Impact of Earlier Vs. Later Monitoring on Disease Progression and Economic Outcomes Among Patients with Chronic Myeloid Leukemia in the Real-World Setting

Introduction: The National Comprehensive Cancer Network recommends monitoring of patients with chronic myeloid leukemia (CML) beginning at diagnosis. Such testing is necessary for optimal treatment selection, however, patients are often not monitored until later in the course of disease or when clinical symptoms present. In this study, we evaluated the impact of molecular monitoring earlier in the course of disease as compared to later monitoring with the aim to determine a potential association between timing of monitoring and CML disease progression and healthcare resource utilization in a real-world setting in the US.

Methods: Patients (≥ 18 years of age) with ≥1 inpatient or ≥2 distinct outpatient (≥30 days apart) diagnoses for CML, January 01, 2006 through June 30, 2016, were identified from the MarketScan^® databases. Patients were defined as having disease progression based on the presence of treatments for advanced phase and blast crisis CML. A case control study design was used; cases were defined as patients with disease progression and patients not captured as having progression were identified as controls. Among cases, the index date was defined as the first date of treatment for CML progression and among controls, the index date was a randomly selected date (using simple random sampling) after the first CML diagnosis. Patients were required to have 24 months of continuous medical and prescription insurance coverage prior to the index date (baseline period). Patients were also required to have ≥1 CML monitoring test in the baseline period. Patients with earlier monitoring were identified as those with ≥1 monitoring test during the 7-24 months prior to the index date (Figure); patients with later monitoring were identified as those with ≥1 monitoring test only during the last 6 months prior to the index date and not during the 7-24 months prior to the index date (Figure). Patient demographics and clinical characteristics were evaluated during the baseline period. All-cause healthcare resource utilization and associated costs were evaluated per patient per month (PPPM) during the baseline period and a variable length follow-up period lasting ≥1 day and up to 1 year. Multivariate generalized linear modeling (GLM) was used to evaluate differences in all-cause healthcare costs between the earlier vs. later monitoring cohorts. Multivariate logistic regression was used to evaluate the association between monitoring status and progression.

Results: A total of 2,730 CML patients were identified, among which 60% (n=1,633) received earlier monitoring and 40% (n=1,097) received later monitoring only. The two groups were similar in terms of mean age and gender: 56 years vs. 57 years and 56% vs 57% females among patients with earlier vs. later monitoring, respectively. The mean Charlson Comorbidity Index score was lower among patients with earlier vs. later monitoring (3.15 vs. 3.41, p=0.0001), which indicates that patients with earlier monitoring were healthier. The three most frequently observed comorbid conditions of cardiovascular disease, gastrointestinal disease and lipid abnormalities were present in 67%, 62% and 44%, respectively, of patients with earlier monitoring vs. 71%, 66% and 52% of patients with later monitoring. Evidence of progression was present in 8.9% of patients with earlier monitoring, vs. 9.3% of patients with later monitoring. After the multivariable regression model was used to adjust for patient characteristics, patients with earlier vs. later monitoring were shown to be associated with a lower likelihood of CML progression (odds ratio: 0.715, confidence interval (CI) [0.530 - 0.964]; p=0.0280), during the follow-up period. After adjusting for covariates, the mean all-cause healthcare costs (PPPM) for inpatient (hospitalization), outpatient medical service, total (inpatient + outpatient) medical service, outpatient pharmacy and total healthcare were lower for patients with earlier monitoring as compared to those with later monitoring (Table).

Conclusion: Patients who are monitored earlier in the course of their disease may have better outcomes and lower total cost of care, as evidenced by the lower likelihood of CML progression and lower healthcare resource utilization in this group as compared to patients with later monitoring only.

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