Rituximab Plus CVP Improves Outcome in Follicular NHL

ATLANTA-Concomitant administration of rituximab (Rituxan) and chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) appears effective in patients with stage III-IV follicular non-Hodgkin's lymphoma (NHL), Philippe Solal-Cligny, MD, PhD, of the Jean Bernard Cancer Center, Le Mans, France, said at the 47th Annual Meeting of the American Society of Hematology (ASH abstract 350).

Dr. Solal-Cligny explained that "several randomized studies showed that a combination of rituximab plus chemotherapy significantly improved progression-free survival in patients with follicular lymphoma whose disease required initial treatment. However, there is no consensus on the optimal chemotherapy to give to these patients."

At ASH, Dr. Solal-Cligny and his colleagues presented updated efficacy results, with median follow-up of 42 months, of their phase III multicenter, international trial evaluating CVP plus rituximab as initial treatment for patients with CD20-positive, stage III-IV follicular NHL who had received no prior systemic therapy. They previously reported 30-month results in Blood (105:1417-1423, 2005).

Patients were randomized to receive CVP (n = 159) or rituximab plus CVP (R-CVP) (n = 162) for a total of four 3-week cycles, at which point patients were restaged. Those achieving at least a partial response were continued on the same regimen for four additional cycles. Almost half of all patients had a poor-prognosis Follicular Lymphoma International Prognostic Index (FLIPI) score of 3 to 5.

Study Results

The R-CVP regimen was significantly superior to CVP in terms of overall response rate (80.9% vs 56.6%, P < .0001) and proportion of patients achieving complete response (CR) or unconfirmed CR (40.7% vs 10%, P < .0001). The addition of rituximab also increased the durability of responses (median 38 months vs 13.5 months, P < .0001).

The median time to treatment failure was significantly longer with R-CVP vs CVP (27.0 vs 6.6 months, P < .0001), he reported, as were the median time to progression, relapse, or death (34 vs 14.5 months, P < .0001), and median disease-free survival (45 months vs 20.5 months, P = .0006). Although at 42 months median follow-up, the median overall survival had not been reached for either arm, the investigators observed a trend toward improved overall survival with the addition of rituximab (P = .0553).

A safety analysis showed an increased frequency in grade 3-4 adverse events in the combination arm: 34% of R-CVP patients had at least one grade 3-4 adverse event vs 19.5% with CVP. This was primarily due to an increased frequency of grade 3-4 neutropenia with R-CVP vs CVP (24% vs 14.5%). Dr. Solal-Cligny pointed out, however, that there was no increased incidence of febrile neutropenia, which was low in both arms.

He concluded that "with a longer follow-up of 3 years, the combination of rituximab with CVP continues to provide major benefits in patients with follicular lymphoma, including patients at high risk according to FLIPI, who constituted half of the study population."