Surviving cancer against the odds can give patients a new lease of life. But what if the very drugs that save them then leave them with another painful, incurable disease?
That’s a reality cancer specialists and patients around the world are facing, as more and more people benefit from immunotherapy — groundbreaking new drugs that harness the body’s immune system to attack cancers.
In many cases, these diseases are otherwise untreatable.
The first immunotherapy drugs for cancer — usually given as weekly or fortnightly infusions — were licensed in the UK in 2011 for advanced melanoma, the most severe form of skin cancer that has spread to other organs. And they have been hailed as game-changers against these tumours.
The treatment costs around £100,000 per patient per year, and has potentially crippling side-effects. A doctor and patient (file photo)
In the 1990s, for example, patients with advanced melanoma survived an average of just six months. Today, the average survival rate is three to five years, and longer in some cases, thanks to immunotherapy drugs such as ipilimumab (brand name Yervoy), pembrolizumab (Keytruda) and nivolumab (Opdivo). These all work by bolstering the body’s defences to destroy cancer cells.
Patients with otherwise untreatable tumours on the lungs, kidneys, head and bladder are also now benefiting from immunotherapy, which costs around £100,000 per patient per year.
But as prescribing of the drugs widens, studies are suggesting that thousands of patients are paying a price for the treatment’s success. Research shows that around one in ten patients given immunotherapy for cancer will develop potentially crippling rheumatoid arthritis as a side-effect.
Rheumatoid arthritis, an auto-immune condition in which the immune system wrongly attacks the cells that line the joints, affects around 350,000 people in the UK, causing painful, inflamed joints and extreme fatigue.
One in ten patients given immunotherapy for cancer develop rheumatoid arthritis
The first report of such side-effects was in 2018, when doctors at the Johns Hopkins Arthritis Center in Baltimore, in the U.S., investigated 30 patients who developed joint problems after taking the immunotherapy drugs ipilimumab, pembrolizumab and nivolumab. All of them had developed pain and inflammation in both knees within weeks of starting immunotherapy. Those on two immunotherapy drugs at the same time — a common practice to boost their effectiveness — also had inflamed lungs and bowels, reported the journal Seminars in Arthritis and Rheumatism.
Most improved after being given large doses of steroids to dampen down inflammation, but a third needed stronger medicines called TNF inhibitors (which block a protein called tumour necrosis factor-alpha, which promotes inflammation).
Although very effective, these drugs can also have side-effects, ranging from chronic fever and bruising to numbness and blurred vision. And while they can ease symptoms, they are not a cure for rheumatoid arthritis.
So how can drugs designed to quash cancer end up triggering problems with our joints?
Rheumatoid arthritis is triggered when the immune system goes haywire and starts destroying healthy joints. Scientists think the cancer drugs may be tipping the immune system into self-destruct mode in some patients.
These drugs work by turning off specific proteins found on the surface of immune system cells, which are there to stop it attacking the body’s healthy tissues.
Cancer cells use this built-in protection system to slip past the body’s defences. But once these proteins have been deactivated by the immunotherapy drugs, the immune system is free to detect tumour cells and destroy them.
However, in some cases, it seems this leads to the destruction of healthy cells, too, such as those in the bones and joints.
And it’s not only rheumatoid arthritis that’s the problem. Other research shows that around 1 per cent of patients on the drugs develop type 1 diabetes — another common auto-immune disorder, which occurs when immune cells attack the pancreas, leaving sufferers dependent on daily insulin injections to control blood sugar.
Such is the scale of the problem that earlier this year, the European League Against Rheumatism — a body representing rheumatoid arthritis patient and doctor groups across Europe — set up a taskforce to investigate.
It developed guidelines to help arthritis and cancer specialists to be on the lookout for joint problems caused by the new generation of cancer drugs, in the hope that patients can be treated earlier and will be therefore less likely to suffer severe illness.
In acute cases, treatment might have to be withdrawn and replaced with something else, such as chemotherapy.
Alan Melcher, a professor of translational immunology at the Institute of Cancer Research in London, says as more people are treated with immunotherapy drugs, doctors are getting a clearer picture of the long-term side-effects.
Yet for many patients it’s still well worth the risk, he adds: ‘These are still fairly new drugs. But there’s no doubt in my mind that the pros outweigh the cons.’