Hope for patients with beta thalassaemia as new gene editing therapy rolled out at UCLH

A UCLH patient with beta thalassaemia has spent her first ever Christmas without needing to plan her life around blood transfusions after a gene-editing therapy has left her able to produce her own red blood cells.

Kavita Mehta has transfusion-dependent beta thalassaemia (TDT), which means she does not produce enough haemoglobin, the protein in red blood cells that carries oxygen round the body. This means she usually has to have a blood transfusion every three weeks.

Beta thalassaemia has left her severely tired, weak, and short of breath. Apart from having to travel to hospital every three weeks for a day of blood transfusions, the transfusions themselves can lead to an accumulation of iron in the body and cause damage to the liver, heart and other organs. This often leads to various medical problems such as diabetes, poor bone health, severe infections, liver damage or heart failure.

“A life of regular blood transfusions is all I know. I cannot believe that doctors have already seen signs that I am now able to produce my own red blood cells. I can’t tell you what this means to me, and to my family who have had to watch me go through this and care for me. And more than anything, I am thrilled that this drug is available on the NHS and may help patients who are much younger than me live a life independent of transfusions,” Kavita said.

Kavita, 36, was diagnosed with beta thalassaemia when she was just a month old. “We were living in Kenya at the time. My grandmother noticed I looked unusually pale, my mum took me to hospital, and that’s when they found out. My parents are both carriers and so is my brother. I started transfusions straight away. I can’t remember how many bags I needed, but from the beginning it was every six weeks, without fail. That carried on for years.

“When I was five, I began iron chelation. That was the hard part. The needles back then were awful – huge butterfly needles – and my poor mum had to give me the injections every night.

“Growing up, we travelled constantly because my dad worked in finance and moved around a lot. I have lived in ten different countries. Every time we landed somewhere new, my mum had to sort out a hospital for me. In some places she even had her own donor list because she didn’t trust the blood supply – understandable in parts of Africa and India. When we lived in Jakarta, we had to fly to Singapore for my transfusions. When we lived in Russia, we’d fly back to England. It was relentless: every six weeks, then every four, and now it’s usually every three to four.

“For me, it was normal. The injections, though, were the worst. Iron chelation used to be a slow ten-hour overnight infusion. Five nights a week. It dictated everything – my weekends, school mornings, even nights out when I got older. Sometimes I’d get back at 2am and still have to set myself up for the infusion, then wait until midday to take it off. Sharing a dorm room or a flat with housemates made it all feel even stranger.

“The transfusions themselves were fine. You sit, watch TV, get on with it. The worst bit was finding a vein. Growing up, that terrified me. I’d get so anxious that my veins would constrict and make it even harder. My record was seven attempts in one session. Here at UCLH, though, it’s been amazing. This is the longest I’ve lived anywhere, the nurses know me, and I feel much more settled.”

Last year the NHS became one of the first health systems in the world to use the therapy called Casgevy, for beta thalassaemia, which mainly affects people of Asian, Mediterranean, and Middle Eastern descent.

Casgevy uses the patient's own stem cells which are removed, edited over a six-month period so they produce haemoglobin, then reintroduced into the body via infusion. In international clinical trials the technique removed the need for blood transfusions for at least a year in 98% of patients.

Kavita received four phials of the drug in November in a procedure which took three and a half hours. She spent six weeks in hospital, being monitored and cared for as her body worked to accept the edited stem cells. She was discharged in mid-December, just in time to spend Christmas at home with her family, and is now continuing her recovery at home.

UCLH haematology consultant Ben Carpenter, who has been treating Kavita, said:

“We are pleased with the way things are going for our first patient. She had a challenging time in hospital but is now feeling much better.

“It has been more than two weeks since Kavita's last red cell transfusion, and her levels are continuing to rise independently. We are now seeing normal red blood cells being produced by her own bone marrow for the first time since she was born.”

The hope is this will provide a cure for many patients with TDT, preventing life-threatening complications and improving their quality of life. Previously the only effective cure for thalassaemia was for patients to have a stem cell transplant.

But there is a national shortage of donors, and the procedure can also cause complications where the recipient's body rejects the donated cells or suffers the severe complications which can transpire with a new immune system.