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

• Published in: American journal of hematology 2015-12, Vol.90 (12), p.1149-1154
• Main Authors: Kansara, Roopesh, Shenkier, Tamara N., Connors, Joseph M., Sehn, Laurie H., Savage, Kerry J., Gerrie, Alina S., Villa, Diego
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.24204

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/m2 every 2 weeks, to best response or 10 cycles. After 2006, rituximab 375 mg/m2 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. Am. J. Hematol. 90:1149–1154, 2015. © 2015 Wiley Periodicals, Inc.