Long-term outcomes of tyrosine kinase inhibitors in chronic myeloid leukemia: reflections on a quarter century of TKIs in CML : review series
Long-term outcomes with tyrosine kinase inhibitors (TKIs) show that their impact on chronic myeloid leukemia (CML) is sustained as shown by 13 studies with 5- to 14-year-follow-up, and numerous shorter-term studies of newly diagnosed chronic-phase CML. Twenty-five years of imatinib (IM) treatment co...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
27 February 2025
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| In: |
Blood
Year: 2025, Volume: 145, Issue: 9, Pages: 910-920 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood.2024026311 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood.2024026311 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006497124108828 
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| Author Notes: | François Guilhot and Rüdiger Hehlmann |
MARC
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| 520 | |a Long-term outcomes with tyrosine kinase inhibitors (TKIs) show that their impact on chronic myeloid leukemia (CML) is sustained as shown by 13 studies with 5- to 14-year-follow-up, and numerous shorter-term studies of newly diagnosed chronic-phase CML. Twenty-five years of imatinib (IM) treatment confirm its beneficial effect on survival and possible cure of CML. Large, randomized, academic, treatment-optimization studies have confirmed and extended the pivotal International Randomized Study on Interferon and STI571. The 3 academic trials in Germany, France, and the United Kingdom did not show benefit of the IM-interferon (IFN) combination, despite the immunomodulatory properties of IFN. Second-generation (2G) TKIs induce responses faster than IM and recognize IM-resistance mutations but do not prolong survival compared with IM. Adverse drug-related reactions (ADRs) limit the general use of 2GTKIs despite frequent but mostly mild IM-ADRs. Molecular monitoring of treatment efficacy has been established serving as an example for other neoplasms. Comorbidities, transcript type, and the negative impact of high-risk additional chromosomal abnormalities were addressed. A new prognostic score (European Treatment and Outcome Study long-term survival score) accounts for the fact that the majority of patients with CML die of other causes. Non-CML determinants of survival have been identified. Large and long-term observational studies demonstrate that progress with CML management has also reached routine care in most but not all instances. Despite merits of 2GTKIs, IM remains the preferred treatment option for CML because of its efficacy and superior safety. | ||
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