 Good afternoon. Welcome to the session on MRD. My name is Hans Scheurer. I'm the president of myeloma patients Europe, and this is the session on MRD for who not already knew what that means, the abbreviation MRD. It stands for Minimal Residual Disease, which is a term to describe the small number of cancer cells left after treatment. And why is MRD a hot topic in the environment of the myeloma and alamelodosis treatment developments? Well, from the perspective of patients and patient groups, the issues that we want to discuss are the following. So first, understanding MRD, it's discussed in the field as a new technique for measuring the remaining cells after treatment. So being part of the discussion as patient advocates and give input from the patient perspective, you need to understand what it is. The second aspect we want to highlight in the session is what can be the role of MRD in the clinical setting. We invited hematologist Hans Jacobs from the Radboud University in the Netherlands to make us understand what the challenges are and the new opportunities when measuring MRD is applied in the clinical practice. And the third one, MRD in regulatory perspective. What is the value of MRD data from the regulatory perspective? Is it a meaningful addition to define value of a treatment? Maybe even in an earlier stage. So the recommendation pathway could be shorter. We invited Paula von Hennig from the European Medicines Agency to guide us through this aspect since MPE patient advocates are active in the recommendation process of treatments. And they will be confronted with the MRD discussion over there. But before we dive in the deep water with Hans Jacobs and Paula von Hennig, let's start first from our position, our view as patient advocates of the myeloma and the AL amyladosus community. What do the new developments in MRD measuring mean for patients? So do patients understand what an MRD outcome means with regard to the status of their disease? And what is the burden of the MRD measuring for patients? Why is MRD a welcome innovation for measuring response? And is MRD in the sense of prognosis a reliable measuring point? And when the depth of the response on the MRD level is accepted as a surrogate endpoint, for recommendation, what are the pitfalls and what the benefits from a patient perspective? Well, understanding response categories, for years, we are familiar with the categories once described by the IWMG when defining their responses on treatments. And these are these ones. So shrink and complete response, complete response, all very good outcomes, very good partial response, mostly happy with that too, a partial response and a minimal response. And then we have a situation when a treatment is not able to push back the cancer growth, can be in state of no change or stable disease or a plateau. And the worst message just to hear from your hematologist is that you have progressive disease or relapse. And this will eventually happen to anyone relapse, but the better you respond to the treatments, the deeper the response is, the longer your remission period will be. So a deeper response is important. And to know how deep the response is gives a few on the remission time. You want to know that as a patient, it gives you a perspective on the quality of life. You might have the coming time and with or without treatment. Now, for decades, we know that a complete remission or better a stringent complete remission is excellent. But still there are myeloma cells remaining that are not detected. And these remaining cancer cells will come up again. You will need another treatment to get control over your cancer. So MRD, or measuring the minimal arrest disease, even when having complete remission, is therefore valuable information to see on a much more detailed level what the amount of the rest disease is still present in the bone marrow. MRD measuring techniques, that is the field of Hans Jacobs. And he can explain better than what I can do what is meant by that. But as patient advocates, it is at least important to understand the difference between two outcomes on MRD. That's the negative one and the positive one. So an MRD positive test result means that the disease was still detected after treatment. And MRD negative one is what you want to see. That's the result means there's no disease was detected after treatment. From a clinical scientific angle, the information MRD measuring provides is for sure an improvement in understanding the depth of the response, efficacy of a treatment for patients. But from the patient perspective, we are used to follow our disease with just blood samples, where the MRD measuring till now bone marrow punctures were necessary. Don't have to explain the unpopularity of bone marrow functions among patients. They hate it, OK, once a year maybe. But every control, no way. That's why MPE supports the transition of MRD measuring from bone marrow punctures to measuring in the blood, which would be for patients a very welcome improvement. Hans Jacobs will speak about this innovation and the opportunities for now and the future. So far, there's nothing questionable about MRD measuring developments now increasingly done in clinical trials to detect the depth of the response for new treatments. And in the nearby future also applied in the real world of the clinics for monitoring the rest disease on a very detailed level. The