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. Issue 2 (9th September 2014) - Chen, Yi‐Bin
Abstract BACKGROUND High‐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. METHODS A 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/m2 were given on days 1 and 8 of mobilization and on days −9 and −2 of TBC. The primary endpoint was efficacy. RESULTS Thirty 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. CONCLUSIONS For 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. © 2014 American Cancer Society.