[Key points in second-line therapy for chronic myeloid leukemia]

Area of Science:

• Oncology
• Hematology
• Pharmacology

Background:

• Tyrosine kinase inhibitors (TKIs) have transformed chronic myeloid leukemia (CML) treatment.
• New agents like asciminib expand first-line therapy options in Japan.
• A significant percentage of patients require second-line treatment due to resistance or intolerance.

Purpose of the Study:

• To provide guidance on selecting optimal second-line TKI therapy for CML.
• To address the complexities arising from diverse first-line TKI choices.
• To review key considerations for managing second-line TKIs, including asciminib and ponatinib.

Main Methods:

• Review of current clinical guidelines and evidence for second-line TKI selection in CML.
• Analysis of factors influencing treatment decisions, including adverse event profiles and mutation status.
• Assessment of TKI efficacy and safety data in second-line and later settings.

Main Results:

• Switching to second-line therapy requires careful consideration of the reason for discontinuation (intolerance vs. resistance).
• Intolerance management involves assessing adverse event profiles and potential cross-intolerance.
• Resistance necessitates BCR::ABL1 mutation assessment to guide the selection of mutation-sensitive second-line TKIs.

Conclusions:

• Optimal second-line TKI selection in CML is crucial due to increasing first-line options.
• Personalized treatment strategies, considering mutation profiles and TKI characteristics, are essential.
• Further evidence supports the use of asciminib and ponatinib in later treatment lines.