A Real-World Experience With First-Line RTOG 0227 (Methotrexate, Temozolomide, and Rituximab) Induction for Primary CNS Lymphoma
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Published on: October 27, 2014
James J Fradin1, Ramsha Ahmed2, Precious Anyanwu3
1Department of Internal Medicine, Medical College of Wisconsin, Milwaukee, WI.
Background:
Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal lymphoma typically treated with CNS-penetrating induction therapy followed by consolidation. Multiple induction and consolidation strategies exist, including whole brain radiation therapy (WBRT), autologous stem cell transplantation (ASCT), novel/targeted agents, and conventional chemotherapy. The RTOG-0227 induction regimen (high-dose methotrexate, temozolomide, and rituximab [MTR] followed by WBRT) demonstrated favorable efficacy and tolerability in a phase I/II trial, with no treatment-related mortality. Real-world outcomes for MTR induction remain limited.
Objective:
To assess real-world outcomes of patients treated with MTR induction followed by either ASCT or WBRT consolidation.
Study Design:
We conducted a single-center retrospective study of adults with newly diagnosed PCNSL treated with MTR induction between 2017 and 2024. Patients subsequently underwent consolidation with ASCT or WBRT. Those who received WBRT continued with temozolomide maintenance. Outcomes included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Results:
Thirty-six patients were included in the analysis (median age 63 years). Following induction, ORR was 89%, with a complete response rate of 25%. Seventeen patients (47%) underwent ASCT and 18 (50%) received WBRT. At a median follow-up of 3.4 years, median OS was not reached, and median PFS was 6.0 years. For patients who responded to MTR induction, 2- and 5-year OS were 97% and 83%, while 2- and 5-year PFS were 83% and 63%, respectively. There were no treatment-related deaths. Survival outcomes did not significantly differ by consolidation strategy.
Conclusions:
In this first real-world analysis, MTR induction demonstrated high response rates, durable survival, and excellent tolerability, with comparable outcomes across consolidation approaches, supporting its use as an effective and tolerable first-line therapy for PCNSL.