CNS prophylaxis is (mostly) futile in DLBCL

Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is associated with a poor prognosis, with a median overall survival of approximately five months [1]. The risk for CNS disease has been estimated to be about 5% overall [2], but it is significantly higher in certain high-risk groups [3]. CNS prophylaxis is often administered to patients felt to be at high risk for CNS recurrence. Options for CNS prophylaxis include high-dose methotrexate (HD-MTX) and intrathecal (IT) chemotherapy with methotrexate and/or cytarabine. However, a number of recent retrospective analyses have called into question the efficacy of prophylaxis. Here, we aim to review the literature regarding CNS prophylaxis with HD-MTX or IT chemotherapy in DLBCL. Our review and discussion exclude Burkitt lymphoma and lymphoblastic leukemia/lymphoma, for which standard treatment protocols include CNS prophylaxis. We also exclude double and triple hit lymphoma (DHL, THL) as it is generally accepted that these patients are at a high risk of CNS relapse. Based on the results of several recent studies, we recommend consideration of IT chemotherapy instead of HD-MTX if prophylaxis is desired due to better tolerability. If HD-MTX is desired, it should be done after systemic therapy is completed to avoid treatment delays. We provide an algorithm to guide decision making. However, our review of the literature suggests that CNS prophylaxis by either means has no clear benefit.