The brand name for this treatment is Blincyto© and it is manufactured by Amgen.
The National Institute of Health and Care Excellence (NICE), who make decisions about which treatments to fund for use on the NHS in England, made a similar, but not identical, decision to approve blinatumomab in June 2019. However, NICE only approved the use of blinatumomab in the first remission (i.e. in patients who have only tried one other treatment).
The SMC today has approved the use of blinatumomab for patients in first or second remission (i.e. have tried up to two treatments before blinatumomab). The SMC’s decision today means that, whilst there has been a delay of around eight months between approval for use in England and approval in Scotland, Scottish patients have access to blinatumomab at more stages of treatment, meaning they can try other treatments first should they wish.
Blinatumomab has previously been approved by NICE and the SMC in 2017 for use in ALL patients who have fully relapsed and is often used to control disease before the patient has a stem cell transplant. However, this was a proposal to use the drug in a different population of patients.
What is blinatumomab?
Blinatumomab is a type of drug called immunotherapy, which means it is designed to help the patient’s immune system fight the cancer. More precisely, blinatumomab is a bi-specific T-cell engager (BiTE). This means that it picks up cancer cells and joins them to T-cells, which are a type of immune system cell that can kill cancer. By bringing the T-cells closer to the cancer cells, the T-cells have a better chance of killing cancer cells than if they simply met the cancer cells by chance in the blood.
Therefore, blinatumomab relies on certain things being right in the patient’s body in order to work. Patients must be CD19 positive, as this is the part of the cancer cells that blinatumomab attaches itself too. Blinatumomab only works on patients whose cancer is in their B-cells (another immune system cell), because working T-cells are essential to how the drug works. Some patients have T-cell ALL, which means their T-cells are the cancerous cells and blinatumomab would not work here.
Why have the SMC and NICE each approved blinatumomab twice?
A drug is approved by the SMC and NICE separately per indication. An indication is the precise group of patients that the manufacturer proposed that the drug be used in. An indication is usually based on the type of patients that clinical trials were conducted on. The SMC and NICE examine the evidence for each proposed indication separately, to ensure there is evidence that the drug works in each group of patients; it wouldn’t be safe to assume that because a drug works for one group, it will automatically work in another.
Blinatumomab is already approved for use in the indication of “ALL patients who have relapsed/are refractory”. In this instance, the manufacturer has asked SMC (and NICE in 2019) to decide if blinatumomab will also work for the indication of patients that haven’t relapsed fully yet, but are more likely do so because they have measurable residual disease.
What is MRD?
Minimal, or measurable, residual disease is a concept where patients are technically in remission, but they still have some leukaemia cells present in their body. Remission is traditionally defined by the moment when no leukaemia cells can be found under the microscope. However, the use of a microscope is not very precise. In recent years, researchers have found a number of markers on leukaemia cells, or within their genes, that they can use to find leukaemia cells that might be missed under the microscope.
Being MRD positive means that cells have been found in the patient with the markers, even if you can’t see these cells with a microscope yet. Being MRD negative or undetectable is when cells with these markers can’t be found at all, with a microscope nor with more precise techniques.
The problem with MRD testing is that it is new and not everyone uses the same techniques to check a patient’s MRD status, and some clinics don’t even test for it at all. The most common technique is flow cytometry, but there are techniques that are less widely available but are able to find more cells; one example is next generation sequencing.
Find out more about MRD here.
What is the significance of MRD for this decision?
It has been shown that the fewer leukaemia cells that patients have in their blood or bone marrow, the less likely the patient is to relapse. However, as MRD testing is a new concept and still needs to be implemented more widely and accurately, there was much debate as to whether it should be used to define a population of patients.
Leukaemia Care, along with leading ALL clinicians, participated in SMC meetings to explain and debate the importance of MRD as a prognostic factor (i.e. the number of cells in a patient’s body predicts their likelihood of relapse) and hence argue for this population of patients to have access to the treatment.
The fact that patients who are MRD positive can have blinatumomab is also important for the chance of being cured. This is because their MRD status before transplant predicts the likelihood of the transplant being a success. If a patient is MRD positive after chemotherapy, this allows them to have blinatumomab, reach MRD negative or undetectable, and then go into a transplant with a much better outlook than if they didn’t have the blinatumomab at all.
Given that blinatumomab can already be used once a patient has officially relapsed, it was important that patients should be given a chance to have blinatumomab earlier, while they are MRD positive (and so very likely to relapse) but can avoid the stress and possibly physical pain of a full relapse or unsuccessful transplant. In the words of a leading clinician, the NHS must “pay now or pay later”.
Charlotte Martin, Patient Advocacy Manager at Leukaemia Care, said, “A diagnosis of acute lymphoblastic leukaemia can have a huge emotional impact on the lives of patients, as well as their family and friends.
“We welcome the decision to recommend this treatment earlier in the pathway for ALL patients, before the patients have fully relapsed. This will allow patients to achieve undetectable MRD and give them an opportunity to have a stem cell transplant with the best chance of success. The ability to avoid relapse means patients avoid the emotional and physical effects that accompany being told their leukaemia is worsening again. The SMC has also given this opportunity to patients who have tried more than one alternative treatment; these patients are traditionally more difficult to treat and have fewer treatment options left.”