Real-world data vs pivotal trial outcomes of imatinib in newly diagnosed chronic myeloid leukemia patients.

e18565 Background: Chronic myeloid leukemia (CML) is driven by the BCR::ABL1 fusion gene, resulting in uncontrolled tyrosine kinase activity. The introduction of tyrosine kinase inhibitors (TKIs), beginning with imatinib, revolutionized CML treatment. Although pivotal clinical trials confirm the safety and efficacy of TKIs, trial populations may not fully represent the diverse patient populations encountered in real-world clinical practice. Methods: A systematic review of observational studies on newly diagnosed chronic-phase CML patients was conducted across five databases. Findings on patient demographics and treatment outcomes were compared to the IRIS trial, which demonstrated imatinib's superiority over interferon alfa plus cytarabine. The imatinib arms from pivotal trials of dasatinib (DASISION), nilotinib (ENESTnd), bosutinib (BFORE), and asciminib (ASC4FIRST) were also included in the trial cohort. Results: The RWD analysis included 21 studies from 16 countries. Geographic distribution varied between the RWD and trial cohorts, with RWD studies primarily including patients from Asia (33.3%), Europe (28.6%), and North America (19.0%), while patients from Africa and South America were underrepresented in both the RWD and trial cohorts. Notably, the RWD cohort included a younger patient population (46.6% vs. 50.5% years), a more balanced gender distribution (1.3:1 vs. 3:2), a higher prevalence of splenomegaly (62.2% vs. 18.5%), and a greater proportion of patients with high-risk Sokal scores (25.8% vs. 22.6%). Treatment outcomes revealed several differences between the cohorts. The trial cohort demonstrated a higher rate of partial cytogenetic response at three months compared to the RWD cohort (62.9% vs. 59%). However, the rates of complete cytogenetic response (CCyR) at 12 months were similar, with the trial cohort (64.8%) and the RWD cohort (65.1%). At 18 months, the trial cohort showed higher CCyR rates (80.8% vs. 53.5%). At 12 months, major molecular response (MMR) rates were higher in the RWD cohort (53.2% vs. 31.7%) but exhibited greater variability across studies (38%–68.1%) compared to the more homogeneous trial data (22%–40.2%). By 18 months, MMR rates were higher in the trial cohort (56.4% vs. 39.1%). Five-year overall survival rates were comparable between the two groups, with the RWD cohort at (92.4%) and the trial cohort at (92.1%). Conclusions: Significant differences in patient demographics, risk profiles, and treatment outcomes were observed between RWD and trial cohorts. Despite lower rates of CCyR and MMR in RWD, long-term survival outcomes were similar across both groups. These findings underscore the importance of RWD in evaluating treatment effectiveness and highlight the need for increased diversity in clinical trial populations to ensure broader applicability of clinical findings.