Optimization of high-dose methotrexate prophylaxis for central nervous system relapse in diffuse large B-cell lymphoma: a multicenter analysis

• Published in: Annals of hematology 2022-03, Vol.101 (3), p.595-605
• Main Authors: Fang, Yu, Su, Ning, Ma, Shuyun, Cai, Jun, Zhong, Liye, Li, Wenyu, Huang, Huiqiang, Li, Zhiming, Huang, He, Xia, Yi, Liu, Panpan, Guo, Linlang, Li, Zhihua, Wu, Yudan, Tian, Xiaopeng, Wang, Jinni, Zhang, Yuchen, Cai, Qingqing
• Format: Article
• Language: English
• Subjects: Aged; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - therapeutic use; Central Nervous System Neoplasms - drug therapy; Central Nervous System Neoplasms - secondary; Chemotherapy; Disease prevention; Female; Follow-Up Studies; Hematology; Humans; Induction therapy; Lymphoma; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Medicine; Medicine & Public Health; Methotrexate - administration & dosage; Methotrexate - therapeutic use; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - secondary; Nervous system; Oncology; Original Article
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-021-04739-x

Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare but devastating event. Intravenous high-dose methotrexate (HD-MTX) is recommended as CNS prophylaxis, but the optimal timing and dose has not been elucidated. Here, we report a multicenter analysis of prophylactic HD-MTX administration for DLBCL. Two hundred eighty-four patients receiving HD-MTX either concurrent with each induction chemotherapy cycle ( n  = 221) or at the end of induction therapy (EOI, n  = 63) were included. Patients with CNS-IPI scoring 4–6, and/or testicular involvement, and/or double/triple hit lymphoma, were stratified into the high-risk group and the others into the moderate-risk group. Concurrent HD-MTX was associated with increased risk of grade 3/4 treatment-related toxicity (OR,1.49; P  = 0.006) and subsequent chemotherapy delays (OR, 1.87; P  = 0.003) in multivariate analysis. With a median follow-up of 36.0 months, no significant difference in CNS relapse rate was identified between the concurrent and EOI groups (3.2% vs 4.8%, P  = 0.34), even in the high-risk group. Analysis on systemic MTX dose suggested that high-dose MTX (≥ 2 g/m 2 ) was associated with better CNS relapse control only in the high-risk group, but not in the moderate-risk group. This study may elucidate the superiority of EOI HD-MTX to some extent. High MTX dose (≥ 2 g/m 2 ) may not be necessary for the moderate-risk patients.