Rituximab Extended Schedule or Re-Treatment Trial for Low–Tumor Burden Follicular Lymphoma: Eastern Cooperative Oncology Group Protocol E4402

Abstract

Purpose In low–tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR. Patients and Methods Eligible patients with previously untreated low–tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL). Results A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms. Conclusion In low–tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy.

Primary duodenal follicular lymphoma with late disseminated nodal relapse responsive to rituximab monotherapy: A case report

“…The efficacy of this regimen in nodal FL was demonstrated in the RESORT trial. In low tumor burden nodal FL, a re-treatment strategy with rituximab 375 mg/m 2 for 4 weekly doses upon relapse provides disease control comparable to a rituximab maintenance strategy (23). The present case demonstrated the potential benefit of this protocol in GI-FL during initial treatment and nodal relapse.…”

Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/03

“…5 Also, at least two randomized studies have shown that the time to the next nonrituximab treatment is the same, whether rituximab is administered continually as maintenance or intermittently, at every progression. 11,13 The second strategy is probably more cost effective because it uses less than one half of the rituximab without apparently compromising survival.…”

Follicular lymphoma: evolving therapeutic strategies

“…54 After induction therapy with single-agent rituximab, patients with low-tumor-burden FL were randomized to receive maintenance rituximab until treatment failure or to be periodically re-treated with rituximab (re-treated with 4 weekly doses at each progression) until treatment failure. The trial revealed no difference in the time to treatment failure between the 2 dosing strategies.…”