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Maintenance therapy for central nervous system lymphoma with rituximab

Primary central nervous system lymphoma (PCNSL) is a rare type of malignant non-Hodgkin lymphoma (NHL) that is confined to the brain, eyes, and cerebrospinal fluid. Response rates of 490% have been reported following high-dose methotrexate regimens for newly diagnosed PCNSL with a median survival of up to 5 years [1,2]. However, at least 50% of the patients relapse, usually within 2 years of initial diagnosis. At relapse many patients achieve a second remission; however, the duration of a second remission is typically short, averaging 6–10 months. Parenchymal brain relapse following systemic NHL is often treated with methotrexate or whole brain radiotherapy, but prognosis is generally poor with survivals in the range of 2–5 months [3,4]. The high rate of recurrence after successful treatment of central nervous system (CNS) lymphoma highlights the need for consolidation therapy to maintain disease control. The most widely used consolidation approaches include whole brain radiotherapy and myeloablative chemotherapy. However, whole brain radiotherapy carries a risk of significant neurocognitive morbidity particularly in older patients. Myeloablative chemotherapy has been shown to be ineffective for patients with systemic NHL who have CNS metastases although most patients studied in this context have had leptomeningeal lymphoma [5]. Although there are promising preliminary data for myeloablative chemotherapy in PCNSL, the benefit has been limited to young patients with good prognostic features which preclude this approach for the majority of patients. The concept of maintenance therapy as consolidation was originally developed for patients with acute lymphoblastic leukemia to maintain remission. More recently, this strategy has been used for patients with indolent lymphoma; however, in this patient population the goal of maintenance rituximab has been to minimize or control residual tumor burden [6–9]. The CNS lymphoma is an aggressive B-cell lymphoma; therefore, we hypothesized that maintenance therapy may be effective in patients with PCNSL at high risk for relapse after they have achieved a complete response (CR) with standard treatments. As this strategy has minimal morbidity, we used maintenance rituximab for a series of patients with CNS lymphoma who were at high risk for relapse and/or unable to receive alternate consolidation treatment. Nine patients with CD20þ CNS lymphoma were treated with maintenance rituximab between November 2004 and March 2009. Maintenance rituximab was defined as delivery of regularly scheduled rituximab following a radiographic CR after treatment for CNS lymphoma. Hospital charts, radiology and pathology reports, and clinical notes were reviewed. Permission for this retrospective study was granted by the Institutional Review Board at Memorial Sloan-Kettering Cancer Center. Disease-free survival was calculated from the date of the MRI scan documenting a CR after therapy for CNS lymphoma and immediately prior to initiation of maintenance rituximab until documented progression or last follow-up. The OS was calculated from the date of this MRI scan until the date of death or last follow-up. The date of original tissue diagnosis was used as the date of diagnosis. The Kaplan–Meier product limit method was used to generate survival