Orlando—In an international, multicenter, randomized phase 3 trial of 462 patients with previously untreated asymptomatic, advanced stage follicular lymphoma, researchers concluded that rituximab significantly improved time to initiation of therapy as well as progression-free survival compared with watchful waiting. Kirit Ardeshna, MD, consultant hematologist at the University College London Hospitals and the trial’s lead author, presented the results during a plenary scientific session at the ASH meeting. The study was titled An Intergroup Randomized Trial of Rituximab Versus a Watch and Wait Strategy in Patients with Stage II, III, IV, Asymptomatic, Non-Bulky Follicular Lymphoma (Grades 1, 2 and 3a). Follicular non-Hodgkin lymphoma (f-NHL), a type of NHL, is incurable and is characterized by periods of relapse and remission. In 2010, an estimated 65,540 people in the United States were diagnosed with NHL; f-NHL accounted for approximately 15% to 20% of those cases. The standard approach to care for patients with asymptomatic, advanced stage f-NHL is watchful waiting, in which chemotherapy is delayed until the cancer progresses. On average, the watchful waiting approach defers chemotherapy 2.5 years. The approach results in improved quality of life for patients. In this trial, which enrolled 462 patients with previously untreated asymptomatic stage II, III, or IV f-NHL, the authors were interested in determining whether treatment with rituximab immediately after diagnosis would further delay the time until chemotherapy was needed. The study randomized patients in 3 treatment arms between September 2004 and May 2009: 186 patients underwent a watchful waiting approach; 84 patients received 375 mg/m2 of rituximab once per week for 4 weeks; and 192 patients received 375 mg/m2 of rituximab once per week for 4 weeks followed by maintenance therapy with rituximab every 2 months for 2 years. Originally, the study was designed to show an improvement for 18 months in the median time to the start of therapy in each of the rituximab arms (from 30 to 48 months). The authors wanted to enroll 600 patients to identify 230 who required chemotherapy or radiotherapy treatment. However, 3 years into the trial, after the efficacy of rituximab as a maintenance therapy became apparent, the researchers discontinued the second arm. The 2-arm comparison included 360 patients, and the authors estimated they would require 192 patients to show the 18-month improvement. The researchers found that immediately using rituximab monotherapy as induction followed by maintenance therapy decreased the risk of needing additional therapy by 80% (hazard ratio [HR], 0.20; 95% confidence interval [CI], 0.15-0.29; P<.001) compared with the watchful waiting approach. In addition, the rituximab arm showed a decreased risk of disease worsening by 79% (HR, 0.21; 95% CI, 0.15-0.29; P<.001). Patients managed under the watchful waiting approach had a median time to initiation of new therapy (chemotherapy or radiotherapy) of 34 months and a median progression-free survival of 23 months. The median of both measures was significantly higher (P<.0001) in the rituximab group and had not been reached after 4 years. As of March 2010, when the data monitoring committee recommended full analysis of the data, 20 patients were still undergoing rituximab maintenance. The authors found 45 serious adverse events (SAEs), and SAEs in patients treated with rituximab included infection (4%), allergy (3%), neutropenia (3%), and neutropenic sepsis (1%). Dr. Ardeshna said it was unclear whether overall survival will be improved using rituximab. He mentioned researchers needed to determine the impact of prior rituximab on response to the first new treatment, the response duration of the first new treatment, and the time to initiation for the second new treatment.