New treatment option for AML patients approved in England, thanks to campaign by Leukaemia Care

The role of NICE in England is to decide if a treatment is cost-effective for use on the NHS. They do this by comparing the treatment to existing treatments, if there are any. The process involves looking at clinical trial data and information on the cost of delivering the new drug. A committee of people at NICE then makes a recommendation based on the evidence they have.

Leukaemia Care provided a submission which outlined the value of this treatment to patients. We were asked to provide evidence of the need for the treatment by discussing the limitation of the current treatments for AML. We were also asked what the advantages and disadvantages are of the combination of venetoclax with azacitidine.

We provided this information from surveys of the patient’s community, such as the “Living with Leukaemia” survey conducted by Leukaemia Care, as well as our knowledge on patient outcomes when they are treated with different treatments in clincal trials. If you are ineligible for intensive chemotherapy when you are diagnosed with acute myeloid leukaemia, there can be a few reasons for this. A common reason is that some people are too unwell for intensive treatment, with the leukaemia or due to other illness they have, and intensive treatment could harm them more than help them. We know from clinical trials and from real world studies that outcomes for patients who must have less intensive chemotherapy are poor and some people choose not to have treatment at all. Therefore, there is a big unmet need for treatments that are effective in this groups of patients.

Our surveys confirmed that patient agreed that there are not enough treatment options for this group of patients. Additionally, our data shows that as people get older, the number of people who wish to be cured of their illness does decrease, it doesn’t go right down to 0%. There are a significant number of patients over the age of 75 that are still interested in treatments that could give them both longer life and better quality of life.

As well as the treatment being effective for these patients, venetoclax with azacitidine can often be given at home as a treatment. Our surveys show that patients would prefer a treatment than avoids being an inpatient as much as possible, and we also know that travel costs are one of the biggest extra costs that come from a diagnosis of leukaemia. Therefore, we explained to the committee that this treatment would be welcomed by patients for this reason too and the clinical experts also agreed.

Leukaemia Care also invited a patient who had experience of treatment to provide a submission to the committee, reiterating that their experience with venetoclax and azacitidine was largely positive and that they would not have had many treatment options left at all without it. They said about the treatment: “I took that option because I could be at home with my children and I was told that it was less toxic than the chemotherapy… There are many benefits to this drug, firstly it seems to be very swift and effective. The patient can stay at home and self-administer and carry out most normal activities. Whilst I decided not to return to work until treatment had finished, I felt that I could have managed a partial return.”

Acute myeloid leukaemia (AML) is a type of leukaemia that develops rapidly and is life threatening if not treated quickly. The usual treatment is with intensive chemotherapy, which works by killing as many cells as possible, often some healthy ones along with the leukaemia cells. The killing of healthy cells is the cause of many side effects that often come with these treatments, so the rest of the body must be healthy enough to withstand this damage, and this is the reason why the chemotherapy is described as intensive.

Venetoclax is an oral BCL-2 inhibitor. The BCL-2 protein prevents programmed cell death and thereby supports the survival of leukaemia cells. Venetoclax inhibits and blocks this activity of the BCL-2 protein, causing cell death of the leukaemia cells. It is also used to treat another type of leukaemia called chronic lymphocytic leukaemia (CLL).

The usual treatment for people who can’t have intensive chemotherapy is milder types of chemotherapy called hypomethylating agents. These drugs work by preventing a chemical reaction called methylation happening to DNA. When DNA cannot be methylated, it is a sign to the cell that the DNA must be destroyed. This in turn triggers the leukaemia cell to die too.

Two types of hypomethylating agents used for AML are azacitidine and cytarabine; which one patients would have would depend on the amount of leukaemia cells in their body at the time of treatment. However, neither of them are effective for very long and still bring some side effects. The combination of venetoclax with azacitidine has been shown to work better (see next section). Venetoclax is also being looked at in combination with cytarabine, but this assessment is still ongoing.

As well as evidence from Leukaemia Care on the impact of this treatment on quality of life, clinical trial data was examined by NICE to understand the treatment. The key clinical trial for the combination of venetoclax and azacitidine was VIALE-A, where it was compared to people who were receiving just azacitidine.

The trial showed the combination of venetoclax and azacitidine did increase the survival of patients compared to those who had just had azacitidine. However, one challenge was that the committee were uncertain as to whether the treatment had the potential to cure patients in the long term. The pharmaceutical company presented evidence to show that a proportion of people were cured, and the committee and the clinical experts present agreed that a proportion would be, but it is not clear how many. Despite this uncertainty about whether or not venetoclax and azacitidine can cure people, the committee agreed the treatment was beneficial and cost-effective, so were able to make it available.