OBJECTIVES: To compare the efficacy and safety of R² with bendamustine and rituximab (BR) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treatment of R/R FL using an MAIC.

METHODS: A systematic literature review of clinical trials and observational studies reporting survival and adverse events (AEs) of systemic treatments for R/R FL up to September 1, 2017 was conducted using MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov databases, and EU and US conference proceedings. Primary outcomes of interest were PFS and OS. AEs were analyzed including all-grade nausea/vomiting and grade ≥3 neutropenia.

Pseudo-individual patient data (IPD) generated from digitized KM curves were compared with actual IPD from the AUGMENT and MAGNIFY R² trials. An unanchored MAIC was conducted to adjust for potential effect modifiers and prognostic variables (EM/PV) between trials. Cox proportional hazards and parametric survival models were fitted to match-adjusted IPD and digitized KM data.

RESULTS: Aggregate data from 1 R-CHOP and 3 BR studies were compared with AUGMENT and MAGNIFY data. PFS did not significantly differ between R² and R-CHOP (HR 0.94, 95% CI 0.52–1.7; p=0.837) or R² and BR (HR 1.26, 95% CI 0.7–2.27; p=0.441). OS did not significantly differ between R² and R-CHOP (HR 0.77, 95% CI 0.25–2.43; p=0.660); OS data were unavailable for BR. No significant differences in AEs were observed between R² and BR except lower rates of nausea/vomiting for R² (17% vs 50%; OR 0.21, 95% CI 0.09–0.47; p=0.0001). Grade ≥3 neutropenia was 48% for R² vs 55% for R-CHOP (OR 0.77, 95% CI 0.42–1.40; p=0.386).

CONCLUSIONS: Consistent with the RELEVANCE trial, R² efficacy seems comparable with that of R-chemo in R/R FL. Point estimates varied depending on the ability to match for variables including prior rituximab exposure. Limitations include the inability to simultaneously adjust for all potential EM/PV.