step to use MRD measuring techniques for following the development of the residual disease in a regular setting in the clinics is an improvement for patients because you could fine tune the moments to stop, pause, or start a new treatment. Much sharper than only wait for the symptoms, like sometimes it's done. And in an economical sense, treatment pauses are a new way of controlling disease, although you need to do this based on data, of course. And for example, we know that a drug like Daratumumab is active for about six months in the body of a patient. And for two reasons, it is a logical consideration to integrate a treatment pulse in the now described regime. From a clinical perspective, you enhance the efficacy because of de facto postpone the moment of refactoring of Daratumumab. And the second reason is that it's just saves money for societies. But to do this right, you need reliable data where you can base your decisions. And MRD monitoring is very helpful here. So the use of MRD measuring technique has a future in not only clinical trials for defining value of the treatment for recommendation pathways of the European Medicine Agency, but also for the clinic that patients visit for their controls and treatments. Looking at the value of the MRD data for the European Medicine Agency recommendation pathways, companies see an opportunity here for faster approval. MRD as a surrogate endpoint for early detection of a value. One of the focus of the patient group, because it oversees the whole group of patients, is that new drugs and innovations that are really valuable need to reach patients and not only congresses and scientific journals. Is it possible to use early flex-like MRD for approval of new treatments? An early point of enthusiasm of even a point where we can base an approval for market authorization? Well, the European Medicine Agency has three pathways of expedited approval. Accelerated assessment, conditional marketing authorization, and PRIME, which stands for Priority Medicine Scheme. And the FDA in America has four pathways, FALSTRAC, Accelerated Approval Priority Review, and Breakthrough Therapy. The exact differences between these options are not that important here to explain, but the pot meters to reduce time and accelerate, the procedure are aligned in an early stage. During the development of the product, shorten the review process with a few months or accept surrogate endpoint like MRD, a flex that could be early predicting the value of the drug. And how do we look to these options to accelerate from a patient group perspective? Well, the opportunities seem clear. Faster access to novel treatments is what we want, especially patient groups with myeloma, where the continuation of your life depends on having next options when refractory to former used treatments starts. And how does the European managing agent value MRD data as a base for recommendation of a new treatment? Speaker Paula von Hennig will touch upon that from the perspective of the regulator. And for us as patient advocates, it is on one hand important to understand what the value of MRD measuring is in the clinics, but also to what it can lead when MRD is accepted as a value argument for approval of a new treatment. We have one concern here, besides all the beneficial aspects, when the depth of the response, and I mean the amount of MRD negative data the clinical trial will show, is the new targets will this lead to the development of more aggressive therapies just to reach the status of approval based on as much as MRD negative patients as possible. Of course, the depth of the response is one thing, but for patients who will have a future of many treatments after that, two other aspects are also important. And that is the remaining quality of life and the options that will be still available in a later stage. When you, for example, develop a four or five can be even for the induction stage of after first relapse, you might get an impressive amount of patients that respond low on the MRD scale, MRD negative. But you are using a group of treatment options in a combi where you could create in a much earlier stage resistance for options. So the depth of the response might be impressive. The remission period might be longer for this treatment, but eventually the disease will relapse and do you still have the other options available then? Same question you could ask when treating patients in the smoldering stage with linoleumite that's comparable. You could postpone the development to myeloma with it, but you might also make these patients earlier resistance to linoleumite, a nasty dilemma for sure. For patients, it is therefore important to have MRD data linked to the effect on the quality of life. And the overall survival. MRD data alone only show the effect of the treatment, but not the price the patient pays for it. So we might come back on these in the discussion later. The opportunities and the challenges may I now hand over the screen to the next speakers, which I'm proud that they contribute to this session to get grip on the MRD topic. First, Antja Kops, amatologist from the Radboud University in Netherlands and the second speaker, Paul van Henig, from the European Medicine Agency. I hope you will enjoy this session. If you have questions, we will have a Q&A discussion following the presentations. Thank you for listening. Dr. Jakobs, the screen is yours.