Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma

Abstract

Anti-CD20-containing chemotherapy regimens have become the standard of care for patients with follicular lymphoma needing cytotoxic therapy. Four randomized trials demonstrated a clinical benefit for patients treated with rituximab. However, no long-term follow up (i.e. > 5 years) of these trials is yet available. Between May 2000 and May 2002, 358 newly diagnosed patients with high tumor burden follicular lymphoma were randomized to receive cyclophosphamide, adriamycin, etoposide and prednisolone plus interferon-α2a or a similar chemotherapy-based regimen plus rituximab, and outcome was up-dated. With a median follow up of 8.3 years, addition of rituximab remained significantly associated with prolonged event-free survival (primary end point) (P=0.0004) with a trend towards a benefit for overall survival (P=0.076). The Follicular Lymphoma International Prognostic Index score was strongly associated with outcome for both event-free and overall survival in univariate analysis and its prognostic value remained highly significant after adjusting for other significant covariates in multivariate models (P<0.0001 and P=0.001, respectively). Considering long-term toxicity, the addition of rituximab in the first-line setting was confirmed as safe with regards to development of secondary malignancies. Long-term follow up of patients with follicular lymphoma treated in the FL2000 study confirms the sustained clinical benefit of rituximab without long-term toxicity.

Figure 1.

Trial profile of the FL2000 study.

Figure 2.

(A) Kaplan-Meier (KM) estimates of event-free survival (EFS) according to treatment arm (CHVP+I vs. R-CHVP+I). (B) Response duration (RD) according to treatment arm. (C) Overall survival (OS) according to treatment arm. (D) KM estimates of EFS according to FLIPI category. (E) OS according to FLIPI category. FLIPI, Follicular Lymphoma International Prognostic Index. CHVP: cyclophosphamide-adriamycin-vincristine-prednisone; I: alpha-interferon; R: rituximab.

Figure 3.

Forest plot representation of the effect of the addition of rituximab on event-free survival according to baseline categories. ECOG, Eastern Cooperative Oncology Group; LDH: lactate dehydrogenase; UNL: upper normal limit; FLIPI: Follicular Lymphoma International Prognostic Index; CHVP: cyclophosphamide-adriamycin-vincristine-prednisone; I: alpha-interferon; R: rituximab.

Figure 4.

Biweight Kernel smoothed estimates of event hazard rates. (A) For the whole cohort. (B) According to treatment arm. Hazard rate functions represent the rate of events per year.