CML is usually diagnosed in its slowly developing or ‘chronic’ stage and drugs called ‘TKIs’, taken daily in tablet form, normally can prevent the leukaemia from reaching its more aggressive ‘advanced’ phase, which is generally fatal. Since their introduction in the early 2000s, TKIs have effectively turned a once deadly cancer into a chronic disease with a normal life expectancy for most patients.
While TKIs are able to reduce the levels of leukaemia cells in the blood to extremely low levels in patients – and in some patients their leukaemia is undetectable – they are not able to eradicate all leukaemia ‘stem cells’ that drive the disease. It was assumed that patients would need to remain on TKIs for life to prevent the CML from returning.
A clinical trial, called DESTINY, run by the University of Liverpool across 20 hospitals in the UK, has found that many patients who have consistently responded well to years of treatment can reduce their dose and then stop altogether. Before starting the trial, which had funding from Bloodwise, all patients had been taking one of three common TKI drugs - either imatinib, nilotinib or dasatinib - for an average of seven years.
The trial results are likely to influence future medical guidelines on how the long-term treatment of people with CML is managed.
Common side effects of TKIs include chronic headaches, stomach problems and fatigue, and women are typically advised not to conceive children while taking the drugs due to the high risk of birth defects. It is estimated that there are over 5,000 people with CML in the UK currently on TKI treatment, which costs the NHS on average around £23,000 per year for each patient.
The trial, led by Professor Richard Clark at the University of Liverpool’s Institute of Translational Medicine, halved patients’ standard TKI daily dose in the first year and then stopped treatment altogether. As well as patients with almost undetectable leukaemia, the trial also included some patients whose leukaemia was stable though rather more active - a group of patients who had never been studied before by other clinical trials investigating whether people with CML can stop treatment.
Patients were carefully monitored with specialist blood tests every one to two months. If signs of the leukaemia returning were detected, patients were immediately put back to the full dose of their TKI treatment.
Three years into the clinical trial, the latest results were recently revealed at the prestigious Annual Congress of the European Haematology Association. They showed that 72% of patients who had very low or undetectable leukaemia at the start of the trial remained in remission two years after completely stopping daily treatment.
These results are better than any other worldwide clinical trial, which the researchers believe is due to a more gradual withdrawal of TKI treatment. And 36% of patients who had rather higher levels of leukaemia at the start of the trial remained in remission two years after stopping treatment.
Crucially, all the patients whose leukaemia came back after stopping TKIs were rapidly returned to deep remissions when they resumed treatment. This confirms that, if carefully supervised, attempting to stop treatment carries little long term risk to the patient.
Professor Richard Clark, who is leading the trial, said: “We’ve found that reducing and then stopping treatment is safe for most patients with CML who have had stable and excellent responses to TKI therapy after some years of treatment, and is associated with reduced symptoms.
“Overall our findings are better than any other studies world-wide, and imply that our unique gradual withdrawal of treatment might be important. We don’t yet fully understand why our results are so good, but this is a happy problem to have!”
Dr Alasdair Rankin, Director of Research and Patient Experience at the blood cancer research charity Bloodwise, said: “Since their introduction, TKI drugs have transformed the lives of people with CML, enabling many to live a relatively normal life simply by taking tablets every day. But treatment is life-long, and some people will experience serious side effects that severely impact their quality of life.
“The results of this study are really encouraging, and suggest that under careful monitoring, many people who are doing well on their TKI may ultimately be able to reduce or even stop taking their medication. But reducing or stopping treatment will not be right for everyone, so it’s really important that patients with CML talk to their doctor before considering any change to their medication.”
One of the first ever targeted cancer treatments, the TKI drug imatinib, also known by its brand name ‘Gleevec’, made the cover of TIME magazine in 2001 - billed as the ‘new ammunition in the war against cancer’.
Jeff Tate, from Preston, was diagnosed with chronic myeloid leukaemia in 2003 at the age of 42. After running the London Marathon for charity, he gave a blood sample, which picked up that he had leukaemia. He was prescribed Gleevec, which he took every day for over 10 years until joining the DESTINY trial in Liverpool.
He said: “I responded very well to Gleevec. I took it every day with my breakfast and it became part of my daily routine. The side effects were hot sweats at night and people said my short-term memory wasn’t as a sharp as it had been, but I know I was one of the lucky ones”.
“When I was offered the opportunity to be involved in a trial to reduce and eventually stop taking Gleevec I couldn’t say no. The hot sweats have stopped, although I still get anxious before a blood test, worrying about whether the leukaemia has returned. But I’ve always had a positive outlook - I know that if future results are positive (for leukaemia), I will be prescribed further medication and the leukaemia levels will be controlled.”
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