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

Sep 30, 2026

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Retrospective cohort evidence evaluates low-dose dasatinib (50 mg daily) for adults with imatinib-resistant chronic phase chronic myeloid leukemia (CML-CP), emphasizing both treatment benefit and tolerability. The study analyzes 53 patients (2002–2025) using early and molecular response milestones (EMR, MMR, DMR) alongside progression-free survival and overall survival, and documents adverse events. Multivariate Cox modeling identifies predictors of poor response and progression, including T315I mutation, high ELTS risk, and elevated baseline BCR-ABL1. Clinically significant toxicity occurs in 49.1%, with frequent cytopenias and pleural effusion; dose-switching is required in a subset due to inadequate response or intolerance.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Introduction

Methods and Results

Molecular responses and survival

Adverse events and treatment switching

Conclusion

Cancer Reports ORIGINAL ARTICLE OPEN ACCESS 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 Nandhini Gangadaran | Harshal Mamlekar | Souvik Saha | Rajesh Kashyap | Sanjeev Yadav | Khaliqur Rahman | Ruchi Gupta | Mona Vijayaran | Manish Singh | Dinesh Chandra Department of Hematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India Correspondence: Rajesh Kashyap ([rajkashyapmd@gmail.com](rajkashyapmd@gmail.com)) | Sanjeev Yadav ([dr.sanjeev.ranchi@gmail.com](dr.sanjeev.ranchi@gmail.com)) Received: 21 May 2025 | Revised: 22 July 2025 | Accepted: 29 October 2025 Funding: The authors received no specific funding for this work. Keywords: BCR-ABL positive chronic myeloid leukemia | dasatinib | imatinib mesylate | pleural effusion | tyrosine kinase inhibitors ABSTRACT 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 (100mg daily), but is often limited by adverse events. Emerging evidence suggests low-dose dasatinib (50mg daily) may maintain efficacy with improved safety, but data in imatinibresistant 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 lowdose 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. 1 | Introduction Chronic myeloid leukemia (CML) is characterized by the presence of the Philadelphia chromosome t(9;22) (q34;q11), resulting in the formation of the BCR-ABL fusion gene, that drives the leukemic stem cell proliferation [1]. The incidence of CML is 1–2 cases per 100 000 adults [1], with a median age of diagnosis around 64 years [2]. Before the TKI (tyrosine kinase inhibitor) era, the treatment strategies included hydroxyurea, recombinant interferon-alfa (rIFN-α), and low-dose cytarabine. These therapies achieved hematologic responses in almost all of the patients, with limited complete cytogenetic responses (~14.5%), often accompanied by This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2026 The Author(s). Cancer Reports published by Wiley Periodicals LLC. Cancer Reports, 2026; 9:e70400 1 of 11 [https://doi.org/10.1002/cnr2.70400](https://doi.org/10.1002/cnr2.70400) significant toxicity [3]. Allogeneic hematopoietic cell transplantation (HCT), the only curative option, was limi

FAQs

What population and treatment dose were studied for imatinib-resistant CML-CP?

The study included 53 adults with imatinib-resistant CML-CP treated with low-dose dasatinib at 50 mg daily at a tertiary center.

Which biomarkers predicted poorer response and disease progression?

Multivariate analysis identified TKD mutations, with T315I mutation, high ELTS risk, and high baseline BCR-ABL1 as independent predictors of poor response.

What adverse events and tolerability outcomes were reported?

Clinically significant adverse events occurred in 49.1%, primarily cytopenias and pleural effusion; 22.6% required a TKI switch for inadequate response and 7.5% for intolerance.

Sep 30, 2026

Uploaded by Fahsai