You do three different jobs. Could you talk us through what each role involves?
All three of my jobs are closely interlinked. Most of my time is spent caring for patients receiving treatment for blood cancers such as leukaemia or myeloma, including patients having stem cell transplants. As the Transplant Program Director I have additional responsibilities running the regional bone marrow transplant service and work with an excellent team of doctors, nurses and support staff who are very dedicated to their patients. As a Senior Lecturer I carry out research - my main interest is developing ways to make stem cell transplants safer and more effective.
You are the chief investigator on the Bloodwise-funded TRALA trial, for people with a type of amyloidosis. What are you testing in this trial?
We’re investigating a new way to treat AL-amyloidosis. AL-amyloidosis is one of a group of amyloidosis diseases: rare, serious conditions caused by a build-up of an abnormal protein in organs and tissues. The protein is abnormal in different ways for different types of amyloidosis. In AL-amyloidosis, the proteins are made up of ‘free light chains’ (FLCs), which are made by abnormal plasma cells (a type of white blood cell). Patients with AL-amyloidosis are often very unwell at the time of diagnosis, and the build-up of FLCs may have been happening for many months or even years before the patient develops symptoms.
The aim of treatment is to destroy as many of these abnormal plasma cells as possible so we can reduce or eliminate the production of the FLCs. This allows the body’s normal repair processes to work on removing the protein, allowing tissues and organs to recover, and is the same way that myeloma is treated. The problem is that patients with AL-amyloidosis tend to have worse side-effects from treatment compared to people with myeloma, including heart, liver and kidney problems.
In autologous stem cell transplants, stem cells are taken from the patient and frozen while the patient receives a high dose of chemotherapy, and then the stem cells are put back in the body. This treatment has been available to patients with myeloma for several decades. However, in patients with AL-amyloidosis, high dose chemotherapy has far greater toxic side-effects, which can lead to serious or even life-threatening damage to organs. In those patients that can receive an autologous transplant and survive, the amyloidosis responds very well. Unfortunately, only a small proportion of patients with AL-amyloidosis can be offered high dose therapy and transplant.
In the TRALA study we are attaching a radioactive ‘label’ to an antibody (a protein that can recognise other proteins), then infuse this through a vein to target radiation specifically to the bone marrow. The radiation destroys the plasma cells that are producing the FLCs. It should be possible to control the disease with this technique as well as or better than we can with chemotherapy. Because the radiation goes only to the bone marrow we also hope not to see any damage to other areas of the body. This may make autologous stem cell transplants in AL-amyloidosis much safer and we can then offer the treatment to a greater number of patients than we can do currently.
The TRALA study is operating over 5 sites around the UK. The treatment involves a close working collaboration between haematologists, radiopharmacists, nuclear medicine specialists and medical physicists, all of whom are important in delivering the trial successfully.
Members of the Southampton TRALA team (L-R): Matt Guy (medical physicist), Sandra Johns (nuclear medicine specialist), Julian Williams (nuclear medicine specialist), Clint Zvavmwe (radiopharmacist) and Gemma Lewis (medical physicist).
TRALA is a Phase 1 trial. What does this mean?
Clinical trials are divided up into several sub-types from small pilot studies through to Phase 1, then 2, then 3.
A Phase 1 study is designed mainly to look at any toxic effects of a drug or treatment (the ‘agent’), but we often look for a sign of response in the disease as well. To do this there are usually 3 or more different groups of patients who would receive different doses of the agent being tested in the trial. At the first dose level, a small amount of the new agent is used in 3 or more patients. If there are no serious side-effects and after the results have been reviewed by an independent team of experts, the trial progresses to a slightly higher dose of the same agent, and so on for perhaps 3 more dose levels. Once a serious toxic effect or side-effect has been seen in a patient, then the safe dose level can be set and the trial closed.
In a Phase 2 trial, many more patients are treated with the aim of revealing any rarer side-effects but also any possible disease response. A Phase 3 trial would be used to test the new agent against an established treatment to see if there was any improvement over the established treatment. This is the highest level of test and if a new treatment shows an improvement it could enter into regular use in medical settings.
As the TRALA study is a Phase 1 trial, we are testing three levels of radioactive label attached to the antibody in patients with AL-amyloidosis, before they go on to have an autologous stem cell transplant. We have already used the same technology in patients undergoing autologous transplants or donor transplants, but always with chemotherapy, so in TRALA this is the first time anywhere that a radiolabelled antibody alone has been used to prepare a patient for transplant.
Gamma image of one of the patients taking part in the trial (used with patient’s permission). Dark areas indicate places where there are heavy concentrations of radioactive antibodies. The radiolabelled antibody is binding to the bone marrow cells and plasma cells which are found in the bones of the back, the ribs, breast bone, pelvis and hips. There is also activity in the spleen, which can contain plasma cells. Importantly, there is very little sign of the radiolabelled antibody in other organs such as the liver, kidneys, bowel, heart or lungs.
Where are you in the TRALA trial at the moment?
We have completed the first (lowest) dose level and started to transplant patients at the second dose level. So far, there have not been any serious side-effects in the patients treated so we are continuing to recruit patients in order to complete the trial by the end of 2019. In total we anticipate treating 12 patients, 3 at the first two dose levels and 6 at the final (highest) dose level.
It is too early to say whether there are consistent disease responses but I can say that there have been very encouraging signs already that the treatment does have an effect on the disease. The best result would be a completely non-toxic way to transplant patients with AL-amyloidosis, which achieves disease response and helps organs to recover.
What does your work mean for people who have blood cancer?
Our work in Southampton and in other sites involved in our trials may mean that we can offer less toxic transplant preparation to patients but also potentially improve our ability to control disease and put it into remission. Our work with radiolabelled antibodies will help patients with AL-amyloidosis but could be helpful for patients who need transplants because of other blood cancers.
What is a typical day at work like for you?
The day-to-day pattern varies slightly but generally involves the care of patients on the ward receiving transplants or chemotherapy, clinics where I will see new patients or patients that have been transplanted and are recovering. I also seem to spend a considerable amount of time in meetings!
What's your favourite thing about your work?
Seeing patients in remission after a stem cell transplant or chemotherapy, who are getting their lives back to normal after undergoing the most difficult treatments. The courage of people never ceases to move me.
What's one of the hardest things about your work?
When our attempts to defeat a blood cancer fail and a patient relapses. Telling patients that they have relapsed is one of the most difficult aspects of my job and every case takes a little more out of me. We get to know our patients very well and it is always hard when treatments don’t go as hoped.
What do you do when you’re not at work?
My main interests are walking in the Hampshire countryside, gardening, and sailing, mainly around the Isle of Wight and the Solent. I enjoy competing in sailing races at the weekend!
Kim at the Cowes Week races in the Solent.
Is there anything you’d like to say to Bloodwise supporters?
A huge thank you to all the Bloodwise supporters out there – I keep an eye on the Bloodwise tweets (the only social media I use) and am amazed how many different ways people find to raise funds. There is no doubt that over the years Bloodwise has massively transformed the way in which patients with blood cancers are treated, with definite improvements in the survival of patients. Without Bloodwise supporters the huge advances in the treatment of these conditions would not have been possible. Keep it up, everyone!
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You can follow Kim on Twitter @orchak55.
We’ll be back soon with another day in the life.