1 Recommendations

1 Recommendations

1.1 Venetoclax plus obinutuzumab 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 companies provide the drugs according to the commercial arrangements.

1.2 Venetoclax plus obinutuzumab is recommended for use within the Cancer Drugs Fund as an option for untreated CLL in adults, only if:

  • there is no 17p deletion or TP53 mutation, and FCR or BR is suitable, and

  • the conditions in the managed access agreement for venetoclax plus obinutuzumab are followed.

1.3 These recommendations are not intended to affect treatment with venetoclax plus obinutuzumab 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

People with untreated CLL are offered different treatments depending on whether they are likely to tolerate chemo-immunotherapy, and whether they have certain genetic abnormalities (such as a 17p deletion or TP53 mutation). In people with a 17p deletion or TP53 mutation, CLL does not usually respond well to standard chemo-immunotherapy, and ibrutinib is usually used. In people without a 17p deletion or TP53 mutation, FCR or BR are the most common chemo-immunotherapies used. If FCR or BR is unsuitable, obinutuzumab plus chlorambucil is used instead.

Venetoclax plus obinutuzumab has not been directly compared with ibrutinib in people with a 17p deletion or TP53 mutation, and the results of an indirect comparison are uncertain. The cost-effectiveness estimates suggest that venetoclax plus obinutuzumab is less effective but less costly than ibrutinib. These estimates are within what NICE normally considers an acceptable use of NHS resources, so it is recommended for routine use in the NHS for these people.

Clinical trial evidence shows that, in people without a 17p deletion or TP53 mutation and for whom FCR or BR is unsuitable, CLL treated with venetoclax plus obinutuzumab takes longer to progress than CLL treated with obinutuzumab plus chlorambucil. The cost-effectiveness estimates suggest that venetoclax plus obinutuzumab is more effective and less costly than obinutuzumab plus chlorambucil. Therefore, venetoclax plus obinutuzumab is recommended for routine use in the NHS for these people.

Venetoclax plus obinutuzumab has not been directly compared with FCR or BR in people without a 17p deletion or TP53 mutation and for whom these treatments are suitable. The results of an indirect comparison are uncertain. Also, some of the cost-effectiveness estimates are higher than the range NICE normally considers an acceptable use of NHS resources. Therefore, venetoclax plus obinutuzumab cannot be recommended for routine use in the NHS for these people.

An ongoing clinical trial is directly comparing venetoclax plus obinutuzumab with FCR and BR in people with untreated CLL without a 17p deletion or TP53 mutation for whom these treatments are suitable. Data from this trial could help address the uncertainty about the clinical effectiveness of venetoclax plus obinutuzumab in this population. Venetoclax plus obinutuzumab has the potential to be a cost-effective use of NHS resources. Therefore, it is recommended for use in the Cancer Drugs Fund for these people while the data from the trial are collected.

  • National Institute for Health and Care Excellence (NICE)