Ward MA, Fang G, Richards KL, Walko CM, Earnshaw SR, Happe LE, Blalock S. Treatment interruption and regimen change in first-generation vs. second-generation tyrosine kinase inhibitors used as first-line therapy for chronic myeloid leukemia. JHEOR. 2015 Apr;2(2):181-91.

Background: Previous research has shown that dose reductions and treatment interruptions are associated with worse failure-free survival in chronic myeloid leukemia (CML). However, treatment interruptions are commonly used in clinical trials of imatinib, dasatinib, and nilotinib to managed adverse events. The comparative rates of treatment interruptions and regimen changes between patients initiating first-line therapy with a first-generation tyrosine kinase inhibitor (1GTKI) vs. second-generation TKI (2GTKI) in a real-world setting are unknown.

Objective: The objective of this observational, retrospective, cohort study was to assess the association between patients newly initiating a TKI (1GTKI vs. 2GTKI) and (1) treatment interruption, and (2) regimen change.

Method: Patients newly initiating 1GTKI or 2GTKI therapy between June 1, 2010 and December 31, 2011 in the Humana Research Database were included if this study if they were continuously enrolled for 4 months during the baseline period, between the ages of 18 and 89 years old at the index date, and had a diagnosis for CML. Treatment interruption and regimen changes were compared between cohorts using Cox proportional hazard regression models to control for covariates. Treatment interruption was defined as a gap in any TKI pharmacy claim that is longer than an allowable refill gap plus days’ supply from the previous TKI medication claim. Regimen change was defined as 1) a prescription claim for a different TKI therapy, or 2) increase in dose for the same medication during the follow-up period. Patients were followed until the date of the outcome (treatment interruption or regimen change), end of enrollment, or the end of the 12 month follow-up period, whichever came first.

Results: There were 368 patients who met the inclusion criteria (1GTKI n=237, 2GTKI n=131). Patients in the 2GTKI cohort had a 48% higher risk of treatment interruption vs. the 1GTKI cohort in the adjusted analyses (hazard ratio=1.48, 95% confidence interval 1.08-2.02). The time to treatment interruption was significantly longer in the 2GTKI cohort. Approximately 19% of patients in both cohorts had a regimen change, but there were no differences in regimen changes between the two cohorts.

Conclusions: In this study from a single health plan population, treatment interruptions were more common among patients initiating therapy with a 2GTKI, yet regimen changes did not vary by generation of TKI. Future research should assess reasons for treatment interruption and investigate these associations in other populations.

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