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

Abstract

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. 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. 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. 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.