Response to Tyrosine Kinase Inhibitors in Real-World Patients With Chronic Myeloid Leukemia

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Szeto, A.H.
    • Affiliation: Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics
  • Bucci, T.
    • Affiliation: UNC Medical Center
  • Deal, A.
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Zhu, A.
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Ahmad, M.
    • Affiliation: UNC Medical Center
  • Cass, A.S.
    • Affiliation: UNC Medical Center
  • Sketch, M.R.
    • Affiliation: Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics
  • Kemper, R.
    • Affiliation: Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics
  • Zeidner, J.F.
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Foster, M.C.
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Muluneh, B.
    • Affiliation: Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics
  • Crona, D.J.
    • Affiliation: Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics
Abstract
  • Background: Tyrosine kinase inhibitors (TKIs) are the front-line therapy for chronic myeloid leukemia (CML), where phase 3 clinical trials have demonstrated their safety and efficacy. However, trial patients may not be representative of real-world patients (RWPs). Objective: To evaluate RWP clinical factors associated with effectiveness and safety in CML patients treated with TKIs. Methods: Patients with CML treated with at least 30 days of imatinib, dasatinib, nilotinib, or bosutinib between 2014 and 2018 were included. Patients were stratified into categories based on the number of factors that would have precluded enrollment into pivotal TKI phase 3 trials (0, 1, ≥2). End points included complete hematologic response (CHR), early molecular response (EMR), major molecular response (MMR), adverse event (AE)-induced dose decreases, treatment interruptions, and treatment discontinuations. Results: Final analyses included 174 patients. Patients with ≥2 factors had a higher risk of dose decreases (relative risk = 1.54; 95% CI = 1.02-2.34; P = 0.02) and a shorter time to dose decrease (hazard ratio = 2.43; 95% CI = 1.23-4.97; P = 0.006) compared with patients with 0 factors. Significant differences were observed in CHR at 1 month and MMR at 3 months between patients with 0 and ≥2 factors (P = 0.03 and P = 0.04, respectively). Conclusion and Relevance: Approximately 60% of our RWPs would have been excluded from the pivotal phase 3 TKI trials. These data suggest that RWPs require more precise dosing to achieve CML clinical milestones and to mitigate AEs, but findings should be validated prospectively.
Date of publication
Keyword
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
License
  • Attribution 4.0 International
Journal title
  • Annals of Pharmacotherapy
Language
  • English
Version
  • Publisher
Funder
  • Pfizer; Merck; Celgene; University of North Carolina, UNC; Takeda Pharmaceuticals U.S.A., TPUSA; Eshelman Institute for Innovation, University of North Carolina at Chapel Hill; Agios Pharmaceuticals; Daiichi-Sankyo
ISSN
  • 1060-0280
Publisher
  • SAGE Publications Inc.

Relations

Parents:

This work has no parents.

In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details 10600280211044160.pdf 2022-02-08 Public Download