Asciminib

How it works

It is a first-in-class allosteric inhibitor that binds the myristoyl pocket of BCR-ABL1, locking the kinase in an inactive conformation rather than competing at the ATP site.

Prescribing in practice

• It can cause myelosuppression with thrombocytopenia and neutropenia that may predispose to bleeding and infection, requiring blood-count monitoring and dose modification.
• Pancreatic toxicity, raised lipase/amylase and pancreatitis can occur, so symptoms and enzymes are monitored.
• It is metabolised via CYP3A4 and interacts with several drugs, so concurrent medicines and the SPC interaction list should be reviewed.

Monitoring

Monitor full blood count, pancreatic enzymes and BCR-ABL1 transcript response, with periodic checks of ECG/QT and metabolic parameters.

Counselling the patient

• Report unusual bruising, bleeding, fever or severe abdominal pain.
• Take consistently in relation to food as directed and avoid grapefruit.

Evidence & guidelines

Approval is based on randomised and single-arm trials showing superior molecular response versus comparator tyrosine kinase inhibitors in pretreated chronic-phase disease.