The Road to Beating Chronic Lymphocytic Leukaemia
From defining two types of CLL, to thinking about how we might prevent CLL altogether, this blog is based on a conversation with Professor Freda Stevenson about how we improve things for people with the disease.
Professor Freda Stevenson
Professor Freda Stevenson is a Professor of Immunology at the University of Southampton. Her achievements in the field of chronic lymphocytic leukaemia (CLL) include the discovery that CLL, previously thought of as one type, can be divided into two types, that progress very differently. The difference lies in the make-up of the CLL cell, and whether a specific form of a protein exists on the surface. This protein can tell us how the tumour is likely to progress and provides a target for drug therapy. This has changed how clinicians treat the disease worldwide. Freda spoke to Blood Cancer UK about how far we’ve come throughout her career, and what we need to do to continue making progress for people with CLL. This blog, in our words, summarises her thoughts.
Treatment has changed dramatically over the years
When Freda first started investigating CLL, patients would ask their clinicians what would happen to them after diagnosis and clinicians were unable to answer, so they simply said they’d just keep an eye on them. They knew that some people with CLL would do really well, and some would do badly, but had no way of differentiating between the two groups.
Discovering two distinct disease types
So, in 1999, Freda and others set out to understand why this difference in behaviour of the disease existed. What they found was staggering and would change how CLL was viewed around the world. While all CLL cells looked similar down a microscope, a more in-depth analysis, carried out by Freda and a team of researchers, showed that there were two very different types of disease, each of which had a different protein that could indicate how the disease was likely to progress. The protein can now be studied, and when combining this test with an assessment of the patient, it allows clinicians and patients to know how their cancer is likely to behave.
Attacking cancerous cells from all angles
Those who have CLL with the poorer prognosis are more likely to need treatment, but Freda explained that instead of the chemotherapy given in the past, which actually was ineffective, alternative treatments are now available that specifically target the distinctive protein that exists on the surface of a CLL cell. These drugs have made a huge difference to people with CLL and are able to put patients into remission from their disease. Treatment comes as a pill, which means people don’t need to be in hospital and side effects tend to be mild. But like all treatments, over time the cancer can stop responding and people can see their disease return. When you just target one feature of a cancer cell, the cells that make up the tumour will do all they can to stop being destroyed by treatment and can switch on other processes that allow it to survive, causing the cancer to come back. Freda explained that to try to stop this happening, researchers are now trying to attack the cancerous cells in more than one way, to give the cancer less chance of escaping treatment. This is now being trialled using combination treatments like venetoclax and ibrutinib and there are high hopes for this treatment combination.
CLL is most common in older people and these new targeted treatments are less toxic than the old chemotherapy. People often achieve remission after treatment but they will be monitored in case their cancer returns
A treatment free future?
Freda isn’t certain of whether we’ll get to a stage where people can come off treatment completely and explains that clinical trials will need to be done to see if this is a possibility. She thinks that clinicians will always monitor people with CLL in case their disease returns. There is also a continuing need for the research community to understand more about how CLL cells behave. The goal is to find a “cure” for CLL which has certainly become a possibility.
Shifting the focus
Freda believes that improving the outcome for CLL isn’t necessarily about removing every single tumour cell. CLL is a very different disease from the acute leukaemias, where cancer cells rapidly divide and grow. The average age at diagnosis of CLL is 70 and so if there are ways to control the cancerous cells, people can probably live for 20 years without the need of intensive therapy, hopefully giving them a normal life expectancy.
Of course, for younger people who are diagnosed this is more of a problem because their disease needs to be controlled for more than 20 years to give them a normal life expectancy, and this will need a careful treatment approach together with emerging new drugs based on good science.
Scientists now understand what process drives the growth of CLL cells, and drugs such as ibrutinib target this process, but there are new drugs that target different parts of this process in the pipeline. So, if someone’s cancer stops responding to ibrutinib, there would be other options available to them and this is the key to improving things for younger people with the disease.
Stopping CLL in its tracks
At the moment, CLL is diagnosed when people have a certain level of tumour cells in the blood but there are people with less than this “cut off”. This is called monoclonal B-cell lymphocytosis (MBL). and people who have this might develop CLL at a later stage. Freda explained that if the link between MBL and clinical CLL could be understood, there might be an opportunity to intervene and prevent CLL from occurring. This would mean clinicians could intervene before the disease weakens the immune system, as it’s the weaking of the immune system that is dangerous for people who are then more susceptible to infection and becoming seriously ill from this.
It's not all about clinical trials
Freda believes that to keep making progress, we need to do more than just test different combinations of drugs in clinical trials. Work in the lab is still integral to making progress as it’s still not entirely understood how CLL cells survive, how the immune system becomes so weak, or what happens after drugs are given to people and how resistance develops. These are problems that only laboratory work will solve.
Ultimately, Freda believes that we’ve got to a good place in CLL but it’s not perfect, and there’s more to learn. She thinks that if we can answer some of the outstanding questions we could get to a stage where we can predict if and how CLL develops and aim for prevention or cure. At the very least, Freda thinks we’ll be able to control the disease so that it is not life-limiting.
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