Phase 2 trial of high-dose rituximab with high-dose cytarabine mobilization therapy and high-dose thiotepa, busulfan, and cyclophosphamide autologous stem cell transplantation in patients with central nervous system involvement by non-Hodgkin lymphoma.

BACKGROUNDHigh-dose thiotepa, busulfan, and cyclophosphamide (TBC) with autologous stem cell transplantation (ASCT) has been used in patients with central nervous system (CNS) involvement by non-Hodgkin lymphoma (NHL). Despite limited penetration into the CNS, rituximab is active in primary CNS NHL. Therefore, high-dose rituximab was combined with TBC for ASCT in patients with CNS NHL. METHODSA single-arm phase 2 trial using high-dose rituximab with cytarabine for stem cell mobilization followed by high-dose rituximab combined with thiotepa, busulfan, and cyclophosphamide (R-TBC) for ASCT was conducted. Doses of rituximab at 1000 mg/m(2) were given on days 1 and 8 of mobilization and on days -9 and -2 of TBC. The primary endpoint was efficacy. RESULTSThirty patients were enrolled. Eighteen patients had primary CNS NHL (12 with complete remission (CR)/first partial remission (PR1) and 6 with CR/PR2), and 12 patients had secondary CNS lymphoma (5 with CR/PR1 and 7 with CR/PR2 or beyond). All patients were in partial or complete remission. Twenty-nine patients proceeded to R-TBC ASCT. Two patients developed significant neurotoxicity. The 100-day nonrelapse mortality rate was 0%, and 1 patient died because of nonrelapse causes 5 months after ASCT. For all patients, at a median follow-up of 24 months (range, 12-40 months), the estimated 2-year progression-free survival rate was 81% (95% confidence interval, 59%-92%), and the 2-year overall survival rate was 93% (95% confidence interval, 76%-98%). There were no relapses or deaths among the 18 patients with primary CNS lymphoma. CONCLUSIONSFor patients with CNS involvement by B-cell NHL and especially for patients with primary CNS NHL, R-TBC ASCT shows encouraging activity and merits further study. Cancer 2015;121:226-33. (c) 2014 American Cancer Society. Using high-dose systemic rituximab may allow higher concentrations to penetrate the central nervous system. This article presents a phase 2 trial combining high-dose rituximab with standard autologous stem cell transplantation and shows compelling results in patients with central nervous system involvement by non-Hodgkin lymphoma.