 Hello, good morning. My name is Monique Minema. I work as a hematologist in the University Medical Center Utrecht in the Netherlands. And my talk will be about AL amyloidosis. And the main topics that I will present are first on the disease itself. AL amyloidosis is a very difficult disease to understand. So I would like all the listeners to understand really how their disease is originating from the bone marrow and how the proteins that are shattered by the plasma cells in the bone marrow are causing the amyloid deposits in your body. After that, I will talk a bit about the frustration many patients face in being diagnosed with this disease. Because for many patients it's a long road before this diagnosis is made. And that's frustrating to them. But I would like to explain to them why it's so difficult to think about this disease and also why it's so difficult to prove this disease and therefore give this diagnosis to patients. The last topic in my presentation will be about treatment. And treatment is vastly improving. So that's a hopeful message to our patients with suffering from AL amyloidosis. And the treatment is mostly improving because we have new treatments coming from the multiple myeloma field. Also comprising immune therapies. So now we have large clinical trials demonstrating that combination therapy with immune therapy in combination with chemotherapy is really improving the lives of patients. And I would like to discuss some of these drugs and also the side effects these drugs have. So that I think will be the biggest part of my presentation. And after that there will be time for some questions from the audience. So first, the origin of the disease. AL amyloidosis is one of the plasma cell discresias. One of the plasma cell monoclonal diseases. And that means it's a sister of multiple myeloma, angus or plasma cell leukemia. But it's a very different disease. So the plasma cells originate in the bone marrow and they shed a free-light chain in your bloodstream. But this free-light chain is so different from normal free-light chains that it has conformational changes. And that means that the protein is not doing its original job, but it's sticking to other proteins and forms fibrils. And those fibrils, they will attach themselves to certain organs in your body. And with AL amyloidosis, it's mostly the kidney, your heart and your nervous system, but also your liver, your bowels, your stomach, your lungs and also soft tissues can be affected by AL amyloidosis. And what happens when those fibrils stick to the outside of those cells, that will cause organ damage. So for your heart, for example, it means that your heart will enlarge. It will remain a powerful muscle for a long time, but it can't relax anymore. So your heart has difficulty relaxing and therefore you have edema in your body and also your blood pressure will drop and you feel very fatigued when you are doing an exercise or just walking up the stairs will be becoming much more difficult. And we call that heart failure with preserved ejection fraction. So that's very important. It's also a prognostic to patients. So when you have severe heart disease, your prognosis is much worse than when you have no heart involvement. The other one is the kidney. So the kidney can be affected and it's not that there's kidney failure, but mostly that there is a protein leakage from your kidney. So you have lots of protein in your urine and patients will notice that because they have a foaming urine and also edema when they look at their legs, they will be enlarged with lots of fluid in there. So those are the two most affected organs. But what's really difficult is that it's not always the same with AL amyloidosis. Sometimes the heart is not involved, sometimes the heart is involved, but also your bowels and your nervous system. So most patients have two to four organs involved, but in different combinations. So that's one of the difficulties to understand the disease for clinicians because it's not always the same. And in combination with that, it's also a very rare disease. So most clinicians never heard about amyloidosis before. So you have to think about it before you can diagnose it. And the other thing is that perhaps if you go to a doctor because you have complaints, normally you go to and you're sent to a medical specialist. We have medical specialists that have an organ specialty. So for the heart, you go to the cardiologist and for your kidneys, you go to the nephrologist. So they only look at one part of your body and they examine it. They don't think about it, about other parts of your body. But if you look at the complete picture, then you can see it's a systemic disease and it takes a time before the medical doctors see all the points together and then think about amyloidosis. And then the diagnosis itself. Amyloidosis means that you have amyloid deposits and in AL, it means the cause is a plasma cell clone in your bone marrow. So you acquire that disease during your life. But in most types of amyloidosis, it's hereditary. So you are born with a mutation and that's why you are forming amyloid deposits. So it's a completely different disease with a completely different treatment. Never give chemotherapy to a patient who does not have AL amyloidosis but another type of amyloidosis. So typing of the amyloid is of the utmost importance but it's very difficult. And not many pathologists can do it very good and that's why we have expertise centers in many countries in Europe and also in the United States. So that's also tricky. You diagnose the pathway, if a certain physician thinks about the disease, it's also very difficult to prove it. And the end result is that, for example, in the Netherlands, it takes most patients more than a year before the diagnosis is made. And that's important because if you are later in your diagnostic trajectory, then your outcome is worse because we treat the disease with chemotherapy. So if you have many complaints, if you're very frail, your heart is not functioning good anymore then also chemotherapy is very difficult to tolerate for patients. So that's why we think early diagnosis is one of the most important tasks be as expert centers have to educate our fellow clinicians. As once you're diagnosed, we make a prognostic score and then we see how we can treat you. And the most important thing to remember is that we can only treat living cells. So we can treat the cancer plasma cells in your bone marrow. We can't treat the amyloid itself. We don't have a nice machine that dissolves amyloid in your body. There's a lot of research on that and there's still clinical trials for that. There's no certain proof at this moment. So if you're not in a trial, your only treatment will be chemotherapy and most important drugs of that are, for example, Bortesimib, but we also give dexamethasone to patients and cyclophosphamide. And a new drug on the block is Daratumumab Darcylex. So that's immune therapy that's given sub-Q or intravenously and that's very effective. But importantly, that's also very well tolerated by AL-aminoidosis patients. So they don't have those massive side effects they do have with standard chemotherapy. So there was a big trial performed two years ago. It's called the Andromeda trial and that proved that the combination therapy of Daratumab together with Cyborg, that's the chemotherapy regimen, improves the hematological response rates in patients. And that means it proves that all plasma cells in the body of the patient will die and no more additional amyloids can be formed. The amyloid that's already in your body, it will stay there and only your own body can remove it. So you have special cells in your body that will remove it, but it goes extremely slow. So the only thing we can do is stop further amyloid formation by giving chemotherapy in combination with Daratumab. And the second thing is that we can do is help you deal with all the side effects. So give you diuretics or stockings or other drugs to help you with all the side effects but also the complaints that the disease itself gives you. And I think that will be the most important things in my presentation.