Professor Chris Pepper from the Institute of Cancer & Genetics at Cardiff University is one of the world’s top experts on chronic lymphocytic leukaemia (CLL).
Just over 20 years ago, Chris was a breast cancer researcher, but he changed course when his dad was diagnosed with a disease called CLL. “I knew nothing about it so I toddled off to the library and tried to find out what I could. I was shocked about how little was known about the disease: it was probably a combination of naivety and arrogance that made me think I could do better and make some inroads.”
CLL affects lymphocytes, a type of white blood cell. It’s a chronic leukaemia, which means it usually (but not always) develops more slowly – people usually live with it over a longer period. It’s the most commonly diagnosed leukaemia in the UK, with 4,100 people diagnosed every year, and it’s most common in older patients, with the average age of diagnosis around 70.
People’s quality of life suffers with CLL in particular, because large numbers of patients are on what’s called ‘watch and wait’. This is where they don’t need treatment immediately but are instead monitored by their healthcare team, who look for signs that their CLL is getting worse and may need treating. Many people call this ‘watch and worry’.
CLL is often described as an incurable disease, and because of the slow rate of disease progression and the fact that five-year survival rates are relatively high (around 87%), CLL was described by some as a forgotten, ‘Cinderella’ cancer, with little research into improving treatments.
But experienced researchers like Chris are now seeing a rapid change as the biology (how the disease develops and operates in our body) has become better understood. We’ve witnessed the translation of this understanding into patient benefit on a dramatic scale.
“There’s been remarkable headway in the last five years in terms of understanding how this disease works,” says Chris. “The world has changed for CLL patients, beyond recognition, and I confidently predict that within 10 years this disease will become much less of a clinical problem.”
So how will we beat it?
Research funded by Bloodwise has laid the foundations for some very promising new drugs that target the faulty signals at the root of the cancer, rather than more toxic chemotherapies that affect healthy, as well as cancerous cells. We’ve learnt from success in treating another leukaemia, chronic myeloid leukaemia (CML), where many patients can now take a ‘magic bullet’ pill each day and – for the most part – get on with their lives. These precision drugs are called tyrosine kinase inhibitors (TKI), and they work by counteracting the effect of the protein that causes the leukaemia.
Similarly, we aim to turn CLL into a condition that people keep at bay with just a daily pill. But CLL is a different type of disease to CML: the biological triggers that cause it in each person are more varied. So it’s likely that successful treatment will require lots of different ‘magic bullet’ pills, used in combinations that are tailored to each patient’s disease.
We need to find out which of these new drugs are best and how to combine them, to bring the best outcome for each individual patient.
It’s about determining doses, how often to take the drugs and what to take alongside them. The UK is ideally placed to lead these investigations, given that we have multiple internationally recognised research groups working on different aspects of the disease in close collaboration – from the laboratory to the clinic.
But we need to develop better infrastructure: a national-level clinical trials portfolio for CLL. We’re already having some success in boosting the recruitment of patients through the existing Bloodwise Trials Acceleration Programme (TAP), but we need to apply this model on a bigger scale to beat CLL.
Professor Peter Hillmen, at Leeds’ St James’s University Hospital, ran a clinical trial called IciCLLe, which became the first trial in the TAP network to complete patient recruitment. It looked at ways to enhance the effectiveness of a TKI called ibrutinib, which has been shown to extend survival in patients who stop responding to traditional chemotherapy, with limited side effects. IciCLLe took place at eight hospitals across the UK and reached its target of 40 patients in just under 10 months thanks to our TAP model.
Professor Hillmen said: “I’ve already run one successful clinical trial through TAP and I’m setting up two more. These trials are vital in finding out how these new drugs can be safely combined to bring the best outcome for each individual patient.”
One such patient is Sarah Weltman, who started on the trial in 2014 and is now in remission: “my response to the treatment was amazing and I’ve really not suffered any significant side effects. One of the huge benefits of ibrutinib is that I was able to continue to work and stay active, two things I was petrified of losing.”
The treatment has been so effective that Sarah is now able to cycle hundreds of miles at a time, raising money for Bloodwise to fund more of the research that saved her life.
Unfortunately though, we already know these new drugs won’t save every patient, so we need to understand why some patients don’t respond and how drug resistance develops.
As a first step, we need to bank tissue from patients taking part in these new trials. Bloodwise invest in cell banks and databases across the UK. Professor Andy Pettitt set up the UK CLL Trials Biobank at the University of Liverpool, which is supported by Bloodwise and Cancer Research UK. It’s a vital resource that enables scientists to study the biology of blood cancer in more detail.
Better understanding of the biology of the disease also leads to better prognostic tools. We know that every person’s disease is different. For some patients, their cancer doesn’t develop much after diagnosis and they might not need treatment straight away, but in others the disease is aggressive and treatment is needed quickly.
Professor Duncan Baird, one of our researchers at Cardiff University, has developed a genetic test that looks promising in being be able to predict, at diagnosis, whether people will need treatment or not. His test, which analyses the genetic architecture within CLL cells, has brought very positive results so far, but what he and his team need to do now is test it in real life – in a clinical trial, on larger numbers of patients.
We want to get to a place where we can tell patients, at the time they’re diagnosed, if their CLL will ever need treating. We know with the right funding and strategic approach, we can turn ‘watch and wait’ into ‘watch and live’. While it’ll be hard for patients to know they have a cancer that will probably need treatment in the future, we’ll have a suite of effective, targeted drugs for when they do. Many patients have told us that this certainty will help them get on and live their lives until that time comes. And for some patients, they’ll know that their CLL will never develop to an extent that they need to worry about it. Through the three pronged approach – trialling combinations of emerging drugs, improving tests so we can determine if and when patients need treatment, and developing new, targeted drugs so we can save the life of every patient – we believe can effectively beat CLL within 10 years.
As of October 2015 Bloodwise currently has £9.8 million invested in 31 active grants for CLL research. 25 awards have been given since 2013, with three recently granted in November. The future is looking promising, and Professor Chris Pepper states confidently that if we do the right things and get the financial support we need, he may be back working in the breast cancer field soon enough.
“The world of CLL is changing remarkably and improvements in therapy may well put me out of a job: that’ll be a great thing.”
£25 a month over a year could pay for high quality vials to store samples in our biobank for 50 patients. You could help us understand why some people don’t respond to treatment, so we can save the life of every CLL patient.