Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges

Abstract

BCR-ABL inhibitors for treating chronic myeloid leukemia in chronic phase have transformed a previously incurable malignancy into a manageable condition. However, suboptimal medication adherence has been observed with these agents affecting clinical outcomes and healthcare costs. In order to raise awareness of the problem of adherence, and before developing pragmatic strategies to enhance medication adherence, a deep understanding of the best approaches for measuring adherence in chronic myeloid leukemia patients and identifying non-adherence is required. A systematic literature review on the prevalence, measurement methods, consequences and risk factors for non-adherence to BCR-ABL inhibitors and adherence-enhancing interventions was performed and critically appraised. Of the 19 included articles, 9 were retrospective. Average adherence varied from 19% to almost 100% of the proportion of prescribed drug taken, but it was measured through various different methods and within different study groups. Suboptimal adherence was associated with a negative impact on both clinical and economic outcomes. There is a lack of supportive evidence demonstrating a difference in adherence across BCR-ABL inhibitors and even contradictory results between the 2(nd) generation inhibitors. Drug-related adverse events and forgetfulness were common reasons for intentional and unintentional non-adherence, respectively, but further research is required to identify additional reasons behind non-adherence or patients at risk of non-adherence. Non-adherence in chronic myeloid leukemia patients treated with BCR-ABL inhibitors is common and associated with critical outcomes. However, this review highlights important existing gaps, reveals inconsistent definitions, and a lack of standardized methods for measuring adherence in chronic myeloid leukemia. All require further investigation.

Figure 1.

Flow diagram of included studies. The analysis was performed on 19 articles, whereas abstracts were only considered for inclusion in the Discussion.

Figure 2.

Patient treatment duration between studies.

Figure 3.

Methods used to measure adherence per type of study. Mixed refers to a combination of methods (e.g. a questionnaire in combination with MEMS® [Medication Event Monitoring Systems] or in combination with pill count and appointments kept).

Figure 4.

Adherent and non-adherent groups of patients in studies. MMAS: Morisky Medication Adherence Scale; MEMS®: Medication Event Monitoring Systems; MPR: medication possession ratio; BAAS: Basel Assessment of Adherence Scale with Immunosuppressive Medication.,,–,,

Figure 5.

Impact on clinical outcomes. (A) Impact on cytogenetic response. (B) Impact of poor adherence on event-free survival.,