Treatment of chronic myeloid leukemia: assessing risk, monitoring response, and optimizing outcome
Naranie Shanmuganathan1,2,3,4, Devendra Keshaorao Hiwase1,2,3,4, David Morrall Ross1,2,3,4,5
1a Department of Haematology , Royal Adelaide Hospital , Adelaide , South Australia , Australia.
Abstract:
Over the past two decades, tyrosine kinase inhibitors have become the foundation of chronic myeloid leukemia (CML) treatment. The choice between imatinib and newer tyrosine kinase inhibitors (TKIs) needs to be balanced against the known toxicity and efficacy data for each drug, the therapeutic goal being to maximize molecular response assessed by BCR-ABL RQ-PCR assay. There is accumulating evidence that the early achievement of molecular targets is a strong predictor of superior long-term outcomes. Early response assessment provides the opportunity to intervene early with the aim of ensuring an optimal response. Failure to achieve milestones or loss of response can have diverse causes. We describe how clinical and laboratory monitoring can be used to ensure that each patient is achieving an optimal response and, in patients who do not reach optimal response milestones, how the monitoring results can be used to detect resistance and understand its origins.
Insights
Early monitoring of molecular response in chronic myeloid leukemia (CML) is crucial for treatment success. Timely assessment using BCR-ABL RQ-PCR helps optimize tyrosine kinase inhibitor (TKI) therapy and manage resistance.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Tyrosine kinase inhibitors (TKIs) are foundational treatments for chronic myeloid leukemia (CML).
- Balancing TKI efficacy and toxicity is key for optimal patient outcomes.
- Early molecular response predicts long-term CML treatment success.
Purpose of the Study:
- To outline strategies for monitoring molecular response in CML patients.
- To guide early intervention for suboptimal treatment responses.
- To identify causes of TKI resistance through monitoring.
Main Methods:
- Utilizing BCR-ABL RQ-PCR assays for molecular response assessment.
- Integrating clinical and laboratory data for comprehensive monitoring.
- Analyzing monitoring results to detect and understand resistance mechanisms.
Main Results:
- Early achievement of molecular targets strongly correlates with superior long-term outcomes.
- Monitoring facilitates timely intervention to ensure optimal patient response.
- Suboptimal responses can be addressed by understanding resistance origins.
Conclusions:
- Clinical and laboratory monitoring are essential for optimizing TKI therapy in CML.
- Early and consistent monitoring allows for proactive management of treatment response and resistance.
- Personalized CML treatment adjustments based on monitoring data improve patient outcomes.
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