When managing people with CML who have treatment failure or resistance, treatment will depend on the degree and timing of failure, mutation analysis, age, comorbidities and adherence and toxicity to prior TKIs. Note that poor compliance with TKI therapy is the most common reason for treatment failure.

Treatment may include:

• second-line treatment with a second- or third-generation TKI
• third-line treatment with an alternative TKI such as ponatinib or asciminib, or an allogeneic stem cell transplant
• allogeneic stem cell transplantation for eligible patients who no longer have an effective TKI option or for those with blast phase disease who have achieved a second chronic phase.

The potential goals of treatment should be discussed, respecting the patient’s cultural values. Wherever possible, written information should be provided.

Encourage early referral to clinical trials or accepting an invitation to participate in research.