Neutropenia and neutropenic fever with polatuzumab vedotin for diffuse large B-cell lymphoma: Meta-analysis of randomized clinical trials.

Abstract

e19576 Background: Polatuzumab vedotin (POLA) is an antibody–drug conjugate composed of an anti-CD79b monoclonal antibody conjugated by a protease-cleavable linker to monomethyl auristatin E, a microtubule inhibitor. POLA has shown efficacy in patients with relapsed or refractory Diffuse large B-Cell lymphoma (DLBCL) and recently shown better progression free survival in previously untreated DLBCL as well. We conducted a meta-analysis of randomized controlled trials (RCTs) to determine the relative risk of neutropenia and febrile neutropenia associated with use of POLA regimens for DLBCL. Methods: We conducted a systematic search at PUBMED, EMBASE, and meeting abstracts as per PRISMA guidelines from 2010 until December 2021. Randomized controlled trial utilizing POLA for DLBCL were included. We used the Mantel-Haenszel (MH) method utilizing random effects model to calculate pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value. All statistical analyses were performed with Review Manager Version 5.4. Results: A total of 1073 patients from 3 RCT (1 Phase III and 2 Phase II Studies) were included in this study. The study arm used POLA-R-CHP (Rituximab, Cyclophosphamide, Doxorubicin, Prednisone), POLA-Rituximab, and POLA-BR (Bendamustine-Rituximab). The control arm used R-CHOP, Pinatuzumab-R, and BR respectively The overall incidence of neutropenia was 31.54% in POLA Group vs 32.94% in control group with RR 0.99 (95% CI: 0.69 – 1.42, P=0.97, I2=16%) whereas grade 3-4 neutropenia incidence was 29.24 vs 30.82 with RR 0.95 (95% CI: 0.79 – 1.16, P=0.65, I2=2%). The overall febrile neutropenia incidence was 12.87% in Polatuzumab group vs 7.90% in the control group with RR 1.62 (95% CI: 1.12 – 2.35, P = 0.01, I2=0%). Conclusions: Our study demonstrated that there was no statistical difference in risk ratio of any grade neutropenia (including grade 3-4) in both the arms. However, there was significantly increased risk of febrile neutropenia among patients who received Polatuzumab vedotin based treatment compared to those who did not. Further studies and long term follow up are necessary to define the actual relation and definitive incidence.[Table: see text]