Frontline treatment of follicular lymphoma with fludarabine, cyclophosphamide, and rituximab followed by rituximab maintenance: toxicities overcome its high antilymphoma effect. Results from a Spanish Cooperative Trial (LNHF-03)

Abstract

We assessed the efficacy of fludarabine, cyclophosphamide, and rituximab in combination (FCR) as frontline treatment in patients with follicular lymphoma (FL) followed by rituximab maintenance. Seventy-five untreated patients with FL received FCR followed by maintenance with rituximab 375 mg/m(2) weekly during 4 weeks and every 6 months for 2 years. The overall response rate was 100%, with 89% complete remission (CR) and 11% partial remission (PR). Molecular remission was observed in all but one patient. Only eight patients completed all therapy planned. With a median follow-up of 47 months, the 5-year overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) were 77%, 93%, and 72%, respectively. Age below 60 and low Follicular Lymphoma International Prognostic Index (FLIPI) correlated with a better EFS. Ten patients died due to toxic complications. The FCR regimen is highly effective in untreated patients with FL, with 89% CR, including molecular responses, and a low progression rate. However, the high incidence of treatment-related mortality makes this regimen unsafe and it cannot be recommended as an upfront therapy in FL.

High ten‐year remission rates following rituximab, fludarabine, mitoxantrone and dexamethasone (R‐FND) with interferon maintenance in indolent lymphoma: Results of a randomized Study

“…With mature follow‐up, our findings suggest that depth of response may predict duration of response. Similarly, other prospective studies examining a fludarabine‐based frontline regimen in indolent lymphoma have demonstrated high complete response rates which translated into prolonged response duration (Zinzani et al , ; Montoto et al , ; Tomas et al , ; Vitolo et al , ). A retrospective analysis of 536 patients with FL enrolled in the Groupe d'Etude des Lymphomes de l'Altude (GELA) GELF86 studies with 14·9 years of follow‐up reported that achieving a CR with first‐line therapy was associated with superior OS (Bachy et al , ).…”

Fludarabine, cyclophosphamide and rituximab as first‐line treatment in patients with newly diagnosed follicular lymphoma

“…By contrast, Tomás et al . , evaluated the efficacy of six cycles of FCR (fludarabine 25 mg/m 2 IV × 3, cyclophosphamide 1 g/m 2 × 1, rituximab 375 mg/m 2 × 1) followed by rituximab maintenance and reported a CR rate of 78% after induction and 92% after maintenance, but an unacceptably high rate of haematological toxicities (69% grade 3–4 neutropenia with a significant number of opportunistic infections). This led to premature termination of the trial.…”

Early initial therapy of advanced follicular lymphoma: the need for vigilance

“…In this issue of Leukemia and Lymphoma, Tomás et al have investigated the use of a fludarabine-based, rituximab-containing induction regimen followed by rituximab maintenance therapy in previously untreated patients with advanced follicular lymphoma [9]. Seventy-five patients were entered onto a prospective phase II study in which the planned treatment was six cycles of fludarabine, cyclophosphamide, and rituximab, followed by maintenance rituximab given at 6-month intervals for a total of 2 years of therapy.…”