Thousands of Britons battling incurable blood cancer could be thrown a lifeline thanks to a new ‘two-pronged-attack’ combination drug therapy.
Until now, patients with chronic lymphocytic leukaemia – also known as CLL, one of the most common types of blood cancer in adults – had to endure repeated rounds of gruelling chemotherapy to keep their symptoms at bay.
More than 4,600 people are diagnosed with CLL in the UK every year. For most, the treatment eventually stops working and almost 1,000 die from the disease annually.
Now, following promising early results of a trial testing a new drug combination, experts believe they may potentially have a cure.
The trial, called Clarity, recruited 54 patients in Britain aged between 20 and 80.
All had previously had chemotherapy and had been in remission before their cancer returned.
At the end of 2016, Lelia Duley was offered the chance to join the Clarity trial, and in February 2017 she began treatment
The group were initially given a dose of the targeted drug ibrutinib every day for two months. A daily dose of venetoclax, a type of chemotherapy, was then added.
And the results have been astounding. After two years, 20 patients showed no signs of cancer in their bodies and were able to stop treatment entirely.
‘The response rates we have seen have far exceeded what we had expected,’ says lead investigator Professor Peter Hillmen, from Leeds Teaching Hospitals NHS Trust.
‘The fact that some patients have already been able to come off treatment and remain leukaemia-free is very encouraging, and we hope more will soon be able to do the same.
‘We can’t find chronic lymphocytic leukaemia in their blood or bone marrow.’
Dr Alasdair Rankin, director of research at the blood cancer charity Bloodwise, which is funding the trial, said: ‘This type of blood cancer remains incurable today, but it’s a really exciting time. It’s not a matter of if but when we have a cure for chronic lymphocytic leukaemia, and Clarity is a step in the right direction.’
Chronic lymphocytic leukaemia, which affects around a third of people diagnosed with leukaemia, has long been considered incurable. It is a disease of the immune system – the body’s defence against disease and infection – and is rare in people under the age of 40.
It occurs when the bone marrow, the spongy material inside bones responsible for manufacturing blood cells, makes too many lymphocytes – a type of white blood cell – that don’t work properly.
Instead of protecting the body, the malfunctioning immune cells multiply in an uncontrolled way and ‘crowd out’ functioning ones, increasing the risk of infection.
The cancer is often picked up during routine health checks and blood tests, before any symptoms develop. But it may result in severe fatigue, night sweats, unusual bleeding and bruising.
The disease can also cause glands in the body to swell and develop into lumps.
This is the result of a build-up of abnormal lymphocytes in lymph nodes, usually in the neck, armpits and groin.
It may also cause swelling in the spleen – the most important organ in the immune system – stopping it from working properly.
The cancer is often picked up during routine health checks and blood tests, before any symptoms develop (stock image)
Initially, most patients will simply be monitored, as the cancer can be very slow to progress. But about half will go on to need some form of intensive chemotherapy, which works by destroying abnormal cells and interfering with the way they multiply.
This usually makes symptoms go away for between two and six years. But in most cases, the gap between treatment will get shorter and shorter until chemotherapy is no longer effective.
Some patients may be offered targeted drugs, which help the body control growth of the cancer, or radiotherapy, to shrink enlarged lymph glands or a swollen spleen.
Stem cell or bone marrow transplants are very rarely used to try to control or get rid of CLL completely. Until now, this has been the only potential cure for patients. But the treatment is intensive, risky for older people and can result in serious complications.
Patients must first have high-dose radiotherapy or chemotherapy to destroy cancerous cells in the body, before being given donated stem cells, usually from a brother or sister, through their veins.
In some patients, the transplanted cells may attack other cells in the body, which can be life-threatening. But the new combination treatment could offer a better alternative.
In disease-free adults, white blood cells multiply very quickly to fight infection before self-destructing. But researchers have found that in patients with chronic lymphocytic leukaemia, the switch that triggers growth is permanently switched on.
The abnormal white blood cells also fail to self-destruct in the same way as healthy cells.
In the Clarity trial, the researchers use ibrutinib to target and switch off a protein linked to cell growth and movement in the cancerous blood cells. At the same time, venetoclax is used to switch off the proteins in cancer cells that help to keep them alive.
Professor Lelia Duley, 61, from Southwell in Nottinghamshire, is one of the patients involved in the trial. The mother-of-two was diagnosed with chronic lymphocytic leukaemia in 2009 after a large kidney-bean-shaped lump emerged on her shoulder blade. ‘I’d been feeling more tired than usual and I suspected the lump was something cancerous, but when I got the diagnosis, I was stunned,’ Lelia says.
Initially, she was put on the watch and wait programme, but within a year her cancer had progressed.
Experts hope the new combination treatment could be made available as early as 2023 (stock image)
‘My trousers were too tight because my spleen was so enlarged,’ she recalls. ‘I wasn’t surprised to be told it was time to have treatment.’
Lelia, who was previously director of the Nottingham Clinical Trials Unit at the University of Nottingham, and led pioneering research into treatment for premature babies, was given a form of chemotherapy from September 2010 to early 2011.
‘I responded well and was put into remission, but I knew I wasn’t cured,’ she said.
Four years later, she began to relapse, suffering from a series of infections, including the painful skin condition shingles.
At the end of 2016, Lelia was offered the chance to join the Clarity trial, and in February 2017 she began treatment. ‘Trying a new treatment is a gamble but it offered some hope,’ she says.
‘I’d been given ten years when I was first diagnosed at 51. I wanted the chance to share my children’s lives a bit longer.’
The venetoclax initially caused fatigue and a loss of concentration.
But Lelia’s condition went on to vastly improve. She was even well enough to walk the West Highland Way – a 95-mile multi-day hike – in Scotland last year.
She said: ‘If I get through two tests with no signs of the leukaemia left, I can stop treatment altogether. At the moment there are still tiny numbers of cancer cells left, but I’m technically in remission.’
Four patients involved in the trial reacted badly to ibrutinib and pulled out of the trial, while one patient developed a more aggressive form of blood cancer and died.
But overall results were so promising that the study was extended to a third year, so patients could continue to benefit from the combined dose. Because of the success of the trial, the drug combination is now also being tested in a separate University of Leeds study involving 1,600 patients.
Both drugs were approved for individual use on the NHS by health watchdog the National Institute for Health and Care Excellence two years ago.
However, they aren’t yet available together outside of clinical trials.
Experts hope the new combination treatment could be made available as early as 2023.
‘The combination would have to be licensed by the European Medicines Agency and then it would have to go through the National Institute for Health and Care Excellence and either be fully approved or put on the Cancer Drugs Fund,’ Prof Hillmen says. ‘But if we have positive results in 2022, it’s feasible the treatment would be available the following year.’
For more information, visit bloodwise.org.uk.