Real-World Outcomes With Low-Dose Dasatinib (50 mg) in Imatinib-Resistant Chronic Myeloid Leukemia in Chronic Phase: A Retrospective Analysis of Efficacy and Safety.

BACKGROUND: Dasatinib, a potent second-generation tyrosine kinase inhibitor (TKI), is highly effective in chronic myeloid leukemia in chronic phase (CML-CP) resistant to imatinib at standard dosing (100 mg daily), but is often limited by adverse events. Emerging evidence suggests low-dose dasatinib (50 mg daily) may maintain efficacy with improved safety, but data in imatinib-resistant CML-CP remain limited. AIMS: To evaluate the efficacy and safety of low-dose dasatinib (50 mg daily) in patients with imatinib-resistant CML-CP and to identify predictors of treatment response and disease progression. METHODS AND RESULTS: This retrospective cohort study included 53 adults with imatinib-resistant CML-CP treated with low-dose dasatinib at a tertiary center in Northern India (2002-2025). Early molecular response (EMR), major molecular response (MMR), deep molecular response (DMR), progression-free survival (PFS), overall survival (OS), and adverse events were assessed. Multivariate Cox regression identified predictors of poor response and disease progression. Among 53 patients (median age 50 years), 41.5% achieved MR4.5, 20.8% MR4.0, and 15.1% MMR without DMR. Prior loss of MMR on imatinib significantly correlated with a superior response to dasatinib (p = 0.002). TKD mutations were present in 32.1%; the T315I mutation, high ELTS risk, and baseline BCR-ABL1 ⟩ 100% independently predicted poor response. Clinically significant adverse events occurred in 49.1%, primarily cytopenias and pleural effusion. Among our cohort, 22.6% required a TKI switch due to inadequate response and 7.5% due to intolerance. CONCLUSION: Low-dose dasatinib is effective and tolerable in imatinib-resistant CML-CP, with nearly two-thirds achieving DMRs. Predictive biomarkers (T315I mutation, high ELTS risk, high baseline BCR-ABL1) can guide dose optimization.