Evolution of Tyrosine Kinase Inhibitor Use and Molecular Response Patterns Across Lines of Therapy in Chronic Myeloid Leukemia: Real-world Evidence From Brazil
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Despite advances in chronic myeloid leukemia (CML) management, real-world evidence (RWE) on treatment sequence and molecular response patterns across lines of therapy (LoT) remains limited in Brazil, particularly among after frontline tyrosine kinase inhibitors (TKI) exposure. Aim To characterize treatment sequence and molecular response patterns across LoT in patients with Philadelphia chromosome-positive CML treated in routine clinical practice in Brazil. Material and methods This retrospective observational study used anonymized electronic medical records from the iHealth Group database, including data from healthcare institutions across Brazil (2008–2026). Adults (≥ 18 years) with Philadelphia chromosome–positive CML who received treatment with a TKI were identified based on ICD-10 code C92, CML-related diagnostic terminology, and/or positive BCR::ABL1 RT-PCR results. TKI exposure (imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and asciminib) was identified through natural language processing (NLP)-based extraction of medication records. Patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) or ALL-directed chemotherapy were excluded. LoT were derived from longitudinal TKI treatment records using predefined rules, and analyses were restricted to patients with assignable treatment lines. The study was approved by an independent ethics committee. Results Of the 1,110 patients in first-line (1L), 238 (21.4%) progressed to second-line (2L) treatment, while only 28 (2.5%) received third-line (3L) therapy, indicating substantial attrition across successive treatment lines. Imatinib predominated in the 1L therapy (83.3%), whereas nilotinib (47.9%) and dasatinib (41.2%) represented the majority of 2L treatment. In 3L, nilotinib remained the most frequently prescribed TKI (57.1%), followed by dasatinib (17.9%) and ponatinib (14.3%). Asciminib use was observed exclusively in later-line settings, accounting for 7.1% of 3L treatments, reflecting the recent incorporation of this novel therapeutic options into routine clinical practice. No patients received imatinib in the 3L setting. Among available records, deep molecular response (DMR; MR4 or better) was observed in 13.5%, 14.7%, and 7.1% of patients in 1L, 2L, and 3L, respectively, while major molecular response (MMR) without DMR was achieved by 7.5%, 9.2%, and 7.1%. An aggregated partial response category was documented in 14.9%, 15.5%, and 10.7%. No molecular response was documented for 60.9%, 56.3%, and 75.0% of patients across LoT. Conclusion This national RWE study describes contemporary TKI sequence in Brazil, with imatinib predominating in frontline therapy and second-generation TKIs commonly used after treatment changes. These findings support continued evidence generation on treatment sequence, molecular monitoring and outcomes in later-line CML management in Brazil. The use of later-generation agents, including ponatinib and asciminib, in 3L reflects an evolving therapeutic landscape for patients requiring multiple lines of therapy. Although molecular responses were documented across treatment lines, rates of DMR; MR4+ remained relatively low, even among patients receiving 1L therapy, suggesting potential opportunities to optimize treatment outcomes in routine clinical practice. Furthermore, missing molecular response data may limit the interpretation of response outcomes and highlights challenges in real-world data capture.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223147970