Long-Term Followup of Patients with Follicular Lymphoma (FL) Treated with Two Years of Maintenance Rituximab: Response to Rituximab Retreatment at Progression.

Background: Maintenance treatment with rituximab prolongs progression-free survival (PFS) in patients with FL when administered following single agent rituximab, chemotherapy, or rituximab/chemotherapy combinations. However, the possible induction of lymphoma resistance by prolonged rituximab treatment has been a cause for concern. To address this issue, we obtained long-term followup on patients who had received 2 years of maintenance rituximab and had objective response or stable disease when treatment was discontinued. With a median followup of 7 years, we evaluated the subsequent course of these patients, with particular attention to:

1. treatment administered at relapse,

2. sensitivity to retreatment with rituximab at progression, and

3. survival.

Methods: Between March 1998 and August 2002, we treated a total of 106 patients in 2 sequential studies with single-agent rituximab, followed by rituximab maintenance therapy (repeated 4-week courses every 6 months for 2 years). In both studies (

Results: Nineteen of 58 patients (33%; 18% of all 106 patients treated) remain in continuous remission after a median followup of 7 years (range 4–8 years). Thirty-five patients progressed, while 4 patients died of intercurrent illnesses while in remission. Of the 35 patients who progressed, 24 patients received single-agent rituximab as the next therapy, while 2 patients received rituximab in combination with chemotherapy. Eight of 24 patients (33%) had objective responses to single-agent rituximab (CR 5, PR 3), 14 patients (58%) had stable disease, and 2 patients progressed. Six of the responding patients again received maintenance rituximab. Median PFS in the 22 responding/stable patients was 47 months (95% CI = 39–52 months) with 27% of patients progression-free at 5 years. Both patients receiving rituximab plus chemotherapy had complete remissions (durations 33, 64 months). Transformation to a more aggressive histology was not documented in any patient. The median survival of all 35 relapsing patients, measured from the time of relapse, is 63 months, (95% CI = 40-N.R.).

Conclusions: The majority of patients who relapse after 2 years of maintenance rituximab therapy remain sensitive to rituximab. Retreatment with rituximab, either as a single agent or in combination with chemotherapy, is a reasonable therapeutic option at the time of progression. Further investigation of more prolonged rituximab maintenance schedules is indicated.