Best First Line Tyrosine Kinase Inhibitor for Chronic Phase Chronic Myeloid Leukemia in Adults: A Network Meta-Analysis

Background: For many years chronic myeloid leukemia (CML) remained a leukemic subtype in which little improvement was gained with regard to overall survival (OS). Imatinib, the first tyrosine kinase inhibitor (TKI), completely changed patients’ life expectancy. Although many studies have compared the use of imatinib and more recent TKIs in patients with newly diagnosed chronic phase (CP) CML, they have not established which is the most effective. Since there are no randomised controlled trials (RCTs) that compare head-to-head second- and third-generation TKIs, a network meta-analysis (NMA) is required to identify the best TKI to be preferably used. MethodsThis systematic review and NMA of RCTs will compare the efficacy and safety of imatinib vs second-generation (dasatinib, nilotinib, bosutinib) and third-generation TKIs (ponatinib) in adults with newly diagnosed Philadelphia Chromosome-Positive (Ph+) CP CML, concentrating on OS, progression-free survival (PFS), and hematological and non-hematological adverse events (AEs). The databases PubMed, EMBASE and Cochrane CENTRAL will be systematically searched, as well as other sources to identify published and unpublished studies. The risk of bias (RoB) of the included studies will be assessed using the Cochrane risk of bias tool; moreover, the confidence in network meta-analysis estimates will be evaluated with the CINeMA tool. DiscussionThe results of this systematic review and NMA are expected to suggest a specific TKI to be used for patients with newly CP CML. It remains valid that the choice of the optimal drug should consider AEs and co-morbidities as well as molecular/cytogenetic responses and transformation rates.Systematic review registrationThe review protocol PROSPERO registration number is: CRD42020190444. This protocol is written in accordance with the guidelines of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The PRISMA-P checklist can be found in Additional file 1.