High clinical and molecular response rates with fludarabine, cyclophosphamide and mitoxantrone in previously untreated patients with advanced stage follicular lymphoma.

Background: Purine analogs have demonstrated significant activity in patients with follicular lymphoma. The aim of this study was to analyze the efficacy and toxicity of a fludarabine combination as first-line treatment in patients with advanced-stage disease.

Design And Methods: This is a phase II trial including 120 patients (< or =65 years) treated with 6 cycles of fludarabine, cyclophosphamide and mitoxantrone (FCM). Molecular response was assessed by q-PCR in peripheral blood.

Results: Of 119 patients with an assessable response, complete response was achieved in 99 (83%) partial response in 13 (11%) and 7 (6%) did not respond. After treatment, 37 out of 46 (81%) patients achieved molecular response. After a median follow-up of 3.9 years, 32 patients have relapsed. The 5-year progression-free survival was 58% (95% confidence interval: 47-69). Variables associated with a shorter progression-free survival were a poor performance status (ECOG> or =2), > or =2 extranodal sites and high beta2-microglobulin. Sixteen episodes of grade 3-4 infections were observed. Two patients died during therapy (of progressive multifocal leukoencephalopathy and bronchoaspiration respectively). No late toxicity has been observed. Twelve patients died during follow-up (9 after relapse, 2 during chemotherapy, 1 in complete remission after surgery for meningioma). The overall survival at 5 years was 89%. ECOG > or =2 and high beta2-microglobulin were associated with a shorter survival.

Conclusions: FCM results in high complete and molecular response rates, with prolonged response duration in younger patients with advanced-stage follicular lymphoma. The combination of FCM with rituximab as front-line treatment warrants further investigation.