Myeloma is a particular focus for us – over 4,000 people are diagnosed with it each year in the UK, representing one in every 10 new cases of blood cancer.
Myeloma is currently considered incurable by standard treatment, which (when diagnosed, or if it returns) typically consists of chemotherapy and steroids to control it.
Younger, fitter patients may be able to withstand more intensive treatment, but the majority of patients are over 65 when diagnosed and receive less intensive therapy. Other treatments are used to relieve problems that myeloma can cause, such as bone pain, fractures and low numbers of red blood cells.
We’re getting better at treating the disease, and five-year survival rates have risen steadily over the decades – from around 12% in the early 70s, to 47% in the present day. But, sadly, it's still one of the blood cancers with the poorest long-term outlook and we desperately need more effective and kinder treatments.
That's why we're investing in myeloma research. We currently have 20 active or imminent myeloma research projects, totalling £6.65 million.
What is myeloma?
Myeloma affects a type of white blood cell in the bone marrow, called a plasma cell, which normally produces antibodies to fight infection. In myeloma, genetic errors in these cells lead to uncontrolled cell growth and division, and trigger them to churn out high volumes of a single, faulty antibody, called a paraprotein. This occurs in the bone marrow in many places in the body, so is sometimes called multiple myeloma.
The build-up of abnormal plasma cells and the action of paraprotein often leads to symptoms such as weak or painful bones, tiredness and shortness of breath, sickness, frequent infections, and eventually kidney failure.
To give a sense of how we’re tackling this area of patient need, here’s an overview of some of the things our researchers are working on.
Learning more about how myeloma works
Most of the genetic changes that contribute to the development of myeloma are acquired during our lifetime. Most often, these are due to chance errors creeping in when our cells make copies of themselves as part of normal day-to-day function.
But some genetic factors inherited from our parents, which may not trigger cancer themselves, can influence the activity of other genes and raise the risk of developing the disease. Research at The Institute of Cancer Research in Sutton is comparing DNA samples from myeloma patients with those from healthy people, with the aim of teasing out these inherited genetic features and providing clues as to how they contribute to cancer formation.
Work in Southampton is focusing on finding the variety of acquired genetic faults in a particularly hard-to-treat form of myeloma. The researchers are looking at how genetic alterations vary from person to person and, crucially, from cell to cell within a single patient, to see if these are linked to patient outlook. This will help unpick how and when these DNA errors occur in the progression of myeloma, which will be crucial in devising new ways of cutting off the disease at its root.
Trialling new treatment combinations
This trial is testing a new drug combination for myeloma patients with a specific type of genetic fault, who currently have a particularly poor prognosis. It’s the first of its kind to use genetic information in this way to match patients to suitable drugs that are targeted at the biological faults driving the disease.
These types of precision treatments are vital not only to more effectively kill all the cancer cells, but also to better protect healthy tissue and reduce the difficult side effects associated with traditional chemotherapy. This approach is not only the future of myeloma therapy but of cancer therapy in general.
Tackling bone damage caused by myeloma
Our work in Sheffield is taking a similar precision medicine approach to tackle the twin problems of devastating bone destruction and disease relapse. Firstly, they're developing combinations of drugs that can build new bone and prevent bone removal. And, secondly, they're seeking out the hidden, resting myeloma cells responsible for relapse and discovering ways to hit these with targeted treatments.
Researchers at Imperial College London are scanning DNA samples from patients for new genes whose activity levels are disrupted in myeloma, including those involved in destruction of bone. They are testing whether using drugs to block these cellular signals is a potential way of treating myeloma bone disease.
Once these studies have shown potential drugs look safe and effective in cancer cells and animals in the lab, the next step would be to start carefully controlled clinical trials to test the same in patients.
Looking for ways to prevent myeloma
Before a myeloma starts, patients develop a non-aggressive blood cell disorder called monoclonal gammopathy of undetermined significance (MGUS). Only one or two in a hundred people with MGUS will develop myeloma, and the reasons why only some patients do is not well understood. Our researchers in Oxford have identified that progression of MGUS to myeloma is associated with low levels of a hormone called adiponectin and they want to understand why this is.
The work in Southampton to detail genetic errors cell by cell is also applying this technique to MGUS. This will give an unprecedented picture of the key genetic events that drive progression to myeloma.
These findings could be important for the diagnosis and treatment of MGUS. Understanding the biological readouts linked to progression to myeloma could help doctors more accurately predict who is at highest risk and who would benefit from keener monitoring. And, if we know this, and by targeting the right cellular signals, doctors may be able to intervene with mild therapies to stop myeloma in the first place.
Thanks to all those who support us to do this kind of research – without you, it wouldn’t be possible.