Efficacy and Safety of New Anti-CD20 Monoclonal Antibodies Versus Rituximab for Induction Therapy of CD20⁺ B-Cell Non-Hodgkin Lymphomas: A Systematic Review and Meta-Analysis

Rituximab combined with chemotherapy is the first-line induction therapy of CD20positive B-cell non-Hodgkin lymphomas (CD20⁺ B-NHL). Recently new anti-CD20 monoclonal antibodies (mAbs) have been developed, but their efficacy and safety compared with rituximab are still controversial. We aimed to assess the efficacy and safety of new anti-CD20 mAbs compared with rituximab in the induction therapy of CD20⁺ B-NHL with a systematic review and meta-analysis. We searched MEDLINE, Embase, and Cochrane Library for eligible randomised controlled trials (RCTs) that compared new anti-CD20 mAbs with rituximab in induction therapy of B-NHL. The primary outcomes are progression-free survival (PFS) and overall survival (OS), additional outcomes include event-free survival (EFS), disease-free survival (DFS), overall response rate (ORR), complete response rate (CRR) and incidences of adverse events (AEs). Time-to-event data were pooled as hazard ratios (HRs) using the generic inverse-variance method and dichotomous outcomes were pooled as odds ratios (ORs) using the Mantel-Haenszel method with their respective 95% confidence interval (CI). Eleven RCTs comprising 5,261 patients with CD20⁺ B-NHL were included. Compared with rituximab, obinutuzumab significantly prolonged PFS (HR 0.84, 95% CI 0.73-0.96, P = 0.01), had no improvement on OS, ORR, and CRR, but increased the incidences of serious AEs (OR 1.29, 95%CI 1.13-1.48, P < 0.001). Ofatumumab was inferior to rituximab in consideration of ORR (OR 0.73, 95% CI 0.55-0.96, P = 0.02), and had no significant differences with rituximab in regard to PFS, OS and CRR. ¹³¹I-tositumomab yield similar PFS, OS, ORR and CRR with rituximab. ⁹⁰Y-ibritumomab tiuxetan increased ORR (OR 3.07, 95%CI 1.47-6.43, P = 0.003), but did not improve PFS, DFS, OS and CRR compared with rituximab. In conclusion, compared with rituximab in induction therapy of CD20⁺ B-NHL, obinutuzumab can significantly improves PFS but with higher incidence of AEs, ofatumumab decrease ORR, ⁹⁰Y-ibritumomab tiuxetan increase ORR.