Reconsidering Later-Line Therapies in CML Management

EP: 1.NCCN Guidelines and Early Response Monitoring in Chronic Myeloid Leukemia

EP: 2.Shifting Therapeutic Urgency and TKI Strategy

EP: 3.Leveraging Trial Data to Guide Frontline TKI Use

EP: 4.Milestones That Matter: Using Molecular and Clinical Benchmarks to Guide CML Therapy

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EP: 5.Reconsidering Later-Line Therapies in CML Management

EP: 6.The Pharmacist’s Role in Navigating Toxicity With TKIs

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Ponatinib has traditionally been reserved for later-line chronic myeloid leukemia (CML) therapy due to concerning long-term toxicities, including cardiac dysfunction and vascular thrombotic events, limiting its use to carefully selected patients. However, both ponatinib and asciminib possess unique capabilities to overcome the challenging T315I mutation, making them valuable therapeutic options for resistant CML cases. The availability of these advanced tyrosine kinase inhibitors (TKIs) provides clinicians with powerful tools for managing complex cases while requiring careful patient selection and monitoring protocols.

Recent clinical evidence, particularly from the ASC4FIRST trial, has expanded the role of advanced TKIs such as asciminib into frontline CML treatment settings. This shift represents a significant advancement in CML management, offering patients access to highly effective therapies earlier in their treatment journey. The approval of asciminib for frontline use provides clinicians with additional treatment options that combine superior efficacy with improved tolerability profiles compared with traditional first-line agents.

Modern CML treatment strategies increasingly consider using advanced TKIs earlier in the treatment sequence, particularly for patients who may not be candidates for other second-generation TKIs due to comorbidities or specific mutation profiles. This strategic approach allows clinicians to preserve highly effective agents such as ponatinib for patients with T315I mutations while using asciminib’s favorable profile for broader patient populations. The evolution toward earlier use of advanced TKIs represents a paradigm shift in CML management, prioritizing both efficacy and tolerability from treatment initiation.