The Addition of Rituximab to CVP (Bagley) + Interferon-α as Induction Regimen, Significantly Increases Complete Remission Rates and Progression Free Survival In Intermediate-High Risk Follicular Lymphoma Patients (LNH-pro vs. LNH-pro-05 trial)

Survival of Follicular Lymphoma patients has significantly increased with the introduction of immunomodulatory agents, such as Interferon (IFN) and Rituximab (R). Until 2002 our Follicular Lymphoma patients were included in a trial and received induction therapy with CVP + Interferon (LNH-pro, JCO 16; 1538–1546). Since 2006, Rituximab is being added to the same induction regimen (LNH-pro-05, EHA 09). Herein we communicate the comparative results between these two trials in Intermediate-High risk Follicular Lymphoma patients.

To compare toxicity and efficacy in terms of complete remission (CR) and Progression Free Survival (PFS) between both trials in Intermediate-High risk Follicular Lymphoma patients.

Patients in the LNH-pro trial (1990-2006) received CVP (CY 400mg/m2 p.o D1-5, VCR 1.4mg/m2 iv D1, PRD 100mg/m2 po D1-5) + IFN (3MU/m2 sc, 3 times/wk, for 12 wks). When it became available, G-CSF support was permited. In the LNH-pro-05 trial (2006-ongoing), Rituximab (R: 375mg/m2 iv D1) was added to the same induction regimen. All patients received 8 cycles as per protocol, with G-CSF support and Pn. jiroveci prophilaxis. In both studies, complete re-assessment was performed after cycle 4, at the end of induction therapy, every 4 months for the first 2 years and every 6 months thereafter.

We analysed data from 74 and 36 FL patients with FLIPI≥2, included in the LNH-pro and LNH-pro-05 trials, respectively. Patients' characteristics are shown in table 1. No significant differences were found between groups, except for a higher incidence of elevated B2-microglobulin in patients treated with CVP+IFN and higher Bulky disease (>7cm) among patients with R+CVP+IFN. Median number number of cycles were 6 and 8, respectively. Response: Seventy one patients (96%) in the LNH-pro Trial (CVP+IFN) were evaluable for response. Overall Response (OR) rate was 87%, with 68% Complete Remission (CR) and 19% Partial Remission (PR) (9% non-responders).

In the LNH-pro-05 Trial (R+CVP+IFN), 36 patients (92%) and 33 patients (83%) were evaluable for response after 4^th and 8^th cycle. At cycle 4, all assesed patients achieved remission (15% PRs and 85% CR+uCR), while after the 8^th cycle 100% of patients are in CR or uCR. Toxicity. Main hematologic grade 3–4 toxicity was neutropenia, 33% for CVP+IFN and 28% for R+CVP+IFN, with 12% and 6% of infections, respectively. Other non-hematologic toxicities were infrequent and mild (5% and 10% in each group). Eight percent of patients in the LNH-pro trial withdrew treatment due to toxicity. At the moment, none of the patients in the LNH-pro-05 trial have experienced an unacceptable toxicity.

Survival. Median follow-up was 7.7 years for CVP+IFN and 2 years for R+CVP+IFN. A significant increase of PFS was seen among patients who received R (66% vs. 86%, at 3 years, P 0.05). There is also a trend to a longer overall survival in patients treated with R+CVP+IFN (P 0.07).

The addition of Rituximab to CVP+IFN induction regimen in Intermediate-High risk Follicular Lympoma patients, significantly increases complete remission rates (88% to 100%) and progression free survival (86%, at 3 years), with a low toxicity profile.

No relevant conflicts of interest to declare.