1 Recommendations

1.1 Acalabrutinib as monotherapy is recommended as an option for untreated chronic lymphocytic leukaemia (CLL) in adults, only if:

there is a 17p deletion or TP53 mutation, or
there is no 17p deletion or TP53 mutation, and fludarabine plus cyclophosphamide and rituximab (FCR), or bendamustine plus rituximab (BR) is unsuitable, and
the company provides the drug according to the commercial arrangement.

1.2 Acalabrutinib as monotherapy is recommended, within its marketing authorisation, as an option for previously treated CLL in adults. It is recommended only if the company provides the drug according to the commercial arrangement.

1.3 These recommendations are not intended to affect treatment with acalabrutinib that was started in the NHS before this guidance was published. People having treatment outside these recommendations may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.

Why the committee made these recommendations

This appraisal looks at the use of acalabrutinib as monotherapy. NICE has not made recommendations on the use of acalabrutinib with obinutuzumab because the company did not submit any data for this combination.

People with untreated CLL that has a 17p deletion or TP53 mutation usually have ibrutinib. For this group, acalabrutinib has not been directly compared with ibrutinib in a clinical trial, and the results of an indirect comparison are uncertain. The company assumed that acalabrutinib is as effective as ibrutinib in a cost‑minimisation analysis. Despite the uncertainties, acalabrutinib is likely to be cost saving compared with ibrutinib. Therefore, acalabrutinib is recommended in this group.

People with untreated CLL without a 17p deletion or TP53 mutation usually have FCR or BR. If FCR or BR is unsuitable, chlorambucil plus obinutuzumab is offered instead. Clinical trial evidence in this group shows that CLL takes longer to progress when treated with acalabrutinib compared with chlorambucil plus obinutuzumab. However, the overall survival benefit is uncertain. The cost-effectiveness estimates are within what NICE normally considers an acceptable use of NHS resources, so acalabrutinib is recommended in this group.

People with previously treated CLL that has relapsed or does not respond to treatment, usually have ibrutinib or venetoclax plus rituximab. For this group, acalabrutinib has not been directly compared with ibrutinib or with venetoclax plus rituximab. The results of an indirect comparison with ibrutinib are uncertain. The company assumed that acalabrutinib was as effective as ibrutinib in the cost‑minimisation analyses. Despite the uncertainty, acalabrutinib is likely to be cost saving compared with ibrutinib. Therefore, acalabrutinib is recommended in this group.