Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402.

The rituximab extended schedule or retreatment trial (RESORT; E4402) was a phase 3 randomized prospective trial comparing maintenance rituximab (MR) versus a retreatment (RR) dosing strategy in asymptomatic, low tumour burden indolent lymphoma. A planned exploratory sub-study compared the two strategies for small lymphocytic (SLL) and marginal zone lymphomas (MZL). Patients responding to rituximab weekly x 4 were randomized to MR (single dose rituximab every 3months until treatment failure) or RR (rituximab weekly x 4) at the time of each progression until treatment failure. The primary endpoint was time to treatment failure (TTTF). Patients with SLL (n=57), MZL (n=71) and unclassifiable small B-cell lymphoma (n=3) received induction rituximab. The overall response rate (ORR) was 40% [95% confidence interval (CI) 31-49%; SLL ORR 228%; MZL ORR 521%]; all 52 responders were randomized. At a median of 43years from randomization, treatment failure occurred in 18/23 RR and 15/29 MR. The median TTTF was 14years for RR and 48years for MR (P=0012); median time to first cytotoxic therapy was 63years for RR and not reached for MR (P=00002). Survival did not differ (P=072). In low tumour burden SLL and MZL patients responding to rituximab induction, MR significantly improved TTTF as compared with RR.