• Prolonged MTR for induction and consolidation is a safe alternative treatment strategy for the management of PCNSL.

Primary CNS 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 April 1, 2008 – October 1, 2024 identifying 153 patients who received this regimen. With a follow up of 63 months, the median overall survival (OS) in the entire cohort 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. While 13% of patients discontinued therapy due to 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.

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Data Sharing Statement:

The data supporting the findings of this study are available upon reasonable request from the corresponding author

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