Health Care and out-of-Pocket (OOP) Costs Among Medicare Beneficiaries Diagnosed with Chronic Myeloid Leukemia (CML)
Authors: Kenzik Kelly , Bhatia Ravi , Williams Grant R , Bhatia Smita 
Published: October 2019

Abstract
Background: Patients with CML require treatment with Tyrosine Kinase Inhibitors (TKIs) for extended periods of time. Given a median age at diagnosis of 67, it is important to understand the costs incurred by the healthcare system (i.e., Medicare) as well as OOP costs incurred by the older CML patients treated with TKI. Previous studies have focused on the younger patient population (<65y) or have used simulation to estimate costs in older adults. We examined costs to Medicare and OOP costs in older CML patients over the first 2y from CML diagnosis in the TKI era.
Methods: We used SEER-Medicare data to identify 805 Medicare beneficiaries with incident CML diagnosed between 2007 and 2012 at age >65. A non-cancer Medicare beneficiary sample (n=805) was age, sex, and race frequency-matched to CML patients. Patients were followed until 2y from diagnosis; death or 12/31/2014, whichever came first. Therapeutic exposures were classified as: i) TKIs (Imatinib, dasatinib, nilotinib); ii) other outpatient chemotherapy (CT) without TKI; iii) no treatment. Primary outcomes were healthcare costs reimbursed by Medicare and patient-paid OOP costs. Statistical Analysis: Survival was estimated using Kaplan-Meier method and Cox survival models for adjusted analyses (age, sex, race/ethnicity, treatment, State-buy in coverage and comorbidity). Costs were estimated monthly using generalized linear models with log link (gamma distribution) with bootstrapping to obtain 95% confidence intervals (95%CI). To accommodate censoring, each one-month cost was weighted by inverse probability of not being censored. Monthly costs were summed over 24 mo and averaged to generate annual costs. Predictors of high cost were calculated. Proportion of resource-specific costs (inpatient, outpatient, Part D [prescription drug coverage], home health, and durable medical equipment costs) were compared across treatment categories. Costs were adjusted to reflect 2018 pricing. Models were evaluated for the following 3 eras: 2007-2008 (35%), 2009-2010 (32%), and 2011-2012 (33%).
Results: Median age at diagnosis was 76y (66-102) and 5yr survival was 56%. Majority of patients were white (83%) and male (53%); 20% had State-buy in coverage; 36.6% had ≥1 comorbidity. Overall, 52.4% received TKI therapy (43% received Imatinib alone); 27% received other CT; 21% received no treatment. Patients receiving TKI were 57% less likely to die than patients receiving no CT over 3y from diagnosis (HR=0.43, 95%CI, 0.31-0.62), and 65% less likely to die compared to patients receiving other CT (HR=0.36, 95%CI, 0.26-0.49). Medicare costs: Annual Medicare cost/patients was significantly higher for TKI-treated patients ($83,037) vs. patients with other CT ($35,996), patients with no CT ($22,813), and non-cancer controls ($11,506) (Fig 1). The average annual cost/patient increased significantly across the 3 eras for TKI patients ($65,102 to $112,118, p<0.001), but declined for patients treated with other CT ($42,575 to $27,533, p<0.01). Predictors of being >90th percentile in cost ($150,241) included having State-buy in coverage (RR=1.9, p<0.001); and receiving Imatinib alone (RR=5.4, p=0.004), or other multiple TKIs (RR=10.9, p<0.001) (ref grp: no treatment). As shown in Fig 2, the largest proportion of annual costs was Part D (2007-2008: 56%; 2009-2010 60%; 2011-2012: 70%) for the TKI-treated patients but was inpatient care for those treated with other CT. Patient-paid OOP costs: Total annual OOP costs were ~2-times higher for TKI patients vs. other CT patients ($7,404 vs. $3,900), ~3-times higher vs. no CT patients, and 3.5-times higher vs. non-cancer controls (Fig 3). OOP costs for TKI patient remained consistently high across the 3 eras ($6,913 to $7,867), but declined for the other CT group ($4,929 to $2,996).
Conclusion: The superior survival in Medicare beneficiaries with CML is accompanied with significantly increasing costs to Medicare. Highest cost groups include those receiving multiple TKIs (i.e., dasatinib or nilotinib along with imatinib). The high costs are largely attributable to Part D in the TKI group. Patients receiving TKIs continue to experience a significant personal financial burden, with 3.5 times higher costs than non-cancer controls.

Disclosures
No relevant conflicts of interest to declare.