CML-479: Systematic Literature Review of Treatment Patterns, Long-Term Efficacy, and Safety of Dasatinib Therapy for Patients with Chronic Myeloid Leukemia

Abstract

Objectives: The tyrosine kinase inhibitors (TKIs) imatinib, dasatinib, and nilotinib are approved for the treatment of chronic myeloid leukemia (CML). It is important to evaluate differences in efficacy and safety of TKIs to help guide first-line (1L) treatment decisions. The objective of this review was to assess the treatment patterns, long-term efficacy, and safety of dasatinib compared with imatinib and nilotinib in CML. Methods: A systematic literature review (SLR) was conducted by searching Embase®, MEDLINE®, and Cochrane databases (Jan 2010 – Jul 2020). Searches of key congress abstracts (2017–2020) were performed using PRISMA guidelines and the Population, Intervention, Comparator, Outcome (PICO) criteria. Eligible interventional and real-world evidence (RWE) studies describing the treatment and switching patterns, efficacy, and safety were selected. Results: Of 224 records identified, 119 reported switching or discontinuation in ≥1L settings, and 128 reported the safety and efficacy of 1L dasatinib. Discontinuation rates for dasatinib were lower than those for imatinib and nilotinib (17/22 studies). Dasatinib elicited a faster, deeper molecular response than imatinib (3/3 randomized clinical trial studies) but a similar response to nilotinib (6/6 RWE studies). Achieving an early molecular response at 3 months (n=6) or a major molecular response (MMR) at 12 months (n=7) correlated with increased 5-year overall survival (R2=0.5946 and 0.8415, respectively). Sustained use of 1L dasatinib led to improved MMR and survival. Hematologic adverse events (AEs) were similar between dasatinib and imatinib in RWE studies (n=4; 15%–50% vs 15%–40% grade 3 AEs, respectively), but certain hematologic AEs (e.g., thrombocytopenia) were higher in clinical trials (n=4). Across all studies, cardiovascular and gastrointestinal AEs were higher in patients receiving nilotinib than dasatinib. Conclusions: This SLR demonstrates that dasatinib remains an effective long-term option for 1L treatment of patients with CML, with a lower incidence of non-hematologic AEs compared with imatinib or nilotinib. Moreover, patients were more likely to remain on dasatinib, leading to improved outcomes. Funding: Funded by Bristol Myers Squibb, Princeton, NJ, USA. Previous presentation: Reprinted from Harricharan S et al. Value Health 2021;24(suppl 1):S23. Copyright 2021, with permission from Elsevier.