Supporting Adherence to Tyrosine Kinase Inhibitor (TKI) Therapy Among Patients with Chronic Myeloid Leukemia (CML)

Background: The availability of BCR-ABL1 TKIs for treating patients with CML has significantly improved patient outcomes; 5-year relative survival rates have increased dramatically, from 34.2% in 1995 (before the TKI era) to 66.9% in 2007-2013 (http://seer.cancer.gov/statfacts/html/cmyl.html; accessed July 10, 2017). However, education on treatment adherence, lifestyle modifications, and regular molecular monitoring is still needed to ensure that patients receive optimal disease management and to reduce the risk of TKI-related adverse events (AEs), including cardiovascular events. Improving treatment adherence may also lead to improved responses, including an increased likelihood of achieving a deep molecular response (Marin D, et al. J Clin Oncol . 2010;28(14):2381-2388), which has become a new goal of therapy because it can enable some patients to become eligible to stop treatment (Hughes TP, et al. Blood . 2016;128(1):17-23).

Methods: Key considerations related to treatment adherence and strategies for supporting adherence are summarized based on published data and the authors' clinical experience.

Results: Adherence to TKI therapy has been associated with several benefits, including improved responses to treatment, a decreased risk of disease progression or mortality, and reduced healthcare resource utilization and costs in patients with CML (Jabbour EJ, et al. Am J Hematol . 2012;87(7):687-691; Haque R, et al. J Am Pharm Assoc . 2017;57(3):303-310.e2). In studies of TKI adherence, it has been suggested that many patients do not take TKIs as prescribed for both intentional (eg, avoiding AEs) and unintentional (eg, forgetting) reasons (Efficace F, et al. Leuk Res . 2014;38(3):294-298); thus, strategies aimed to improve patients' levels of adherence should take into account each patient's individual circumstances. Educational efforts and regular molecular monitoring for rising BCR-ABL1 levels, which may be indicative of nonadherence, are key factors in promoting adherence. Additionally, to reduce the risk of unintentional nonadherence, it can be helpful to enlist the assistance of the patient's family, place the drug in a visible location, and use technology-based reminders (eg, on patients' phones); to reduce intentional nonadherence, AE management and supportive care can be valuable. To minimize AEs, healthcare professionals should be aware of patients' concomitant conditions (eg, diarrhea, which may impact electrolyte levels; maintenance of appropriate electrolyte levels is important for reducing the risk of cardiac arrhythmia with TKIs) and medications (for avoidance of drug-drug interactions), and patients should be educated on proper management of their relevant comorbidities (eg, glucose metabolism, cholesterol).

Conclusions: Proper adherence to treatment is important for treatment responses and outcomes in patients with CML receiving TKIs and may allow some patients to achieve a sustained deep molecular response and become eligible to stop treatment. Healthcare professionals can help improve patient outcomes through education and other strategies to promote adherence.