The Healthcare Resource Utilization, Costs, and Predictors of Progression Among Relapsed and Refractory CLL Patients

Background: Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia where the majority of patients (pts) experiences a relapse or becomes refractory after a first-line treatment. This study assesses the economic burden associated with early vs late disease progression among pts with relapsed and refractory (R/R) CLL and identifies factors that are associated with further disease progression.

Method: CLL pts with an indicator of R/R disease were selected from the Truven MarketScan database (>25 million commercially insured lives annually; 2000-2013) based on diagnoses and treatment patterns. Pts were ≥18 years in age, continuously enrolled in their health plan for ≥6 months prior to (baseline period) and ≥1 month after the first indicator of R/R CLL. The index date was defined as the date of the first R/R indicator. As a first step, pts who progressed following the first indicator of R/R CLL were identified and classified into two mutually exclusive cohorts: 1) pts with early progression (<12 months after index date) and 2) pts with late progression (≥12 months after index date). Healthcare resource utilization (HRU) and costs ($2013 US) were measured over the period from index date up to end of continuous healthcare plan enrollment (study period) and were compared between early vs late progression cohorts using multivariate generalized linear regression models. HRU and costs were reported per-pt-per-month (PPPM). As a second step, the full sample of pts with R/R CLL was used to identify factors associated with a risk of early progression using Cox proportional hazard models.

Results: Of the 4,387 R/R CLL pts selected, 2,238 (51%) pts had a progression following the first indicator of R/R CLL. Median time to first progression following the index date was 14.5 months. Among pts who progressed, 69.3% had early progression and 30.7% had late progression. Characteristics of pts with early vs late progression were similar in terms of age, sex ratio, and region of residence. The main differences between cohorts were in terms of baseline comorbidities – a higher proportion of pts in the early progression cohort had hypertension, deficiency anemias, and coagulation deficiency. Quan Charlson Comorbidity Index (CCI) was also higher in the early progression cohort compared to the late progression cohort (2.61 vs 2.48, p<.01). Over the study period, the early progression cohort had higher HRU: 54% more inpatient (IP) admissions, 85% more IP days, 27% more emergency room visits, and 31% more outpatient (OP) visits (all p<.01) compared to the late progression cohort. After adjusting for baseline confounding factors, pts in the early progression cohort also had higher total healthcare costs by $3,008 PPPM (mean costs $8,018 vs. $4,639), mainly driven by higher OP (adjusted difference $1,838) and IP (adjusted difference $848) costs (all p<.01). Among the full sample of R/R CLL pts (4,387 pts), time between CLL diagnosis and the firs indicator of R/R CLL (< 12 months; HR=1.20), and comorbidities, including a higher CCI (CCI≥3; HR=1.19), rheumatoid arthritis (HR=1.49), and substance-related and addictive disorders (HR=1.94) were found to be significantly associated with a higher risk of early progression. Results were generally consistent with a sensitivity analysis, where early vs late progression was defined using a 6-months cut-off.

Conclusions: R/R CLL pts who experienced early progression had more comorbidities and incurred significantly higher healthcare resources and costs than pts with late progression, suggesting that delaying progression in the fast progressing R/R CLL pts can reduce the economic burden. Time from CLL diagnosis to R/R CLL and comorbidities were the main predictors of early progression.