Background: In the majority of patients with follicular lymphoma (FL), chemotherapy results in initial high rates of remission, but the disease relapses in many patients. The response rates decrease in patients with relapsed disease, as does the response duration. A high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) strategy has been shown to improve outcomes in patients with FL recurrence. Although the role of rituximab maintenance in relapsed FL in the first-line and salvage settings has been established, the role of second-line rituximab maintenance after HDC-ASCT has not been investigated.
Design: This is the first randomized prospective study to compare the safety and efficacy of rituximab use as an in vivo purging agent before collecting the stem-cell product and/or as post-ASCT maintenance therapy. Between October 1999 and April 2006, 280 patients with relapsed FL who achieved complete remission (CR) or very good partial remission (VGPR) were enrolled in the European Group for Blood and Marrow Transplantation Lymphoma 1 trial, which was conducted in 87 centers in 13 countries. (The trial was stopped early because of slow recruitment.) Patients were randomized in a 2 × 2 factorial design to rituximab purging (N = 141) versus no rituximab purging (N = 139), and to rituximab maintenance (N = 138) versus no rituximab maintenance (N = 142). The randomization was stratified by CR versus VGPR and by number of remissions. The primary end point was progression-free survival (PFS).
Results: Various chemotherapy regimens were used to reinduce remission in these patients. After reinduction chemotherapy, 84 (30%) patients had CR and 196 (70%) patients had VGPR. Overall, 80 (29%) patients withdrew from the trial, with similar withdrawal rates between the groups. A total of 6 patients withdrew after ASCT; 57 patients did not mobilize; 3 patients were not eligible; 14 patients were noncompliant; 5 withdrew because of a severe adverse event; and 1 withdrew for other reasons. In vivo purging with rituximab had no effect on PFS at 10 years: the PFS rate was 48.6% (95% confidence interval [CI], 39.6-56.9) with rituximab purging versus 42.0% (95% CI, 33.5-50.4) without purging. By contrast, ri- tuximab maintenance had a significant impact on PFS: at 10 years, the PFS rate for rituximab maintenance was 54% (95% CI, 45.0-62.2) versus only 37% (95% CI, 28.6-45.3) without rituximab maintenance. No impact on overall survival (OS) was seen in any of the groups. This study shows for the first time the benefit and safety of rituximab maintenance for up to 8 months after HDC-ASCT in prolonging patients’ PFS.
Takeaway: This study shows that rituximab maintenance after HDC-ASCT and not rituximab purging before HDC-ASCT improves PFS. The median PFS was almost 7.5 years for patients receiving maintenance rituximab, far exceeding the PFS (3.7 years) seen in patients receiving maintenance after R-CHOP reinduction therapy. It is important to note that the PFS curve plateaued at 7.5 years, suggesting that HDC-ASCT can control the disease in a subgroup of patients. Although OS was not improved, Pettengell and colleagues stated that many patients who relapsed in the nonmaintenance arm were crossed over to rituximab maintenance. The 10-year OS rate is impressive, with 74% of patients alive. Patients receiving maintenance rituximab tolerated treatment well; only 4 infusion-related reactions were reported.
Pettengell R, Schmitz N, Gisselbrecht C, et al. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the lymphoma working party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2013;31:1624-1630.