Real-World Treatment Patterns and Molecular Response (MR) Among Patients with Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia (CML-CP) in a Large Community Oncology Setting
Authors: Zackon Ira , Beeks April , Wei David , Wentworth Chuck , Guo Jinhong , McDermott Courtney , Jadhav Kejal , Herms Lisa , Damon Andrea , Sadek Islam , Benton Christopher B. 
Published: December 2024

Background: Chronic myeloid leukemia (CML) marks one of the earliest successes of rational drug design based on the knowledge of a specific underlying molecular defect. ATP-competitive tyrosine kinase inhibitors (TKIs) targeting the ABL1 kinase activity of the BCR::ABL1 fusion protein are the current standard of care as the first treatment for chronic-phase CML (CML-CP). However, TKIs are associated with side effects that may require dose modifications, interruptions or change of therapy. Patients experiencing TKI intolerance or resistance may change treatments with often sub-optimal clinical response and outcomes. Current unmet needs in CML include reducing low-grade toxicities and treatment interruptions, as well as increasing rates of treatment-free remissions, particularly among newly diagnosed patients. It is therefore important to understand the real-world treatment patterns, treatment responses, and adverse events (AEs) of patients with CML-CP receiving their first TKI treatment in the community oncology setting, where most patients receive their care and physicians may see less CML patients as part of a general hematology/oncology practice.
Methods: This was a 6-year retrospective observational cohort study using structured and unstructured electronic health records data of adult patients newly diagnosed with CML-CP who initiated their first TKI treatment (imatinib, dasatinib, bosutinib, or nilotinib) (index date) within The US Oncology Network between January 1, 2016, and December 31, 2022. Patients were followed until last patient record or death, whichever occurred first by November 30, 2023. Descriptive analyses were conducted to evaluate patient and clinical characteristics, treatment patterns, and treatment response. The Kaplan-Meier method was used to assess duration of therapy (DOT). DOT was defined as the time between the index and end date of the first TKI treatment.
Results: A total of 500 eligible newly diagnosed CML-CP patients were included (mean age at index: 58.1 years; 54.0% male; 71.6% Caucasian). Median (interquartile range) follow-up post-index was 43.7 months (22.0, 64.3). Most patients had a baseline ECOG score of 0-1 (60.6%). The most common index treatment received was imatinib (47.0%), followed by dasatinib (35.2%), nilotinib (15.4%) and bosutinib (2.4%). The estimated median DOT of first TKI was 52.5 months (95% confidence interval: 38.0, 65.5). During the first TKI treatment, 129 patients (25.8%) required dose reduction, 88.4% due to AEs; 200 patients (40.0%) experienced treatment interruption, 73.0% due to AEs; and 233 (46.6%) patients discontinued their first TKI treatment, 53.6% due to AEs. The most common non-hematologic AE was fatigue (46.2%), nausea (31.6%), pain (30.8%), diarrhea (28.6%), and vomiting (9.4%). For hematologic AEs, anemia (23.8%) was most frequently reported, followed by thrombocytopenia and neutropenia (14.4% and 6.2%, respectively). By 12 months after the start of the first TKI treatment, 37.8% of patients achieved MMR (MR3, BCR::ABL1 ≤0.1%, or better) as the highest molecular response. Approximately a quarter of patients (24.4%) achieved or sustained MMR between 13 and 24 months from the start of the first TKI treatment. During the entire first TKI treatment, a total of 49.6% of patients achieved at least an MMR.
Conclusions: This large US community CML study shows that around a third of patients achieved an optimal response of MMR within the first year after initiating their first TKI treatment, suggesting sub-optimal treatment experience. Treatment modifications, largely because of AEs, were common. Furthermore, almost half the patients discontinued their first TKI treatment, highlighting a substantial unmet medical need among newly diagnosed CML patients, both from a tolerability and efficacy perspective. Findings from this study support the continued need for safer and more effective TKI in front-line treatment of CML-CP.