Retrospective real-world comparison of clinical and economic burden between first-generation and second-generation tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML).

Abstract

e19030 Background: TKIs are the standard of care for the treatment of chronic phase CML under National Comprehensive Cancer Network (NCCN) guidelines. Imatinib is recommended as a first-generation TKI (1GTKI), and bosutinib, dasatinib, nilotinib, and ponatinib are recommended as second-generation TKIs (2GTKIs). TKIs are associated with high healthcare resource utilization (HRU) and costs, although literature is limited comparing 1GTKI and 2GTKIs in a U.S. population. Methods: Using the Veteran’s Health Administration (VHA) database between April 1, 2013 and March 31, 2018, the study included patients aged ≥18 years with ≥1 medical claim for CML and ≥1 prescription claim for a TKI on or after the initial CML diagnosis date during the identification period (October 1, 2014 to September 30, 2017); the first TKI prescription claim was defined as the index date. Inverse probability of treatment weighting (IPTW) minimized potential confounding; included variables were age, race, Quan-Charlson Comorbidity Index (CCI) score, and CHA2DS2-VASc Score. Medication possession ratio (MPR) assessed adherence to index TKI; optimal adherence was defined as MPR ≥80%. Results: 944 patients were included: 78.9% on 1GTKI and 21.1% on 2GTKI. Mean age was 62.21 years (SD:18.8); 77.2% were white. At baselinetients on 1GTKI had a higher comorbidity burden than 2GTKIs: COPD (19.7% vs. 8%; p < 0.01), anemia (17.7% vs. 11.1%; p = 0.02), GI symptoms (28.5% vs. 18.6%; p < 0.01), cardiac dysrhythmias (15.6% vs. 7.5%; p < 0.01), coronary artery disease (26.3% vs. 13.6%; p < 0.01), hypertension (55.7% vs. 43.2%; p < 0.01) and CHA2DS2-VASc Score (2.2 vs 1.6; p < 0.01). Optimal adherence was higher with 1GTKI (69.6% vs. 62.2%; p = 0.04), although this was not statistically significant when mean MPR was compared. During follow-up, no difference between 1GTKI and 2GTKIs patients occurred with cardiac-related risk factors or CHA2DS2-VASc Score. Compared to 1GTKI, 2GTKIs had lower medical (inpatient and outpatient) costs ($3,162 vs. $3,906; p = 0.04) but higher all-cause pharmacy cost ($7,214 vs. $3,895; p < 0.01) due to imatinib becoming a generic drug during the study period. CML-related ($2,260 vs. $1,640, p < 0.01) and cardiac-related medical costs ($1,365 vs. $665, p < 0.01) were significantly higher in 1GTKI vs. 2GTKIs patients. Conclusions: Adherence to TKI therapy was suboptimal for both 1GTKI and 2GTKIs. 2GTKIs incurred lower medical cost in comparison to 1GTKI. Differences in total all-cause cost was primarily driven by pharmacy cost of TKIs. These results show that, beyond the cost of the TKI, using a 2GTKIs in the first-line can lead to cost offsets when compared to imatinib.