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Skip to 0 minutes and 13 seconds GUY PRATT: I’m Guy Pratt. I’m a consultant haematologist at the Queen Elizabeth Hospital in Birmingham. My main interest is in malignant haematology. So it’s multiple myeloma and chronic lymphocytic leukaemia.

Skip to 0 minutes and 33 seconds There are a number of B-cell tumours. So in adults, chronic lymphocytic leukaemia is the commonest leukaemia in adults. And it’s usually a very slow and indolent leukaemia, which is treatable. But unfortunately, it’s not curable. So there is an unmet need for those patients. In children, the commonest leukaemia is acute lymphoblastic leukaemia, which is obviously very relevant to what we’re going to talk about in a minute. And most children are cured with that leukaemia. But there are probably about 10% of children where, unfortunately, their disease hasn’t been able to be cured. There are a number of other B-cell malignancies. You can get acute lymphoblastic leukaemia in adults, where the prognosis is actually quite poor.

Skip to 1 minute and 31 seconds So there’s an unmet need for those patients. And then, most non-Hodgkin’s lymphomas are B cell in origin. And there are a wide variety of different lymphomas. I won’t go into the detail because they’re very variable in terms of their prognosis and outlook.

Skip to 1 minute and 57 seconds The first trials in CAR therapy were in children with acute lymphoblastic leukaemia in Philadelphia, in the States. And these children had a disease, which had not responded to previous therapy. A number of them had transplants. So their outlook was extremely poor. Subsequently, it’s been used in adults with ALL and adults with chronic lymphocytic leukaemia. And I think there’s one case report of it being used in myeloma as well.

Skip to 2 minutes and 36 seconds The responses in children with ALL who’ve been treated with CAR therapy’s been really amazing. Responses of 80%, approximately, have been seen. And many of these responses have been durable in at least half the patients. Importantly, the responses have been so good that it’s allowed some of the children to go on to have a bone marrow transplant from a donor, which is obviously a curative approach. This response rate’s not been seen with any other form of treatment. And I think it’s groundbreaking that this is being seen with this approach.

Skip to 3 minutes and 30 seconds One important point is the potential toxicity of the procedure with CAR T-cell therapy. You can get a very profound, immediate inflammatory response. And a number of patients who’ve been treated with CAR therapy have actually required intensive care immediately after the infusion of CAR T cells. This is called the cytokine release syndrome. Thankfully, we are getting better at treating that. It’s recognised that you can give various anti-inflammatory treatments that can improve the care of these patients. But it is a side effect that is of concern and will need to be monitored, particularly when you’re treating newer groups of patients with this therapy, when it’s less clear how bad their problems might be.

Skip to 4 minutes and 31 seconds Other toxicities are that you affect the normal immune system so you produce antibodies less well following treatment. And a number of these patients need to be on antibody replacement later on.

Skip to 4 minutes and 51 seconds I think there’ll be an explosion in trials with CAR cell therapy, not only in leukemias, but solid tumours as well. So it’s a very exciting time. I do think we have to be aware that there are several barriers. It’s very expensive. Practically, it’s not always straightforward. And I think in the UK we’re probably a bit behind America in terms of the practicalities of doing it. But undoubtedly, we’re going to have trials in the UK for patients. It is expensive, so it will have to go through the regulatory bodies [INAUDIBLE]. For example, NICE will have to approve funding if it does become shown that it’s of value in the UK.

Skip to 5 minutes and 44 seconds One important point is that clearly this is a very new area and a lot more research is required. In particular, what is the best target for these immune cells? And we have to be very careful because the problems that we’ve seen with the inflammatory response could be more marked if you are targeting the wrong antigen for example. The other issue, of course, is that not all patients respond. And patients can relapse despite this CAR T-cell therapy. So there needs to be a better understanding of why these patients relapse and what we can do to try and improve their outcome.

Engineering T cells to attack leukaemia: a haematologist's perspective

In this video Dr Guy Pratt, a Consultant Haematologist and Senior Lecturer in Haematology, reflects on the impact that T cells genetically modified to recognise cancer are having in recent clinical trials in patients with blood cancer.

Reflect on this new type of therapy and share your thoughts with other learners in the comments area.

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This video is from the free online course:

Cancer Immunotherapy: a Step Change in Cancer Treatment

University of Birmingham