Rituximab and Chlorambucil as Front-Line Treatment in Untreated Follicular Lymphoma: a Combination with a Durable Response and Low Toxicity Profile.

Follicular lymphoma (FL), one of the most common B-cell non-Hodgkin's lymphoma (NHL), is an indolent disease characterized by a continuous relapse pattern. In the last years the treatment have changed with the introduction of Rituximab, that in combination with chemotherapy prolongs the progression-free survival (PFS) and the overall survival (OS) of FL pts. We report here the results of a regimen containing Rituximab and Chlorambucil (Chl) in untreaed FL pts.

Since December 2001 48 pts (22 male and 26 female) with naive FL were treated in first-line with R-Chl. The schedule consisted of an induction phase with four weekly infusion of Rituximab at standard dose and 6 consecutive weeks of Chl at 6mg/mq/daily. Pts were restaged and in absence of disease progression received four cycles of consolidation with a monthly Rituximab infusion and 14 days of Chl each month.

Median age at diagnosis was 56 years (range 29-79). Ann Arbor stage was I-II in 13 pts and III-IV in 35 pts (73%); 15 pts had bulky disease and 14 pts presented an extranodal localization. B symptoms were present in 8 pts. Histological grading was available in 42 cases, and was 1 in 10 pts, 2 in 26 pts and 3 in 6 pts. FLIPI was evaluable in 46 pts, and was 0-1 in 25 pts (52%), 2 in 12 pts (25%), and >2 in 9 pts (18%). After the induction phase overall response rate (ORR) was 98% with 14 pts in complete remission (CR). After the consolidation phase 39 pts (81%) obtained a CR and eight (17%) a partial response (PR); the remaining patient had a stable disease and underwent high-dose chemotherapy and autologous transplantation. All pts but one concluded the planned treatment. The mean daily dose of Chl administered during the induction phase was 10 mg, while 8 mg in the prolonged treatment. Twenty-eight pts (58%) experienced a neutropenia during treatment, and Chl dose was reduced in 22 pts (46%); however, only 11 pts (23%) had a G3-4 neutropenia. The Chl was stopped only in a patient because of a persistent G3 neutropenia after the first consolidation cycle. After a median observation time of 42.5 months (range 7-94) nine pts relapsed (19%), with a median time to relapse of 20 months (range 7-66). Two pts died, one of disease progression and one of a pre-existing ovarian cancer.

Our results described a safe and feasible combination of immuno-chemotherapy in untreated FL pts. With respect to traditional treatments, our regimen shows a similar efficacy and a lower toxicity, that leads to an easier handling. The schedule including four monthly additional Rituximab administrations confirms the superiority of a prolonged exposure to Rituximab over the standard 4-weekly administrations. In conclusion, our data suggest that this combination may be considered as a valid first-line treatment of FL patients, especially in those not eligible for more aggressive chemotherapy regimens.

No relevant conflicts of interest to declare.