High-dose methotrexate dosing strategy in primary central nervous system lymphoma

Leuk Lymphoma. 2022 Jun;63(6):1348-1355. doi: 10.1080/10428194.2021.2024818. Epub 2022 Feb 4.

Abstract

The backbone induction therapy for primary central nervous system lymphoma (PCNSL) is high dose methotrexate (HD-MTX) and rituximab, which can be combined with other chemotherapeutic agents. The optimal dose of HD-MTX remains unclear, as doses between 3 and 8 g/m2 have been shown to be effective. In this retrospective study, HD-MTX dosed at 3-5 g/m2 demonstrated an overall response of 81.8%, with 11 (50%) complete responses. The median overall survival was not met at 29 months and median progression free survival was 12.5 months.There were two discontinuations due to nephrotoxicity. The most common adverse event was hepatotoxicity (18.5%), with no treatment-related mortality events observed.Overall, HD-MTX dosed at 3-5 g/m2 demonstrated similar efficacy and lower toxicity compared to higher doses in PCNSL patients. Reducing the initial HD-MTX dose may help ensure tolerability and completion of induction therapy, especially in patients with co-morbidities or older age who have poorer outcomes.

Keywords: Cancer; high-dose methotrexate; methotrexate; primary central nervous system lymphoma; rituximab.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Central Nervous System
  • Central Nervous System Neoplasms* / diagnosis
  • Central Nervous System Neoplasms* / drug therapy
  • Humans
  • Lymphoma* / diagnosis
  • Lymphoma* / drug therapy
  • Methotrexate / therapeutic use
  • Retrospective Studies

Substances

  • Methotrexate