Dose-modified methotrexate, rituximab, and temozolomide induction achieves durable remissions in PCNSL

High-dose methotrexate (HD-MTX)-based regimens, often combined with rituximab and alkylating agents, remain the induction backbone for primary central nervous system diffuse large B-cell lymphoma (PCNSL). We report outcomes of a less-intensive regimen of HD-MTX, rituximab, and temozolomide. In this single-center retrospective analysis, patients with newly diagnosed PCNSL received HD-MTX 3.5 g/m2 every 21 days for up to 8 doses, rituximab 500 mg/m2 every 21 days for 6 doses, and temozolomide 150 mg/m2 for 5 days every 42 days for up to 4 months. Forty patients (17 men, 23 women) were treated. Median age at diagnosis was 66 years (range, 28-89), and median Karnofsky performance status was 80 (range, 60-90). Thirty-two patients (80%) received at least 6 HD-MTX cycles; 3 (8%) discontinued HD-MTX due to nephrotoxicity. At the end of induction, the overall response rate was 95% and the complete response rate was 77%. With a median follow-up of 33.9 months, 2-year progression-free survival (PFS) and overall survival (OS) were 73% and 78%, respectively. In patients aged ≥70 years (n = 15), 2-year PFS and OS were both 72%. Two-year PFS and OS were 82% and 94%, respectively, after consolidation with high-dose chemotherapy and autologous stem cell transplantation (n = 17), and 89% and 86% with maintenance therapy (n = 9). This less-intensive regimen achieved favorable complete response rates, survival, and tolerability in patients with newly diagnosed PCNSL, including in patients aged ≥70 years, a population historically underserved by available treatments.