Fludarabine, cyclophosphamide and rituximab in patients with advanced untreated indolent B-cell non-follicular lymphomas : final result of phase two study of Fondazione Italiana Linfomi (FIL)

Indolent non-follicular non-Hodgkin lymphomas (INFL) are a heterogeneous subset of diseases whose treatment has not been clearly defined. To this end, we evaluated the efficacy and safety of first-line therapy with rituximab, fludarabine and cyclophosphamide (FCR) followed by rituximab maintenance in patients with advanced INFL. This single arm, multicenter, open-label phase II study evaluated the activity of FCR induction immunochemotherapy (rituximab: 375 mg/m2 i.v. on Day 1 of each cycle and on Days 1 and 14 of cycles 4 and 5; fludarabine: 25 mg/m2 i.v. on Days 2-4; cyclophosphamide: 250 mg/m2 i.v. on Days 2-4), every 28 days for six cycles followed by a maintenance phase with four infusions of rituximab (375 mg/m2 i.v. on Day 1) every two months for responder patients. Forty-seven previously-untreated patients with advanced INFL were enrolled in the study. Among 46 evaluable patients (28 males, median age 59 years), 19 were diagnosed with lymphoplasmacytic lymphoma (LPC), 21 with small lymphocytic lymphoma (SLL) and 6 with nodal marginal zone lymphoma (MZL). The final overall response rate was 78.3% with 65.3% complete remission (CR/CRu) and 13% partial response. After a median follow-up of 40.9 months, FFS and PFS were 90.1%, and OS was 97.4%. The main toxicity was hematological; related grade III-IV neutropenia was observed in 55.3% of patients. FCR induction therapy followed by a short maintenance phase with rituximab is a highly effective regimen with acceptable toxicity for patients with advanced untreated INFL.