Outcomes at a single institution with MTR induction and consolidation in the management of primary CNS lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare form of aggressive non-Hodgkin lymphoma. Given its infrequency, there are few randomized trials to guide induction and consolidation strategies, with no consensus on optimal treatment. Most centers will offer high-dose methotrexate-based induction chemotherapy followed by either autologous stem cell transplant, whole-brain radiation, or prolonged chemotherapy. The preferred strategy at our institution has been 6 doses of methotrexate, temozolomide, and rituximab (MTR) induction with methotrexate on day 15 until complete response for induction followed by 6 monthly cycles of MTR. We conducted a retrospective analysis of patients diagnosed with PCNSL at the University of Pennsylvania from 1 April 2008 to 1 October 2024, identifying 153 patients who received this regimen. With a follow-up of 63 months, the median overall survival (OS) in the entire cohort was 65 months, with a median relapse-free survival (RFS) of 36 months. In the cohort of patients who were able to complete 6 months of MTR induction and proceed with MTR consolidation, median OS and RFS were 143 and 122 months, respectively. Although 13% of patients discontinued therapy because of toxicity, there was no treatment-related mortality. These results indicate that prolonged MTR is a safe treatment option and an alternative to intensified consolidation strategies. Further randomized studies are necessary to determine the optimal treatment strategy in newly diagnosed PCNSL.