PBS Criteria Expanded for Acalabrutinib

The Pharmaceutical Benefits Scheme (PBS) listing for acalabrutinib has been expanded to include the first-line treatment of chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) in combination with venetoclax. Patients receive acalabrutinib monotherapy for the first two cycles, followed by combination therapy with venetoclax from cycle three.

Acalabrutinib is a second-generation Bruton’s tyrosine kinase (BTK) inhibitor. In B-cells, BTK signalling drives B-cell proliferation, trafficking, chemotaxis, and adhesion. Venetoclax is a selective inhibitor of B-cell lymphoma-2 (BCL-2), a protein that regulates apoptosis and is often overexpressed in CLL and SLL.

Both acalabrutinib and venetoclax are administered orally with a fixed dosing period of 14 cycles for this indication (where each cycle is 28 days). Acalabrutinib is taken twice daily, while venetoclax is taken daily from cycle three. A five-week ramp-up schedule is employed for venetoclax to gradually reduce tumour burden and lower the risk of tumour lysis syndrome.

The AMPLIFY trial was conducted in patients with untreated CLL. Combination therapy with acalabrutinib and venetoclax was associated with significantly prolonged progression-free survival compared with chemoimmunotherapy. Common adverse events included infection, neutropenia, and haemorrhage. Acalabrutinib has a more favourable cardiovascular safety profile than first-generation BTK inhibitors such as ibrutinib; however, hypertension and atrial fibrillation can still occur.