Stefano Molica1, Diana Giannarelli2, Emili Montserrat3. 1. Department of Hematology-Oncology, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy. Electronic address: smolica@libero.it. 2. Biostatistics Unit, IRCCS Regina Elena, Rome, Italy. 3. Department of Hematology, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Abstract
BACKGROUND: Available targeted agents (TAs) for the upfront therapy of chronic lymphocytic leukemia (ie, ibrutinib, acalabrutinib, venetoclax) have rarely been compared in head-to-head clinical trials. In search of data for evidence-based treatment decisions, a systematic literature review and network meta-analysis was performed. MATERIALS AND METHODS: The screening process adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA). RESULTS: Only 3 trials were suitable for the base-case network analysis (ILLUMINATE, ELEVATE-TN, and CLL14). Regarding progression-free survival (PFS), fixed-effect analyses comparing ibrutinib-obinutuzumab (IO) with venetoclax-obinutuzumab (VO) (relative risk [RR], 1.52; 95% confidence interval [CI], 0.82-2.81), acalabrutinib (A) with IO (RR, 0.87; 95% CI, 0.47-1.61), and A with VO (RR, 0.57; 95% CI, 0.32-1.01) revealed that the upper limit of the 95% CI for RR did exceed the 1.0 value. This indicates a lack of significant difference in PFS for IO, VO, and A. In contrast, acalabrutinib plus obinutuzumab (AO) improved PFS in comparison with IO (RR, 0.43; 95% CI, 0.22-0.87) and VO (RR, 0.29; 95% CI, 0.15-0.56). No differences in the frequency of adverse events was observed across different TAs. Also, the analysis of PFS in relationship with high-risk genetic features (ie, TP53 aberrations, IGHV unmutated, 11q deletion) showed similar results for different TAs. However, patients with unmutated IGHV status fared better with AO than with VO in terms of PFS. CONCLUSIONS: This systematic review and network meta-analysis indicated that upfront AO prolongs PFS in comparison with IO and VO, whereas no differences are observed between IO, VO, and single-agent A. Hopefully, ongoing studies will further delineate the position of different TAs in chronic lymphocytic leukemia therapy based on effectiveness, availability, safety, cost, and treatment objectives.
BACKGROUND: Available targeted agents (TAs) for the upfront therapy of chronic lymphocytic leukemia (ie, ibrutinib, acalabrutinib, venetoclax) have rarely been compared in head-to-head clinical trials. In search of data for evidence-based treatment decisions, a systematic literature review and network meta-analysis was performed. MATERIALS AND METHODS: The screening process adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA). RESULTS: Only 3 trials were suitable for the base-case network analysis (ILLUMINATE, ELEVATE-TN, and CLL14). Regarding progression-free survival (PFS), fixed-effect analyses comparing ibrutinib-obinutuzumab (IO) with venetoclax-obinutuzumab (VO) (relative risk [RR], 1.52; 95% confidence interval [CI], 0.82-2.81), acalabrutinib (A) with IO (RR, 0.87; 95% CI, 0.47-1.61), and A with VO (RR, 0.57; 95% CI, 0.32-1.01) revealed that the upper limit of the 95% CI for RR did exceed the 1.0 value. This indicates a lack of significant difference in PFS for IO, VO, and A. In contrast, acalabrutinib plus obinutuzumab (AO) improved PFS in comparison with IO (RR, 0.43; 95% CI, 0.22-0.87) and VO (RR, 0.29; 95% CI, 0.15-0.56). No differences in the frequency of adverse events was observed across different TAs. Also, the analysis of PFS in relationship with high-risk genetic features (ie, TP53 aberrations, IGHV unmutated, 11q deletion) showed similar results for different TAs. However, patients with unmutated IGHV status fared better with AO than with VO in terms of PFS. CONCLUSIONS: This systematic review and network meta-analysis indicated that upfront AO prolongs PFS in comparison with IO and VO, whereas no differences are observed between IO, VO, and single-agent A. Hopefully, ongoing studies will further delineate the position of different TAs in chronic lymphocytic leukemia therapy based on effectiveness, availability, safety, cost, and treatment objectives.
Authors: Anthony R Mato; Matthew S Davids; Jeff Sharman; Lindsey E Roeker; Neil Kay; Arnon P Kater; Kerry Rogers; Meghan C Thompson; Joanna Rhodes; Andre Goy; Alan Skarbnik; Stephen J Schuster; Constantine S Tam; Toby A Eyre; Susan O'Brien; Chadi Nabhan; Nicole Lamanna; Clare Sun; Mazyar Shadman; John M Pagel; Chaitra Ujjani; Danielle Brander; Catherine C Coombs; Nitin Jain; Chan Y Cheah; Jennifer R Brown; John F Seymour; Jennifer A Woyach Journal: Clin Cancer Res Date: 2022-02-15 Impact factor: 13.801