Molecular Remission after Induction Chemo- Immunotherapy and Rituximab Maintenance in Previously Untreated Follicular Lymphoma.

Rituximab in combination with chemotherapy achieves the best result in follicular lymphoma.

Only limited data are available with rituximab as maintenance in first line setting.

We conducted a prospective multicenter trial in patients with previously untreated follicular lymphoma stage III or IV, which required therapy. Primary endpoint was conversion of BCL2/IgH PCR positivity to negativity. BCL2/IgH was centrally measured by a two-step qualitative PCR in peripheral blood and bone marrow before and after induction therapy, after maintenance treatment and yearly thereafter. Induction therapy (R-FM) consisted of 6 cycles of rituximab 375 mg/qm i.v. day 1, mitoxantrone 10 mg/qm i.v. day 1, fludarabine 25 mg/qm i.v. days 2-4 recyling every 28 days for 6 cycles. I.v. Fludarabine could be substituted by 30 mg/qm p.o. days 2-4 at the discretion of the investigator. Patients not progressing during induction therapy received maintenance rituximab 375 mg/qm every 8 weeks for 12 doses.

Twenty-seven patients were entered in the study. Median age was 55 years, (range 32-73 years). Rituximab serum concentrations were measured before and after rituximab infusion during induction and maintenance. Mean rituximab trough serum concentrations before maintenance cylce 1, 2, 4, and 6 were 46, 32, 38, and 37 ng/ml, respectively. Induction R-FM resulted in 16 (59.3%) complete (CR) and 11 (40.7%) partial remissions (PR). During maintenance rituximab 3 patients with PR converted to CR and another 2 progressed. After a median observation period of 33 months 3 year event free and overall survival are 79% (95% CI: .5322; .9168) and 86% (95% CI: .6355; .9544), respectively. In all 19 patients in whom samples were available after the end of R-FM induction BCL2/IgH was negative. During rituximab maintenance therapy 2 of 12 samples became positive for BCL2/IgH. One at relapse on maintenance and the other after completion of maintenance still in clinical CR.

With R-FM a high rate of stable remissions can be achieved. Rituximab through serum concentrations were within an effective range. All analyzed BCL2/IgH samples where negative already after induction with R-FM, even though the quality of the remission was improving in some patients during maintenance treatment. The additional effect of rituximab maintenance in first remission remains unclear. The results of randomized trials will elucidate the role of rituximab maintenance treatment in first remission of follicular lymphoma.

Fridrik:Bayer: Honoraria, Speakers Bureau; Roche Austria: Honoraria, Research Funding, Speakers Bureau. Off Label Use: Rituximab maintenance in first remission of follicular lymphoma. Greil:Roche: Honoraria, Research Funding. Hopfinger:Roche: Speakers Bureau; Mundipharm: Speakers Bureau. Jaeger:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel grants.