It’s an exciting time in blood cancer research. As we deepen our understanding of the biology of blood cancer, researchers are developing better treatments than ever before, and we’re even beginning to talk about cures for some types of blood cancer where it would have been unthinkable a decade ago. Let’s take a look at the brilliant progress that’s been made in the past few years…

CAR-T: a cure for blood cancers?

CAR-T is a new treatment that can put blood cancer into remission or cure it – even in people who would otherwise have only a few months to live. Not only that, CAR-T cells should be able to prevent relapses, since they are designed to remain active in the body for a long time. This completely new approach to tackling blood cancer works by taking T cells from patients, adding a chimeric antigen receptor (CAR) that can bind to cancer cells, then returning these CAR-T cells to the patient via an infusion. Back in the bloodstream, the CAR-T cells can hunt down and kill cancer cells with much greater efficiency than the patient’s unmodified T cells.

Last year, CAR-T therapy was made available on the NHS to children and young adults with B-cell acute lymphoblastic leukaemia as well as adults with diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma – though only those who have exhausted all other treatment options. The first patient in the UK was treated just before the end of the 2018.

CAR-T isn’t without its problems: the major hazard to patients is from cytokine release syndrome in the days immediately following a CAR-T cell infusion, and since it’s a relatively new treatment we don’t know what the longer-term side effects of the procedure are. However, the danger of cytokine release syndrome can be mitigated by keeping patients under observation following the infusion procedure, and follow-ups from clinical trials are keeping an eye on the long-term progress of people who’ve had the treatment.

A second set of problems relate to the cost and limitations of the CAR-T treatment itself. The only versions available currently require the modification process to be carried out anew with T cells from each individual. On top of that, CAR-T is only available to people who have cancers affecting B cells, since we can’t yet arm T cells to attack other T cells. There are researchers working on each of these problems, developing CAR-T treatments for other types of cancer, and Bloodwise is funding research on a ‘universal’ CAR-T therapy that doesn’t need to be made afresh for each individual. This universal therapy is also designed to treat T cell acute lymphoblastic leukaemia.

Acute myeloid leukaemia: targeted treatments

It’s not just CAR-T where breakthroughs are being made.

For a long time, finding ways to effectively treat acute myeloid leukaemia (AML) have been among the most intractable problems in blood cancer research. AML’s symptoms (fever, fatigue, shortness of breath, for example) can easily be confused with ‘feeling generally unwell’, which can delay diagnosis of this rapidly-developing cancer. This means that at the point when a clinician confirms that a patient has AML, treatment is often urgently needed. Unfortunately, there are several different genetic mutations which can cause the disease, and it can take a few days to find out which of these is in play in order to provide the correct targeted treatment. If the patient can’t afford to wait, or a targeted treatment doesn’t exist for the type of AML they have, then the only other option is intense and toxic chemotherapy, which not everyone is healthy enough to tolerate.

Chemotherapy has been the mainstay of AML treatment for decades, but in 2018 we saw several new targeted treatments become available. This is great news, but the drugs are limited to a small population of AML patients, and an increase in the number of targeted treatments means that matching up the right treatment to the patient is now more important than ever before.

This is where the BEAT AML Master Clinical Trial comes in. The trial is for people over 60 with newly diagnosed AML, and its aim is to match a targeted drug to each person’s AML within 7 days. Of the 350 people who’ve taken part in this trial, 95% have been assigned a new targeted therapy. Having a test that can quickly match kinder treatments to each individual person will have a major impact on survival time, especially for those who are unable to tolerate intense chemotherapy.

We’re also expanding the number of targeted treatments available through a study we have funded on the genetics behind different types of AML. This research has revealed the critical founder mutations that act as trigger points for the development of different types of AML. Because cells with the same founder mutations always follow the same development pathway, the researchers were able to identify key places to target individual types of AML. We could soon be looking at individualised treatment for all forms of AML, not just a few.

Chronic leukaemias: on the cusp of a cure

Unlike acute blood cancers, chronic blood cancers are generally slow-growing, but need to be monitored and kept in check to prevent or slow further development.

Before 1998, the only way to treat chronic myeloid leukaemia (CML) that had reached an advanced stage was with a stem cell transplant. The advent of tyrosine kinase inhibitors (TKIs), which can be taken as a daily pill, changed CML from a potentially fatal condition to one with a normal life expectancy for most patients. Unfortunately, TKIs can cause many unpleasant side effects like fatigue, diarrhoea and headaches, and until recently it was thought that everyone taking TKIs would need to do so for life.

In the last two years, the Bloodwise-funded DESTINY trial has made it clear that at least some people whose CML is stable or at undetectable levels in tests can slowly reduce and eventually stop taking TKIs without long-term risk of relapse. For those whose CML does relapse, resuming TKIs can swiftly return them to a state of deep remission. This exciting finding is unlikely to apply to everyone, but it will help change the way doctors treat people with CML who are doing well on their TKIs, giving them the wonderful prospect of being free from their medication and its side effects.

Things are looking even more promising for people with chronic lymphocytic leukaemia (CLL), which has historically been treated with chemotherapy and/or immunotherapy. However, a new generation of targeted drugs is changing the way we treat CLL. A combination of two of these targeted drugs – ibrutinib and venetoclax – is showing great promise in the Bloodwise-funded CLARITY trial, for people with CLL that has not responded to other treatments. Remarkably, every single one of the 50 people who’ve taken part in this trial has responded to treatment, with some doing so well that they have been able to finish treatment and remain in remission. We might, at last, be looking at a cure for this cancer.

The future

Although we have seen some amazing breakthroughs in blood cancer recently, death rates for some blood cancers remain very high, and there is still much to do. One in 19 of us will have a blood cancer at some point in our lives, and blood cancer is the third biggest cancer killer in the UK, claiming over 15,000 lives every year – more than breast cancer or prostate cancer. To keep up the momentum of the improvements we have seen in the last few years, and for those improvements to apply to more blood cancers, we need to make sure that investment in blood cancer research continues.