ATLANTA—In patients undergoing treatment for follicular lymphoma, (FL) maintenance rituximab(Drug information on rituximab) (Rituxan) after a cyclophosphamide(Drug information on cyclophosphamide), vincristine, and prednisone(Drug information on prednisone) (CVP) regimen appears to confer a survival benefit, Sandra Horning, MD, professor of medicine, Stanford University, said at the 47th Annual Meeting of the American Society of Hematology (abstract 349).
Dr. Horning and her colleagues in the Eastern Cooperative Oncology Group (ECOG) hypothesized that in patients with indolent lymphoma, chemotherapy induction to maximal benefit followed by rituximab would improve progression-free survival (PFS). "Our initial study design was cyclophosphamide/fludarabine (CF) vs CVP with or without maintenance rituximab," Dr. Horning explained. "However, due to toxicity with the CF regimen, this arm was dropped and the study was revised and repowered in its current form."
Preliminary data from the E1496 study, presented at the American Society of Clinical Oncology meeting in 2004, indicated a superior PFS with maintenance rituximab. In the present analysis, investigators evaluated responses in patients with follicular lymphoma, as they are the dominant subtype in the trial and tend to demonstrate high response rates with rituximab. Of the 304 study patients, 237 had follicular lymphoma (stage III-IV) and were included in this analysis.
After receiving six to eight cycles of CVP (best response plus two additional cycles), patients with follicular lymphoma were randomized to receive maintenance rituximab (375 mg/m2 weekly for 4 weeks) (n = 120) or observation (n = 117). The maintenance regimen was initiated 4 weeks after CVP and repeated every 6 months for 2 years. Dr. Horning noted that the two arms were "overall well-balanced with two exceptions: [patients in] the observation arm tended to be younger, but also were more likely to have 5+ nodal sites."Follicular Lymphoma Results
Responses to CVP were not significantly different between arms. However, PFS from randomization to maintenance rituximab or observation was significantly longer in the rituximab arm (median PFS, 61 vs 15 months; P < .00001). Maintenance rituximab was associated with a hazard ratio (HR) of 0.40. At 3 years following randomization, the benefit conferred by maintenance rituximab was observed regardless of Follicular Lymphoma International Prognostic Index (FLIPI) score, tumor burden, or presence of residual disease.
Overall survival at 42 months was also significantly superior with maintenance rituximab (91% vs 75% with observation; HR 0.50; P = .03). A subgroup analysis found that maintenance rituximab provided significantly superior overall survival only in patients with a high tumor burden.
Dr. Horning pointed out that "the observation arm exceeded our expectation for overall survival, leading to caution in the use of historical controls in the current analyses of follicular lymphoma. This is consistent with other data that patients with follicular lymphoma are living longer. We anticipate that the majority of patients in this study who failed on the observation arm were able to receive rituximab as a part of their second-line treatment." She also noted that these are the first results that strongly suggest a survival benefit with maintenance rituximab in the initial treatment of follicular lymphoma.
