Association between regular molecular monitoring and tyrosine kinase inhibitor therapy adherence in chronic myelogenous leukemia in the chronic phase

Abstract

Objective:

Adherence with oral tyrosine kinase inhibitor (TKI) therapy over prolonged timeframes is required for successful outcomes among patients with chronic phase chronic myelogenous leukemia (CP-CML). Since quantitative polymerase chain reaction (qPCR) monitoring may identify early suboptimal responses, and thereby permit detection of non-adherence to therapy, we sought to assess the association between frequency of molecular monitoring and medication adherence.

Research design and methods:

This is a retrospective cohort study design of diagnosed CP-CML obtained from two large US administrative claims databases. Patients were grouped into cohorts based on the number of qPCR tests they had. Adherence was assessed both by medication possession ratio (MPR) and proportion of days covered (PDC) and was compared between qPCR cohorts. A sensitivity analysis was performed by adjusting for the number of oncology outpatient visits not due to routine molecular monitoring.

Results:

Over the 12 month study period, 1205 CML patients met the selection criteria; 41.0% had no qPCR tests, 31.9% had 1–2 tests, and 27.1% had 3–4 tests; 88.9% of patients were initiated on imatinib. Patients in the 3–4 qPCR tests cohort had an average MPR that was 10.22 (p < 0.001) and 9.54 (p < 0.001) percentage points higher compared to patients in the 0 tests cohort and the 1–2 tests cohort. When using PDC as a measure of adherence, similar results were obtained. The results of the sensitivity analysis were consistent with core analysis findings, excluding number of physician visits as a potential driver of adherence.

Limitations:

These findings demonstrate an association, not causation, between molecular monitoring frequency and adherence.

Conclusions:

Frequent molecular monitoring (3–4 times per year as recommended in current guidelines) is associated with greater TKI treatment adherence for patients diagnosed with CML. Since TKI adherence >80% has been associated with better clinical outcomes, this study underscores the importance of molecular monitoring.

Keywords::

• Chronic myelogenous leukemia
• Medication adherence
• Quantitative real time polymerase chain reaction
• Tyrosine kinase inhibitor

Transparency

Declaration of funding

This study was sponsored by Novartis Pharmaceuticals Corporation.

Declaration of financial/other relationships

S.L.G. has disclosed that he is a consultant for and received research funding from Ariad Pharmaceuticals, Bristol Myers Squibb and Novartis Pharmaceuticals Corporation. L.C. has disclosed that she/he is an employee of Novartis Pharmaceuticals Corporation. A.G., K.D., and E.Q.W. have disclosed that they are employees of Analysis Group Inc., which has received consultancy fees from Novartis Pharmaceuticals Corporation.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

We thank Ana Bozas, an employee of Analysis Group Inc., who contributed to the preparation and editing of the manuscript.

Previous presentation: This study was presented at the 2013 American College of Clinical Pharmacy (ACCP) Annual Meeting, Albuquerque, New Mexico, 13–16 October 2013.