Quality of Life and Adherence to Tyrosine Kinase Inhibitors Among Adolescent and Young Adult Chronic Myelogenous Leukemia Patients: A Systematic Review

Background:

The standard of care for patients with Chronic Myelogenous Leukemia (CML) is life-long treatment with tyrosine kinase inhibitors (TKIs). The chronic nature of the disease could impact patients' health-related quality of life (HRQOL). In addition, the need for indefinite oral medications poses a risk to low or non-adherence overtime. There is sparse literature surrounding CML in adolescents and young adults (AYA). This systematic review seeks to analyze HRQOL and adherence to tyrosine kinase inhibitors (TKIs) among AYA CML patients.

Methods:

This systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Inclusion criteria for articles included: patient reported outcomes, HRQOL, and medication adherence of children and AYA patients who were being treated with a TKI. Treatment for CML other than TKIs were excluded. Randomized controlled trials, cohort studies, case control studies, and retrospective chart review and pilot studies were the types of studies included. Case reports, abstracts, and articles published in a language other than English were excluded. As CML is more common in adult patients, studies that included adult data (age >39 years) were included only if the data was analyzed and reported independently in patients aged 39 years or younger, or if the median age of the reported results were from patients 39 years or younger. A search of the literature was conducted of the following databases: PubMed MEDLINE, Cochrane Library, EMBASE, CINAHL, and PsycINFO. There was no publication date restriction for our search criteria. The abstract screening and full-text screening were completed in a blinded fashion. The results were qualitatively studied by the authors of this paper; no statistical tests were conducted.

Results:

Initial abstract screening narrowed the articles to a total of 156. Full-text screening to assess for inclusion and exclusion criteria ultimately lead to the inclusion of 13 articles focused on HRQOL outcomes (n=5) and medication adherence (n=8). Regarding HRQOL among AYA with CML, there was heterogeneity in the findings among the included studies. For example, one study found that AYA CML patients reported better HRQOL scores compared to their older counterparts, whereas another study found the opposite. When compared to age matched controls from the general population, those with CML reported worse HRQOL scores. Another study found that when comparing at first diagnosis to follow up visits at 3- and 6-month intervals, HRQOL outcomes improved over time while on a TKI.

Regarding TKI adherence, there was variability in measurement tools for adherence. When measured as a percentage across studies, adherence ranged from 45-58% and when measured by the Medication Possession Ratio using pharmacy records, it was found to be 95-99%. Increased TKI adherence was significantly associated with better clinical outcomes, including improved cytogenetic response and in some studies, complete hematologic remission. There was a lack of uniformity on which covariates were significantly associated with increased TKI adherence. None of the studies included behavioral interventions to improve TKI adherence.

Conclusions: This is the first systematic review addressing TKIs adherence and HRQOL outcomes among CML AYA patients. Our findings could inform efforts to develop behavioral interventions to optimize TKI adherence and improve HRQOL outcomes in this vulnerable patient population.

No relevant conflicts of interest to declare.