 Hi, my name is Charlotte Poolin. I'm a hematologist from the Royal Marston Hospital and the Institute of Cancer Research in London. I'm here at the Myeloma patients Europe masterclass in Dubrovnik 2023. And I just spoke in a session around car T-cell therapy, so chimeric anterior receptor T-cell therapy for myeloma patients. So the session covered a little bit about how we make car T-cell therapy. So the fact that we're trying to engineer a patient's T-cells to be able to recognize the myeloma cells better. So they're then able to see the myeloma cell as something to be destroyed. And we do that by harvesting T-cells from patients and then genetically modifying the T-cells so that it's able to recognize the myeloma cell surface. And this process takes a couple of weeks. That's T-cells need to be manufactured. So from a patient point of view, the first thing that will happen is that the patient's T-cells are harvested. That's done like a blood test. And the T-cells will then go away to be manufactured in this way and engineered to be able to recognize the myeloma cell. During that time, the patient may need some myeloma therapy. So if the myeloma is progressing quite quickly, then we may need to deliver myeloma specific therapy in that time. But some patients are able to wait during that manufacturing time until the product is ready. Patients are then admitted to hospital and have some conditioning therapy before the T-cells are re-infused into the patient around five to seven days after the conditioning therapy starts. And then they'll stay in hospital for a period of a couple of weeks usually after that time until they're recovered enough to go home. And the reason that in hospital is so that we can carefully monitor for some of the common side effects of car T-cells delivery. So we're looking out for something called cytokine release syndrome, which is where the patient immune system has effectively become very overactive and caused a lot of inflammation. Usually we can manage that very well on the ward with paracetamol and fluids and sometimes a specific drug called tosylizumab, which helps to calm down the inflammation and sometimes with steroid treatment as well. But a few patients around 5% in some of the trials will need a bit more intensive support than just being on the ward and will need to be close to an intensive care unit in case that's needed. A small number of patients will have neurological side effects after the CRS is called ICANS. And so this is something that sometimes needs input from either intensive care or neurologists. But it's usually easy, easily managed either on the ward or with more intensive support. We're also looking out for infections and other things that are happening around that time and making sure that we treat those quickly and keep patients well and then able to go home and be discharged from the hospital after that. So I talked a bit about the two CAR T cells that are approved in Europe, so IDA cell and SILTA cell. And we went through some of the data from the initial trial, so the CARMA1 trial and CARTITUDE1 trial. And then we also talked about some of the more recent data that was presented at the American Society of Hintology just before Christmas. Looking at using these CAR T cells in earlier lines of therapy, particularly in patients who are perhaps relapsing early after their very first initial therapy. And we're seeing really excellent responses both in those patients who've had lots of prior lines of therapy and also in these patients that earlier lines of therapy and in randomized control trials compared to standard of care in patients who've had a few lines of therapy previously, we're seeing much better and longer responses for patients than the standard of care or the other treatments that would be available for them at that time. So we're seeing really excellent responses in patients who are then able to stay in remission for a long period of time. We're looking now even at using CAR T cell therapy in frontline therapy. So these are trials that are ongoing at the moment, but we're, you know, hoping that as we bring the treatment for earlier in the lines of therapy for patients, responses and duration of responses will be even better than we're seeing at later lines of therapy. We talked a little bit about the use of CAR T cell therapy to treat AL amyloidosis as well. There is less data in this space than in the myeloma treatment pathway, but we have several studies looking at using CAR T cells in amyloid. Essentially, we're trying to do the same thing. We're trying to engineer a T cell to target the abnormal plasma cell that's producing the proteins that misfold in AL amyloidosis. And so there's every reason to hope that the CAR T cells will be as effective at getting rid of those abnormal plasma cells as they are in the treatment of myeloma. And in the small series of patients that have been treated so far, that seems to be the case. And so there's lots to be optimistic about in the treatment of AL amyloidosis as well.