It is important to assess for the reason why the patient is not responding well to treatment. They may be resistant to TKIs, they may not be adhering to treatment for various reasons, or they may be experiencing drug interactions (Hochhaus et al. 2017).

Patients with treatment failure should have a bone marrow examination to determine/confirm the CML phase and document clonal cytogenetic changes. CML cells should be tested for their BCR–ABL1 mutational profile to help select an appropriate TKI (Hochhaus et al. 2017).

Mutational analysis is recommended for patients who:

• develop accelerated or blast phase CML
• experience treatment failure on their current TKI therapy.

According to the European LeukemiaNet 2020 guidelines (Hochhaus et al. 2020), mutations account for about a third of treatment-resistant cases in patients in the chronic phase and about two-thirds of treatment-resistant cases in patients in accelerated or blast phase.

Managing patients who are not achieving optimal response is complex. Each patient should be evaluated to determine if referral to a multidisciplinary team is necessary. From the time of diagnosis, the team should offer patients appropriate psychosocial care, supportive care, advance care planning and symptom-related interventions as part of their routine care. The approach should be personalised to meet the patient’s individual needs, values and preferences. The full complement of supportive care measures as described throughout the optimal care pathway and in Appendices A, B and C should be offered to assist patients and their families and carers to cope. These measures should be updated as the patient’s circumstances change.