Beyond the median

It’s been five years since I was diagnosed with mantle cell lymphoma (MCL). I’ve always wanted to know what to expect from treatment. In 2014 the general consensus among haematologists was that the disease was treatable, if incurable. Depending on which research you read, the median survival time from diagnosis was somewhere between 3 and 7 years. Of course, median survival times tell you little about your own prospects. You always hope that you will be on the side of the survival curve that’s beyond the median.

The good news for MCL patients is that the median survival time is continuing to rise as new treatments are developed. I’ve recently read two interesting pieces of research. The first is a retrospective study of patients treated between 2000 and 2014¹. The survival graphs that are directly relevant to me are reproduced below.

OS and PFS in MCL patients younger than 65

For patients younger than 65 years old who had a stem cell transplant following chemotherapy, these charts show that the median overall survival time was around 13 years from first treatment, with the first 7 years likely to be disease-free. Subsequent treatments become much less effective however – hence the rather gloomy sounding subtitle to the study.

The second study concerns an innovative trial for MCL using CAR T therapy. This type of treatment was covered by the recent War in the blood documentary. CAR T therapy involves genetically re-engineering blood cells (T cells) so that they selectively target cancer cells and kill them. A paper² will be presented at the American Society of Hematology’s annual conference in December reporting on the progress of the Zuma-2 trial. The conference abstract states that of 28 patients who received the treatment, progression free survival after a year was 71%.

It’s significant as many of these patients suffered multiple relapses and had hard to treat variants of the disease. CAR T is not yet a cure and there were some pretty severe side effects (‘mostly reversible’), but it does seem like progress. More patients have now been treated on the trial, so it will be fascinating to see the updated results in a year or two’s time.

¹ Kumar, A., Sha, F., Toure, A. et al. Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: progressive shortening in response duration and survival after each relapse. Blood Cancer J. 9, 50 (2019)

² Wang, M.L. et al. 754 KTE-X19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy, in Patients With Relapsed/Refractory Mantle Cell Lymphoma (MCL): Results of the Phase 2 ZUMA-2 Study. (2019)

War in the blood

Every so often the BBC produces something that is worth the year’s licence fee alone. War in the blood, first broadcast last Sunday, is one such programme. It’s a truly remarkable 100 minutes of television.

I’d originally decided not to watch it. Somehow, it all felt a bit too close to home. The CAR T-cell therapy covered by the programme shares some similarities with the stem cell transplant I went through last year. Blood cell harvesting, long hospital stays and (ouch) bone marrow biopsies. The emotions you go through as treatment is explained to you and your carer. The periods of relative wellness, followed by total reliance on medical staff. It’s all horribly familiar. But encouraged by friends on one of the MCL forums I belong to, I decided that I needed to see it for myself.

Blood centrifuge
The blood centrifuge I was hooked up to a year ago. You see these being used in the documentary harvesting the blood cells needed for CAR T-cell therapy.

The personal stories of Graham Threader and Mahmoud Kayiizi are at the centre of the documentary. Both had acute lymphoblastic leukaemia (ALL) which had stopped responding to conventional chemotherapy. The phase 1 CAR T-cell trials they signed up to were their best chance – their last chance – of a long lasting remission. Phase 1 trials are inevitably risky undertakings, as they’re the first time new treatments are tried in people. But as Graham observed, “someone has to go first”.

The science behind CAR T is explained in a straightforward manner using ping-pong balls by Dr Martin Pule. He’s in charge of programming the blood cells used so that they attack the cancer and kill it. His early passion for tinkering with electronics eventually led him into this career. There’s a point in the programme where he talks about the data from the trials being all important. In the midst of the patients’ personal stories this made me gasp, but of course, he’s right. You have to remain objective to make the right design decisions for the patients. You think with the head, not the heart.

Dr Claire Roddie leads the teams administering the trials. The documentary gives a fascinating insight into what motivated her to become a haematologist, and she shares in the patients’ joys and sadnesses. You see the wider NHS at its best as well.

War in the blood is available on the BBC iPlayer for another month. It’s compelling viewing, with a bittersweet conclusion. I’m glad that I watched it. The future of all blood cancer treatment may well be CAR T-cell shaped soon. I’m grateful to the pioneers – the patients and medical professionals – for their selfless commitment.