Real-World Patterns of Tyrosine Kinase Inhibitor (TKI) Discontinuation and Reinitiation in Chronic Myeloid Leukemia (CML) Patients in the United States

OBJECTIVES: Clinical guidelines support discontinuing tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML) with deep molecular response. This study aims to investigate TKI discontinuation and reinitiation patterns in real-world settings in patients with CML in the US.

METHODS: We used the Merative MarketScan Commercial Claims and Medicare databases. Patients initiating TKI between January 2010 to June 2018 with a baseline CML diagnosis were identified. TKI discontinuation was defined as a gap of ≥60 days. Patients should be on continuous TKI therapy for three years to be included in this study. Baseline characteristics were measured from the year preceding the discontinuation period. Follow-up continued from discontinuation date until either reinitiation of TKI or disenrollment. Probabilities of discontinuation and reinitiation over time were measured using Kaplan-Meier estimates.

RESULTS: We identified 1,765 new users of TKI with a CML diagnosis, 1,546 of whom have been on continuous treatment for at least 3 years. Among them, 265 patients discontinued treatment, with 180 restarting TKI. The cohort's mean (SD) age was 57.8 (14.3) years, with 52.5% male. Imatinib (44.5%) was the most common TKI used before discontinuation, followed by dasatinib (26.8%) and nilotinib (22.6%). The median (IQR) time to discontinuation was 559 (204-1,035) days, and the probabilities of discontinuation at the 4th, 5th, and 6th years after initiation were 42%, 64%, and 81%, respectively. The median (IQR) length of discontinuation among those who reinitiated was 91 (70-153) days, and 50.0% and 83.9% reinitiated TKI within 3 months and 6 months, respectively. Of the patients who reinitiated TKI, 49% restarted with imatinib, followed by dasatinib (21.6%) and nilotinib (20%).

CONCLUSIONS: This study highlights the real-world patterns of TKI discontinuation and reinitiation in CML patients. These findings can inform treatment strategies and improve patient outcomes by identifying critical factors in TKI discontinuation and reinitiation.