The National Institute of Health and Care Excellence (NICE) recommends the use of blinatumomab

The National Institute of Health and Care Excellence (NICE) have today recommended the use of blinatumomab for Philadelphia chromosome negative (Ph-ve), CD19 positive, B cell precursor acute lymphoblastic leukaemia (ALL), who have MRD of at least 0.1%.

The brand name for this treatment is Blincyto and it is manufactured by Amgen.

Blinatumomab has previously been approved, in 2017, for use in ALL patients who have relapsed and is often used to control the disease before the patient has a stem cell transplant. However, this was a proposal to use the drug in a different population of patients (see “why has NICE approved it twice?” below)

What is blinatumomab?

Blinatumomab is a type of drug called immunotherapy, which means it is designed to help the patient’s immune system to 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 they might if they had to just meet 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 has NICE approved it twice?

A drug is approved by 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. NICE examines 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 NICE to decide if blinatumomab will also work for the indication of patients that haven’t relapsed, yet 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, whereas being MRD negative or undetectable is when cells with these markers can’t be found.

The problem with MRD testing is that it is new and not everyone uses the same techniques to check a patients 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.

What is the significance of MRD for this decision?

It has been shown that the fewer leukaemia cells patients have in your 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, attended the NICE committee meetings to explain the importance of MRD as a prognostic factor (i.e. the number of cells in a patient’s body indicates their likelihood of relapse) and hence argue for this population of patients to have access.

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”.

“A diagnosis of acute lymphoblastic leukaemia can have a huge emotional impact on the lives of patients, as well as their family and friends,” said Zack Pemberton-Whiteley, Patient Advocacy Director at Leukaemia Care. “We welcome the decision to recommend this treatment earlier in the pathway for ALL patients. 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. We are pleased that the NHS has chosen to pay for the drug earlier on, to spare patients and their families the extra harm of waiting for relapse before receiving the best treatment currently available to them.”