Cardiovascular impact of switching to asciminib in chronic-phase chronic myeloid leukemia
S Miyazaki, T Takaku, E Sato, N Watanabe, M Ando, T MinaminoAbstract
Background
Among adenosine triphosphate-competitive tyrosine kinase inhibitors (ATP-TKIs) approved for chronic-phase chronic myeloid leukemia (CP-CML), nilotinib and ponatinib are associated with a high incidence of vascular adverse events, and cardiovascular monitoring is recommended in current cardio-oncology guidelines. In contrast, monitoring strategies for asciminib, a recently approved specifically targets the myristoyl pocket (STAMP) inhibitor, have not been addressed, and its real-world vascular impact remains unclear.
Purpose
To compare surrogate markers of atherosclerosis before and after switching from ATP-TKIs to asciminib in patients with CP-CML.
Method
This single-centre retrospective observational study included patients with CP-CML followed at a dedicated cardio-oncology clinic. Patients switched from ATP-TKIs to asciminib were identified. Arterial stiffness parameters, including cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI), were assessed before and after the switch. Cardiovascular events during follow-up were recorded.
Results
Among 102 patients in the cardio-oncology database, 45 were switched to asciminib. Thirty-two patients had complete arterial stiffness data before and after switching. Mean age at switching was 59.4 ± 12.8 years, and 65% were male. Approximately half had hypertension. No cardiovascular events requiring therapeutic intervention occurred during follow-up. ABI showed no significant change. In contrast, CAVI, a marker of arterial stiffness, showed a significant increase after asciminib initiation. Before switching, 21 patients had normal values (<8.0), 5 were borderline (8.0–8.9), and 6 were abnormal (≥9.0). Only one patient worsened from the normal to abnormal range.
Conclusion
Asciminib was not associated with clinically overt cardiovascular events in this cohort; however, a significant increase in arterial stiffness as assessed by CAVI was observed after treatment initiation. Given the age dependency of CAVI, causality cannot be confirmed. Larger studies are warranted to determine whether early increases in arterial stiffness are associated with future cardiovascular events and to clarify the need for vascular monitoring in these patients.