Prolonged disease-free survival and overall survival with CVP alternating with fludarabine in advanced follicular lymphoma

Cyclophosphamide and fludarabine are highly active in treating follicular lymphoma (FL). However, many cyclophosphamide and fludarabine combination regimens, although highly effective, exhibited severe infectious toxicities including toxic death [1-7]. We designed a novel sequential regimen consisting of CVP (cyclophosphamide 400 mg/m(2) PO d1-5, vincristine 2 mg d1, prednisone 100 mg/m(2) d1-5) alternating with fludarabine (25 mg/m(2) IV d1-5) as induction chemotherapy for idiotype vaccination, with a goal of obtaining a higher quality of tumor debulking before vaccination. Herein, we report the safety and efficacy of this regimen. Thirty-four consecutive untreated patients with FL received this regimen. Toxicities were modest with no severe infections or toxic deaths. Complete response/unconfirmed complete response (CR/CRu) was achieved in 18 patients (53%) and PR in 38%. At a median follow-up of 12 years, overall survival (OS), event-free survival (EFS), time to progression (TTP), and disease free survival (DFS) were 85, 37, 38, and 70%, respectively. Among a cohort of historical controls with similar characteristics receiving CVP, the CR rate was 34%, 12-year OS, EFS, TTP, and DFS were 64, 20, 21, and 37%, respectively. Thus, CVP/F exhibited favorable safety profile while maintaining the excellent efficacy of combining cyclophosphamide and fludarabine and warrants further evaluation in combination with rituximab.