What question did this study set out to answer?

To analyze the outcomes of different tyrosine kinase inhibitors in chronic myeloid leukemia over 16 years.

July 17, 2026

Longitudinal analysis of tyrosine kinase inhibitor therapy outcomes and BCR‐ABL1 transcript decline velocity in chronic myeloid leukemia: A 16‐year real‐world study

MAMoaath K. Mustafa AliCleveland Clinic EZEmily C. ZaborCleveland Clinic Lerner College of Medicine KAKamilla AbdurakhmanovCleveland Clinic Lerner College of Medicine

Key Points

To analyze the outcomes of different tyrosine kinase inhibitors in chronic myeloid leukemia over 16 years.
Retrospective cohort study of 349 patients with chronic and accelerated-phase CML from 2007 to 2023.
Compared survival metrics and BCR-ABL1 transcript decline across first-, second-, and third-line TKIs.
Employed multivariable regression and time-dependent Cox models to adjust for confounders.
Five-year overall survival ranged from 78% for dasatinib to 90% for nilotinib, with nilotinib improving OS (HR, 0.43) and event-free survival (HR, 0.48).
Nilotinib showed the fastest decline in BCR-ABL1 transcript (β = -8.3%) compared to imatinib.
No significant differences in outcomes were noted for second- and third-line therapies.

Abstract

Abstract Background No large, randomized trials have compared three or more tyrosine kinase inhibitors (TKIs) in a single chronic myeloid leukemia (CML) cohort. Most studies are two‐arm comparisons versus imatinib, or rely on indirect methods. Methods A retrospective cohort study was conducted of 349 patients with chronic‐ and accelerated‐phase CML treated between 2007 and 2023 at Cleveland Clinic centers in Northeast Ohio. Overall survival (OS), event‐free survival (EFS), 12‐month therapeutic milestone achievement, and BCR‐ABL1 transcript decline velocity across first‐, second‐, and third‐line TKIs were compared. Baseline demographics, comorbidities, cytogenetics, and hematologic parameters were collected. Multivariable regression and time‐dependent Cox models were adjusted for confounders and varying therapy initiation times. Results First‐line TKIs included imatinib (53%), dasatinib (30%), nilotinib (15%), and bosutinib (2%). Median age ranged from 52 to 60 years, most patients were White, and high‐risk cytogenetics were rare. Five‐year OS ranged from 78% for dasatinib to 90% for nilotinib, with nilotinib associated with improved OS (hazard ratio HR, 0.43) and EFS (HR, 0.48) and the fastest BCR‐ABL1 decline (β = −8.3%) versus imatinib. In second‐ ( n = 181) and third‐line therapy ( n = 91), no significant differences in outcomes were observed. Across all lines, time‐dependent modeling showed improved EFS only for nilotinib (HR, 0.61). Unadjusted OS was higher in patients starting treatment in 2007–2010 versus later periods but differences disappeared after adjustment. Conclusions Real‐world data indicate that imatinib achieves comparable response rates to newer TKIs, with durable survival. Nilotinib consistently shows faster BCR‐ABL1 decline and improved EFS overall, consistent with prior network meta‐analyses. Lack of improvement in OS over time suggests the need to investigate factors influencing long‐term outcomes in CML.

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