(078) Risk Evaluation of Vascular Adverse Events in Chronic Myeloid Leukemia Patients Following First-Line TKI Therapy Initiation

Background: The introduction of imatinib, the first tyrosine kinase inhibitor (TKI), marked a substantial improvement in the treatment of chronic myeloid leukemia (CML), greatly benefiting patient outcomes. Subsequent second-generation TKIs, such as dasatinib and nilotinib, offered improvements in treatment by providing enhanced molecular responses and lower progression rates compared to imatinib. However, these later-generation TKIs have also raised concerns regarding long-term vascular adverse events (VAEs) associated with their prolonged use.

Objectives: To compare the risk of VAEs among CML patients treated with first-line therapy using dasatinib, nilotinib, or imatinib.

Methods: We conducted a retrospective cohort study using the Merative MarketScan Commercial Claims and Encounters, and Medicare Supplemental databases. Patients aged ≥18 years, diagnosed with CML between January 2010 and December 2020, and who initiated TKI therapy with imatinib, nilotinib, or dasatinib after their diagnosis, were included. Continuous enrollment for at least one year prior to initial TKI dispensing was required. Exclusions were made for patients who were diagnosed with any VAEs during the one-year baseline period or initiated TKI therapy prior to CML diagnosis. We identified comorbidities and medication history from the one-year baseline period claims. Outcomes were defined as the first diagnosis of any VAE event (primary diagnosis) within five years following TKI initiation. Propensity score matching was used to create comparable groups for dasatinib vs. imatinib and nilotinib vs. imatinib comparisons. Follow-up continued for up to five years or until the occurrence of any of the following events: a VAE, treatment discontinuation, medication switching, end of enrollment, or the study end (December 31, 2021). Cox proportional hazards regression was used to compare VAE risks.

Results: 3,442 patients met the enrollment criteria, of which 1,363 started on imatinib, 1,081 on dasatinib, and 554 on nilotinib. In the unadjusted cohort, the average ages were 55 for imatinib, 51 for dasatinib, and 51 for nilotinib treated groups. When compared to imatinib, the hazard ratio for VAEs was 1.01 (95% CI 0.69, 1.49) for dasatinib, and 1.15 (95% CI 0.69, 1.89) for nilotinib.

Conclusions: Our findings reveal no statistically significant differences in the risk of VAEs for CML patients treated with nilotinib and dasatinib compared to imatinib. This finding contrasts with previous studies and underscores the need for more comprehensive research on patient characteristics and factors influencing vascular outcomes associated with TKI use in CML therapy.