# 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

## TL;DR

Low-dose dasatinib is effective and safer for treating chronic myeloid leukemia resistant to imatinib, with most patients achieving deep molecular responses.

## Contribution

Demonstrates the efficacy and safety of low-dose dasatinib in imatinib-resistant CML-CP and identifies biomarkers predicting treatment response.

## Key findings

- 41.5% of patients achieved MR4.5, and 20.8% achieved MR4.0 with low-dose dasatinib.
- T315I mutation, high ELTS risk, and high baseline BCR-ABL1 independently predicted poor response.
- 49.1% of patients experienced clinically significant adverse events, primarily cytopenias and pleural effusion.

## Abstract

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.

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.

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.

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.