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

Unlabelled: Fludarabine-based regimens are highly effective as first-line therapy in patients with follicular lymphoma. Nevertheless, noticeable haematological toxicity has been reported using fludarabine-based regimens.

Aim: To analyse the combination of low-dose oral fludarabine and cyclophosphamide plus rituximab (FCR) as induction therapy, followed by rituximab as maintenance therapy.

Methods: We retrospectively analysed 73 patients diagnosed with low-grade follicular lymphoma treated with two different schemes: attenuated oral (AO) and standard intravenous (SIV) FCR.

Results: Overall response rate (ORR) was 95% (complete response rate, CRR 79.5%, partial response, PR 15.4%). CRR was 84.6% in AO vs. 61.9% in SIV (P = 0.058). 44.4% of patients underwent maintenance therapy. Grade 3-4 toxicities included neutropenia: 65.4%; anaemia: 39.7%; thrombocytopenia: five patients; infectious complications: six patients. There were no treatment-related deaths. 6.8% had a secondary malignancy. Progression-free survival (PFS) was 84.6% at 12 yr. The following variables influenced PFS in multivariate analysis: Hb < 12 g/dL [HR 4.7 (95% CI 1.18-18.6)], response after induction [HR 4.9 (95% CI 1.01-24)] for PR vs. CR and [HR 21.27 (95% CI 4.33-104)] for SD/DP vs. CR. OS was 83.1% at 12 yr. The following variables significantly influenced OS in multivariate analysis: not receiving rituximab as maintenance therapy (HR 10.7 (95% CI 1.4-82.5), increased levels of β2-microglobulin [HR 5.2 (95% CI 1.16-23.7)].

Conclusions: FCR allowed us to obtain a high response rate, which translated into promising progression free and overall survival with an acceptable and manageable toxicity profile, especially with the attenuated oral scheme.