Long‐term follow‐up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic‐phase chronic myeloid leukemia
Open accessAbstract
Background: Dasatinib, a potent Bcr‐Abl tyrosine kinase inhibitor, is approved for the treatment of chronic‐phase chronic myeloid leukemia (CML‐CP) in the frontline and salvage settings. Notable side effects include pleural effusions and myelosuppression. Dasatinib at 50 mg daily has previously been reported to be active and better tolerated than the approved 100‐mg daily dose. The aim of this study was to update the long‐term follow‐up results of dasatinib at 50 mg daily as frontline therapy for CML‐CP. Methods: Eighty‐three patients with newly diagnosed CML‐CP received dasatinib at 50 mg daily. Eligibility and response criteria were standards used in previous protocols. Results: After a minimum follow‐up of 12 months, 81 patients were evaluable. Two patients came off the study in less than 3 months. The rates of BCR‐ABL1 transcript levels (International Standard) at ≤10% and ≤1% at 3 months were 96% and 77%, respectively. The cumulative rates for a complete cytogenetic response by 6 and 12 months were 77% and 95%, respectively. The cumulative rates for a major molecular response, a molecular response with a 4.0‐log reduction, and a molecular response with a 4.5‐log reduction by 12 months were 81%, 55%, and 49%, respectively. Twenty‐one patients (25%) had treatment interruptions for a median of 13 days (range, 4‐64 days). Five patients (6%) developed pleural effusions; 4 of these patients (80%) required a dose reduction. Two patients (2%) failed to achieve any cytogenetic or molecular response and were taken off the study. At a median follow‐up of 24 months, none of the patients had disease transformation to an accelerated or blastic phase. The 2‐year event‐free and overall survival rates were 100%. Conclusions: These updated results continue to support 50 mg of dasatinib daily as an effective and safe dose for early CML‐CP.
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Intermittent hit-and-run senolytic dosing could reduce side effects of D that generally appear after weeks to months of continuous administration.
“This intermittent ‘hit-and-run’ strategy of senolytic administration could serve to reduce side effects of agents such as D, which generally appear after weeks to months of continuous administration118,119.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [118]
The Results (Safety; page unavailable) document adverse effects during daily dasatinib treatment, including pleural effusions and treatment interruptions. The paper does not establish that these effects generally begin after weeks to months, or test whether intermittent senolytic dosing reduces them; its regimen was daily dosing. (LLM, conf=0.82)
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Cellular senescence and senolytics: the path to the clinic
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- Authors
- Naqvi, K., Jabbour, E., Skinner, J., Anderson, K., Dellasala, S., Yilmaz, M., Ferrajoli, A., Bose, P., Thompson, P., Alvarado, Y., Jain, N., Takahashi, K., Burger, J., Estrov, Z., Borthakur, G., Pemmaraju, N., Paul, S., Cortes, J., & Kantarjian, H. M.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- The University of Texas MD Anderson Cancer Center Houston Texas
- Corresponding author
- Kantarjian, Hagop M.
- ORCID
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2019-09-25
- Volume
- 126
- Issue
- 1
- Pages
- 67-75
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- PMC
- PMC8529949
- OpenAlex
- W2977193627
- Cited by
- 135
- References
- 28
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 21 · 2023: 22 · 2022: 27 · 2021: 23 · 2020: 16
- FWCI
- 11.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Texas MD Anderson Cancer Center (CA100632)
- Topics
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- dasatinib, chronic phase CML, first-line therapy, BCR-ABL tyrosine kinase inhibitors, molecular response, complete cytogenetic response, pleural effusion, myelosuppression, event-free survival, overall survival, disease transformation
- MeSH terms
- Imatinib Mesylate, Dasatinib, Adult, Aged, Aged, 80 and over, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Male, Middle Aged, Sulfonamides, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Chronic-Phase, Fusion Proteins, bcr-abl, Treatment Outcome, Disease-Free Survival, Bridged Bicyclo Compounds, Heterocyclic, Protein Kinase Inhibitors
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