Current status and novel strategy of CML
1Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 428, Houston, TX, 77030, USA.
Abstract:
The advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achievement of durable deep molecular remission. Therefore, the second-generation TKIs should be considered as initial therapy for chronic-phase CML. Switch of therapy is warranted in case of treatment failure, including resistance and/or intolerance. The life expectancy of patients with CML is approaching that of the general population. Given an expected lifespan, future perspectives should consider the strategy for the optimal choice of TKIs, allowing for long-duration of effective TKI therapy with less toxicity to aim for a functional cure. A novel prediction approach such as artificial intelligence-driven analysis on the accumulated data from clinical trials paves a promising path for the personalized recommendation on frontline TKIs and precise survival prediction.
Insights
Second-generation tyrosine kinase inhibitors (TKIs) offer faster, deeper molecular responses in chronic myeloid leukemia (CML) and are recommended for frontline therapy. Achieving durable remission is key for potential treatment discontinuation and functional cure.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Tyrosine kinase inhibitors (TKIs) have transformed chronic myeloid leukemia (CML) treatment outcomes.
- Four TKIs are available for frontline therapy: imatinib (first-generation) and dasatinib, nilotinib, bosutinib (second-generation).
Purpose of the Study:
- To evaluate the role of second-generation TKIs in achieving deep molecular remission for potential CML treatment discontinuation.
- To discuss optimal TKI selection strategies for long-term therapy and functional cure in CML patients.
Main Methods:
- Review of current TKI treatment guidelines and clinical trial data for chronic-phase CML.
- Analysis of molecular response rates, survival benefits, and toxicity profiles of different TKIs.
Main Results:
- Second-generation TKIs induce faster and deeper molecular responses than imatinib, though without a significant survival advantage.
- Durable deep molecular remission is essential for treatment discontinuation and functional cure in CML.
Conclusions:
- Second-generation TKIs are recommended for initial therapy in chronic-phase CML to achieve necessary remission depth.
- Future strategies should focus on personalized TKI selection for long-term efficacy, reduced toxicity, and functional cure, potentially aided by AI-driven predictions.
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