title: Randomized controlled trials in relapsed/refractory follicular lymphoma: a systematic review and meta-analysis.
abstract: This systematic literature review evaluated the clinical efficacy and safety of interventions used in relapsed/refractory follicular lymphoma. Primary efficacy outcomes were objective response rate, progression-free survival and overall survival. Safety endpoints were grade 3/4 toxicities, serious adverse events and withdrawals or deaths due to toxicity. Studies were selected if they were randomized controlled trials reporting on the efficacy or safety of treatments for relapsed or refractory follicular lymphoma, and if outcomes were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 10 randomized controlled trials of treatments for relapsed/refractory follicular lymphoma. The most prominent drug investigated (alone or in combination) was rituximab. Most trials did not report median overall survival. Two trials reported median event-free survival (range, 1.2-23.2 months). Six of ten trials reported objective response rate (range, 9-93%). Meta-analysis showed only one statistically significant result: rituximab + bortezomib yielded a significantly higher objective response rate than rituximab monotherapy (relative risk, 1.28; 95% confidence interval, 1.11-1.47). Otherwise, there were no discernable differences in overall survival or progression-free survival, partly due to insufficient reporting of results in the clinical trials. The relatively small number of randomized controlled trials, few overlapping treatment arms, and variability in the randomized controlled trial features and in the endpoints studied complicate the formal comparison of therapies for relapsed/refractory follicular lymphoma. Additional well-designed randomized controlled trials are needed to fully understand the relative outcomes of older and more recently developed therapies.
authors: Medical College of Wisconsin, Milawukee, USA.
authors: Rachel L
authors: RL
authors: Police
authors: Medical College of Wisconsin, Milawukee, USA.
authors: Peter C
authors: PC
authors: Trask
authors: Medical College of Wisconsin, Milawukee, USA.
authors: Jianmin
authors: J
authors: Wang
authors: Medical College of Wisconsin, Milawukee, USA.
authors: Robert
authors: R
authors: Olivares
authors: Medical College of Wisconsin, Milawukee, USA.
authors: Shahnaz
authors: S
authors: Khan
authors: Medical College of Wisconsin, Milawukee, USA.
authors: Adeline
authors: A
authors: Abbe
authors: Medical College of Wisconsin, Milawukee, USA.
authors: Ann
authors: A
authors: Colosia
authors: Medical College of Wisconsin, Milawukee, USA.
authors: Annete
authors: A
authors: Njue
authors: Medical College of Wisconsin, Milawukee, USA.
authors: Beth
authors: B
authors: Sherril
authors: Medical College of Wisconsin, Milawukee, USA.
authors: Rodrigo
authors: R
authors: Ruiz-Soto
authors: Medical College of Wisconsin, Milawukee, USA.
authors: James A
authors: JA
authors: Kaye
authors: Medical College of Wisconsin, Milawukee, USA mehdi.hamadani@gmail.com.
authors: Mehdi
authors: M
authors: Hamadani
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069286:Bortezomib / Q000627:therapeutic use*; D018572:Disease-Free Survival; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D000069283:Rituximab; D000069286:Bortezomib
keywords: Relapsed; follicular lymphoma; monoclonal antibody; refractory; treatment