Rituximab with high-dose methotrexate in primary central nervous system lymphoma

Am J Hematol. 2015 Dec;90(12):1149-54. doi: 10.1002/ajh.24204. Epub 2015 Nov 17.

Abstract

The addition of rituximab (R) to chemotherapy improves outcomes in patients with systemic B-cell non-Hodgkin lymphomas, but the impact in patients with primary central nervous system lymphoma (PCNSL) receiving high-dose methotrexate (HDMTX) is unknown. Patients diagnosed with PCNSL at the British Columbia Cancer Agency (BCCA) between 2000 and 2013 were treated with ≥1 cycle of HDMTX 8 g/m(2) every 2 weeks, to best response or 10 cycles. After 2006, rituximab 375 mg/m(2) was given every 2 weeks with HDMTX for a total of 4 doses. 49 (66%) patients received HDMTX alone and 25 (34%) HDMTX+R, with a median of 5 (range 1-10) HDMTX cycles, and no difference between groups. The median follow-up was 5 years: 8.8 years (range 3.15-13.5 years) HDMTX and 1.9 years (range 0.5-7 years) HDMTX+R. The 5-year PFS was 17%, with no difference between groups (HR: 0.75, 95% CI: 0.41-1.35; P = 0.33). The 5-year OS was 38%, with no difference between the groups OS (HR: 0.73, 95% CI: 0.35-1.52; P = 0.39). In this retrospective study comparing two subgroups of patients treated in different eras, the addition of R to HDMTX did not appear to improve outcomes in PCNSL, possibly consistent with its known poor CNS penetration. It is possible that with a larger sample size, longer follow-up, or different rituximab dosing/schedule, the addition of rituximab may lead to a statistically significant improvement in outcomes. Prospective randomized trials currently in progress will more definitively estimate the impact of the addition of rituximab to HDMTX-based chemotherapy for PCNSL.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Central Nervous System Neoplasms / drug therapy*
  • Female
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Rituximab / administration & dosage
  • Rituximab / therapeutic use*
  • Young Adult

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Rituximab
  • Methotrexate