Rituximab Versus Watchful Waiting for Asymptomatic Advanced-Stage Low-Tumor-Burden Follicular Lymphoma: A Systematic Review and Meta-Analysis.

The optimal initial management of asymptomatic patients with advanced-stage low-tumor-burden follicular lymphoma (LTB-FL) remains uncertain. Although watchful waiting (WW) has historically been the standard approach, rituximab monotherapy has emerged as an alternative strategy. A systematic review and meta-analysis comparing rituximab monotherapy with WW was performed in this population. PubMed, Embase, and Cochrane Library were systematically searched for studies comparing rituximab monotherapy with WW in adult patients with advanced-stage LTB-FL. The primary outcome was overall survival (OS), while secondary outcomes included histological transformation (HT) and time to new treatment (TTNT). Statistical analyses were conducted using Review Manager version 5.4 with random-effects models, and heterogeneity was assessed using the I² statistic. Three studies, including 2 randomized controlled trials and one observational study, comprising 1590 patients, were included. For OS, analysis demonstrated no statistically significant difference between rituximab and WW (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.70-1.12; P = .31; I² = 0%). Similarly, rituximab was not associated with a statistically significant reduction in HT (risk ratios 0.84, 95% CI 0.60-1.16; P = .29; I² = 0%), although the pooled estimates for OS and HT numerically favored rituximab. TTNT was significantly prolonged with rituximab compared with WW (HR 0.50, 95% CI 0.41-0.61; P < .00001; I² = 0%). Early rituximab monotherapy was not associated with improved OS or a significant reduction in HT compared with WW in asymptomatic patients with advanced-stage LTB-FL, although it prolonged TTNT. Further prospective studies are warranted to define the long-term clinical impact of early rituximab.