multicenter Analysis
- Author(s)
- Wilson, MR; Lewis, KL; Kirkwood, AA; Cwynarski, K; Cheah, CY; El-Galaly, TC; Villa, D; Savage, KJ; Ghione, P; Bobillo, S; Smedby, KE; Harrysson, S; Trneny, M; Klanova, M; Puckrin, R; Fox, CP; Bishton, M; Thanarajasingam, G; Wong Doo, N; Hapgood, G; Soussain, C; Choquet, S; Dickinson, M; Talaulikar, D; de Mel, S; Preston, G; Ahearne, M; Hawkes, EA; Schorb, E; Clavert, A; Ku, M; Guidetti, A; Narkhede, M; Calimeri, T; Durot, E; Smith, J; Renaud, L; McKay, P; Eyre, TA;
- Journal Title
- Journal of Clinical Oncology
- Publication Type
- Online publication before print
- Abstract
- PURPOSE: In large B-cell lymphoma (LBCL), use of high-dose methotrexate (HD-MTX) to prevent CNS relapse (so-called CNS prophylaxis) remains controversial. International guidelines continue to recommend HD-MTX in patients deemed ultra high risk (UHR) because of a lack of robust data specific to these subgroups. This study was designed to examine the impact of HD-MTX specifically in UHR patients. METHODS: Data from two previous retrospective analyses were combined to produce a cohort of UHR patients (≥1 of the following criteria: CNS international prognostic index score 5-6; testicular, renal/adrenal, or breast involvement; ≥3 extranodal sites), treated with or without HD-MTX. The primary outcome was CNS relapse rate (isolated or concurrent with systemic relapse) measured from diagnosis with additional landmark analysis of all responding patients with no progression event at 6 months. RESULTS: Analyses were performed on 1,923 patients meeting UHR criteria. No significant difference in 3-year CNS relapse rate was observed between no HD-MTX (n = 1,051) versus HD-MTX patients (n = 872), including in multivariable analyses adjusting for baseline characteristics (3-year rate, 9.3% v 8.1%; adjusted hazard ratio [HR], 1.13 [95% CI, 0.82 to 1.57]). Analyses restricted to isolated CNS relapse also confirmed no difference (5.9% v 5.7%; adjusted HR, 1.03 [95% CI, 0.69 to 1.53]). In the landmark analysis (no HD-MTX n = 782, HD-MTX n = 773), no difference in 3-year CNS relapse was observed (6.7% v 6.6%, adjusted HR, 0.95 [95% CI, 0.62 to 1.44]). CONCLUSION: To our knowledge, this is the largest international comparative data set of patients with LBCL with UHR features showing no significant reduction in CNS relapse with HD-MTX in all UHR or in any individual subgroup. Despite inherent limitations of retrospective analyses, the data strongly support previous studies in suggesting HD-MTX prophylaxis has no meaningful benefit for most patients.
- Department(s)
- Haematology
- Publisher's Version
- https://doi.org/10.1200/jco-26-00947
- Open Access at Publisher's Site
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Creation Date: 2026-07-02 01:34:30
Last Modified: 2026-07-02 01:34:39