Rituximab Maintenance Delays Need for Subsequent Treatment vs Watchful Waiting in Asymptomatic Nonbulky Follicular Lymphoma
In an open-label phase III trial reported by Ardeshna et al in The Lancet Oncology, rituximab (Rituxan) induction plus maintenance was found to delay the need for subsequent therapy and improve elements of quality of life vs watchful waiting in patients with advanced asymptomatic nonbulky follicular lymphoma.
Study Details
In the trial, 463 asymptomatic patients aged ≥ 18 years with low-tumor-burden follicular lymphoma (grades 1, 2, and 3a) at 118 centers in the UK, Australia, New Zealand, Turkey, and Poland were randomly assigned between October 2004 and March 2009 to receive watchful waiting (n = 187), rituximab at 375 mg/m2 weekly for 4 weeks (rituximab induction, n = 84), or rituximab induction followed by maintenance consisting of 12 infusions given at 2-month intervals for 2 years (maintenance rituximab, n = 192).
After randomization of 84 patients to the induction group, the treatment arm was closed due to low recruitment and because other studies had shown a benefit for rituximab maintenance vs watchful waiting after induction with rituximab with or without chemotherapy; only one such study had used rituximab monotherapy. The current study was amended to a two-arm trial.
The primary endpoints were time to start of new treatment with systemic chemotherapy or radiotherapy and quality of life at month 7 (6 months after completion of rituximab induction). Quality of life was assessed by the Functional Assessment of Cancer Therapy–General (FACT-G), Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale–Revised, and questions from the Illness Coping Style, Illness Impact Bank, and Mental Adjustment to Cancer Scale, together with four additional lymphoma-related questions.
The rituximab maintenance group and watchful waiting group were generally balanced for age (median, 60 years in both), sex (48% and 58% women), Eastern Cooperative Oncology Group performance status (0 in 91% and 90%), disease grade (1 in 48% in both, 2 in 42% and 43%, 3a in 10% in both), disease stage (II in 21% and 19%, III in 38% and 36%, IV in 41% and 45%), normal lactate dehydrogenase concentration (95% in both), Follicular Lymphoma International Prognostic Index score (eg, 1 in 24% and 28%, 2 in 44% and 36%, 3 in 20% and 27%), and β2 microglobulin ≤ 2.4 mg/L (74% and 78%).
Significant Delay in Need for New Treatment
Median follow-up was 46 months in the two-arm trial and 50 months in the three-arm trial. At 3 years, 88% of the rituximab maintenance group vs 46% of the watchful waiting group had not needed further treatment (hazard ratio [HR] = 0.21, P < .0001). No treatment was needed by 78% of patients in the rituximab induction group, which was significantly better than the rate in the watchful waiting group (HR = 0.35, P < .0001) but no different vs the rituximab maintenance group (HR = 0.75, P = .33).
Quality-of-Life Outcomes
There was a significant improvement in the Mental Adjustment to Cancer scale score from baseline to month 7 in the rituximab maintenance group and no significant change in the watchful waiting group (P = .0004 for difference in change) and no change vs decline in scores for Illness Coping Style (P = .0012 for difference). Patients in the rituximab maintenance group also reported significantly less worry about the need for treatment (P = .0037 for difference).
There were no other clinically significant differences between the two groups in any other quality-of-life measure, with all scores in both groups either improving or remaining unchanged at 7 months.
Adverse Events
There were 18 serious adverse events considered at least possibly related to study treatment in the rituximab groups (4 in the induction group and 14 in the maintenance group), consisting of infection in 9 patients (8 in maintenance group), allergic reaction in 5 (2 in maintenance group), and neutropenia in 4 (all in maintenance group). Of these, 12 adverse events were grade 3 or 4, including infection in 5 patients, neutropenia in 4, and allergic reaction in 3.
The investigators concluded, “Rituximab monotherapy should be considered as a treatment option for patients with asymptomatic, advanced-stage, low-tumour-burden follicular lymphoma.”
Kirit M. Ardeshna, FRCP, of University College Hospital, London, is the corresponding author for The Lancet Oncology article.
The study was funded by Cancer Research UK, Lymphoma Research Trust, Lymphoma Association, and Roche. For full disclosures of the study authors, visit www.thelancet.com.
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