Medication adherence, molecular monitoring, and clinical outcomes in patients with chronic myelogenous leukemia in a large HMO

Abstract

ObjectiveOur objective was to examine the association between adherence to tyrosine kinase inhibitors (TKIs) and molecular monitoring and the risk of disease progression or mortality among patients with chronic phase chronic myeloid leukemia (CML). DesignWe assembled a retrospective cohort of patients with CML (chronic phase, no prior cancer history, and confirmed to be Philadelphia chromosome positive) using data from electronic health records and chart reviews. Medication possession ratio (MPR) was used to measure drug adherence. SettingA large, community-based, integrated health plan in Southern California. ParticipantsThe cohort consisted of 245 adult patients (≥18 years old) with Philadelphia positive chronic phase CML diagnosed from 2001 to 2012 and followed through 2013. Main outcome measuresIn survival analyses, we examined the association of TKI adherence (MPR) and polymerase chain reaction (PCR) monitoring test frequency with the composite clinical outcome, progression to accelerated phase disease–blast crisis or mortality (progression-free survival). The cohort was followed for a maximum of 13 years (median 4.6 years). ResultsOver 90% of the cohort initiated TKI therapy within 3 months of diagnosis, and the mean MPR was 88% (SD 18%). Virtually all patients (96%) started on imatinib. The rates of progression to accelerated phase–blast crisis and mortality were lower in patients with greater TKI adherence (20.4/1000 person-years) versus lower adherence (27.0/1000 person-years). Patients who underwent PCR monitoring had a significantly reduced risk of progression or mortality, which was seen in patients with high and low TKI adherence status from both the groups (hazard ratio [HR] 0.07 [95% CI 0.03-0.19 if MPR >90%] and HR 0.70 [95% CI 0.02-0.21 if MPR<90%]). ConclusionOur results suggest that close clinical monitoring, which includes PCR monitoring in patients with high and low TKI drug adherence, is associated with a lower risk of progression or mortality.