Dose Modifications in the Management of Chronic Phase Chronic Myeloid Leukemia: Who, What, and When
Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA
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Department of Pharmacy, University of Washington Medicine, Seattle, WA
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Department of Pharmacy, University of Washington Medicine, Seattle, WA
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Department of Pharmacy, University of Washington Medicine, Seattle, WA
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Harvard Medical School, Boston, MA
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With the availability of BCR::ABL1 targeted tyrosine kinase inhibitors (TKIs), outcomes for most individuals with chronic phase chronic myeloid leukemia (CP-CML) are outstanding, with life expectancy similar to age-matched peers. Treatment-emergent adverse events (TEAEs) impair quality of life and many patients struggle with low-level chronic AEs, which for some individuals impact emotional well-being as well as social and work functioning. An emerging body of data supports that many TEAEs are related to therapy dose and can improve with dose reduction. However, it is critical that dose reductions do not alter current outcomes, especially in the rare patients who are at greater risk of losing response or transforming to acute leukemia. Organizations including the National Comprehensive Cancer Network have begun to address when dose reductions may be considered in patients with CP-CML. In this manuscript, we review retrospective and prospective data reporting outcomes in patients after dose reduction and review data supporting lower dose preemptive dosing in first-line and later-line therapy. Switching therapy for intolerance can result in improvements in symptoms and limit toxicity, but other TEAEs may occur. Additionally, emerging therapeutics such as the new class of BCR::ABL1 allosteric inhibitors are under evaluation with a goal of improving tolerability. However, with many TKIs on the cusp of becoming generic, dose reduction becomes an appealing and important cost-effective strategy to minimize TEAEs and improve quality of life while preserving outstanding outcomes in CP-CML.
Submitted December 13, 2023; final revision received May 22, 2024; accepted for publication June 4, 2024.
Disclosures: Dr. Oehler has disclosed receiving grant/research support for Novartis, Ascentage Pharma, Terns Pharmaceuticals, Pfizer, and Shenzhen TargetRx; and serving as a consultant for Novartis, Terns Pharmaceuticals, and Ascentage Pharma. Dr. Hobbs has disclosed serving as a scientific advisor for Novartis, Bristol Myers Squibb, GSK, Incyte, and Pfizer; and serving as a consultant for PharmaEssentia. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.
Supplementary material: Supplementary material associated with this article is available online at https://doi.org/10.6004/jnccn.2024.7044. The supplementary material has been supplied by the author(s) and appears in its originally submitted form. It has not been edited or vetted by JNCCN. All contents and opinions are solely those of the author. Any comments or questions related to the supplementary materials should be directed to the corresponding author.
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