Scientists may have taken a big stride towards finding a cure for a type of blood cancer that has until now remained largely incurable.
Multiple myeloma has long proven to difficult to treat, although therapy can give patients years of extra life.
New approaches that help the immune system disease destroy the cancer cells may represent a step change compared to standard treatments, which have improved in recent decades.
A key new method involves adding a component called a receptor to T-cells – a type of white blood cell in the immune system – allowing them to better recognise and destroy the cancer.
Known as Car-T therapy – or chimeric antigen receptor T-cell therapy - it has achieved remission rates in continuing Israeli trials of about 90 per cent in patients for whom other treatments are no longer effective.
Follow-ups with the patients in Israel have taken place over six months, so longer-term outcomes cannot yet be assessed but scientists say results so far appear promising.
Educating T-cells
A form of immunotherapy, Car-T therapy has been used to treat other cancers and approval has in recent years been limited to treatment for multiple myeloma.
Prof Cyrille Cohen, head of the Laboratory of Tumour Immunology and Immunotherapy at Bar-Ilan University in Ramat Gan, said the approach involved "educating" the T-cells to recognise and kill cancer cells.
The therapy is based on targeting BCMA, a protein overproduced in multiple myeloma cells.
Imperial College London
Prof Cohen's laboratory designed and tested numerous prototype receptors to determine which were most effective at helping the immune cells to use BCMA to identify and destroy the multiple myeloma cells.
"It’s like playing with Lego. You need to find the right combination, the right distance between the two molecules, the right combination of molecules inside the T-cell that will activate the T-cell," said Prof Cohen, president of the Israel Society for Cancer Research.
His group narrowed the choice down to four receptors and used tests to find the most effective.
Clinical trials, led by Prof Polina Stepansky, have been taking place at Hadassah University Medical Centre in Jerusalem in conjunction with a US biotechnology firm Nexcella.
"So far they treated more than 70 patients, which is commendable if you take into account this was developed just by a university and hospital, not by a multibillion [dollar] company," Prof Cohen said.
The treatment works by taking blood samples from multiple myeloma patients and separating out and multiplying the T-cells, which are altered by having genetic material added to them so that they produce the receptor for the target protein. The cells are then reinstated to the patient.
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Multiple myeloma accounts for about 10 per cent of all blood cancers and about 1 per cent of all forms of cancer. It is more common in older people, especially those over 70.
The condition forms in the bone marrow and takes its name from the fact that typically it affects bones in more than one part of the body, including the pelvis, spine and skull.
Symptoms include brittle bones, persistent pain, tiredness and weight loss.
Other than in very rare cases it cannot be cured, although treatments, which may involve chemotherapy, steroids and stem cell transplants, can control symptoms and extend a patient's lifespan.
Researchers across the globe are looking to develop or improve Car-T therapies for multiple myeloma, including Prof Anastasios Karadimitris, director of the Hugh and Josseline Langmuir Centre for Myeloma Research at Imperial College London.
"They have certainly increased the time during which the patient will have no active disease or no clinically active disease and now there is emerging evidence that they will improve survival of the patients," he said.
"They have been really a very significant increment in our ability to treat this otherwise incurable blood cancer."
In one recently reported clinical trial, patients who had relapsed after having other therapy had three times as long without active disease when given Car-T therapy compared to standard multiple myeloma treatments.
"That’s really very, very impressive. Nothing so far in the recent history of multiple myeloma has achieved such results," Prof Karadimitris said.
High cost
A stumbling block to the wider use of Car-T therapy is price: treatment developed by commercial pharmaceutical companies can cost as much as $400,000 per patient.
However, when academic groups such as those in London or Israel, create the treatments, costs are likely to be much lower, possibly as little as one fifth of what they would be if they had been developed in the private sector.
It is "too early to say", Prof Karadimitris said, whether any of the Car-T therapies will create a complete cure, but he added they could lead to improved longer-term outcomes.
"Maybe we will see the best survival rates that we’ve seen historically. Whether it will be curative it’s difficult to say," he said.
Another emerging form of immunotherapy to tackle multiple myeloma involves specific antibodies, whereby one arm of the antibody engages with a T-cell while the other attaches to a cancer cell.
"There’s one such product licensed," Prof Karadimitris said. "It’s hard to tell if it’s as good as Car-T cells because there haven’t been comparisons but certainly the results look very, very good."
As other new treatments have been introduced in recent decades, prospects for multiple myeloma patients have already improved, with Prof Karadimitris describing survival rates as having doubled over the past decade to 15 years.
Treatments either now being trialled or soon to be introduced may be just the beginning, with more potent options likely to become available.
"There is a lot of belief that these very interesting and unprecedented results that we’ve seen already, although they don’t show a curative trend yet … we can improve further," Prof Karadimitris said.
He said the hope is that combining treatments could achieve what doctors call an operational cure, the disappearance of all signs of cancer for a prolonged period, which would represent a major step forward in the treatment of multiple myeloma.
