Acalabrutinib to become a treatment option for certain groups of CLL patients in England

Acalabrutinib will be available to CLL patients in the following groups:

• previously treated CLL patients.
• Untreated patients with 17p deletion or TP53 mutations. These are genetic mutations that affect how well current treatments, such as FCR, work.
• Untreated patients who are unsuitable for current treatments, such as FCR, for other reasons. For example, some patients are too unwell to have strong chemotherapy-based treatments or have other health conditions that mean chemotherapy would make them very unwell, and so need to have alternative options for treatment.

In recent years, the number of CLL treatments available has increased significantly, with venetoclax and ibrutinib being approved and widely used. However, during this appraisal, Leukaemia Care and the clinical experts argued that more options for patients are always important, so patients can discuss with their doctor the therapy that is right for them. Venetoclax and ibrutinib, whilst highly effective treatments, come with side effects that also mean they are not suitable for all. For example, ibrutinib can cause serious heart issues and is rarely suitable for those with existing heart issues.

The two groups of patients who are eligible for acalabrutinib for their first treatment have a smaller pool of treatment options available to them, due to the genetic mutations or other health conditions. Acalabrutinib helps to

Acalabrutinib was not assessed in the population of patients who are eligible to have chemotherapy first line. The pharmaceutical company, AstraZeneca, did not submit evidence to NICE to have this

Acalabrutinib is currently also being assessed by the Scottish Medicines Consortium (SMC) for use in Scotland. We will report on the outcome of this assessment when it has finished.

Whilst FCR is a treatment that is highly effective, it comes with side effects, some of which are long term, that many patients would like to avoid. Therefore, Leukaemia Care, along with other patient groups, argued that there is still an unmet need in the population of patients who would otherwise be treated with FCR.

Leukaemia Care will continue to work closely with AstraZeneca and NICE to work towards greater access to therapies for patients.

Acalabrutinib in a Bruton’s tyrosine kinase (BTK) inhibitor (often shortened to BTKi). BTK is a protein that is active in B cells, the type of immune cell that becomes cancerous in CLL. Normally the protein relays signals from outside the cell to as series of other proteins, ultimately causing the B cells to divide. However, in CLL, the BTK protein is mutated and always switched on, rather than needing to be switched on by an outside signal. This means the B cells divide when they are immature, creating too many underdeveloped cells that do not work properly (these are the CLL cells). A BTK inhibitor stops the BTK protein from working, therefore stopping too many cells from being made and allowing the remaining cells to correctly develop.

Importantly, acalabrutinib inhibits the BTK protein in a different way to other BTKi drugs used, ibrutinib and idealisib. This means that it can work for those who have previously had these other BTK inhibitors, opening up more treatment options for patients who have tried all other treatments.

As part of our submission to NICE, Leukaemia Care presented the results of a survey of patients who had taken acalabrutinib. 40 people who had been treated with acalabrutinib took part and overall reported a good experience with the treatment. For example, 68% of patients said that acalabrutinib managed all their symptoms, with 45% reported a reduction in fatigue and 82% a reduction in their lymph nodes.

Side effects of treatment are also important; 36% of patients had no side effects, 25% said they did have side effect but these had no impact on their life, and 23% said the side effects had only a small impact on their life.

The main trial evidence came from the ELEVATE clinical trial, which compared acalabrutinib (sometimes given with obinutuzumab) with a combination of chlorambucil and obintizumab. This trial showed a significant improvement in progression-free survival (i.e. an increase in the length of time people survive without their CLL getting worse) in patients who took acalabrutinib, compared with those who had the chlorambucil instead. Chlorambucil is still used in some patients who cannot have FCR, so this trial showed that acalabrutinib would be an effective option for these patients.

Many patients who were being considered as potential groups to be offered acalabrutinib would usually be offered ibrutinib as their alternative treatment. Whilst there is currently no trial evidence for a direct comparison between acalabrutinib and ibrutinib, a comparison between acalabrutinib and a different BTKi, idealisib, was available from the ASCEND trial. Additionally, NICE were able to look at the effectiveness of ibrutinib in patients in another trial, RESONATE. Trials that directly compare treatments options are the best type of evidence to use but are not always available. NICE concluded that the various trials were appropriate to allow NICE to make a decision about the effectiveness of acalabrutinib compared to ibrutinib.

As well as acalabrutinib being shown to be as effective or more effective than alternatives, evidence during the process suggested that acalabrutinib is likely to be cost saving compared to using ibrutinib, which is a positive for the NHS. However, this does not mean other treatments will not be available to patients; all approved options remain available and clinicians and patients are able to choose the treatment that works best for them.