 Hi, I'm Mohamed Moti from the Sorbonne University and Saint-Antoine Hospital in Paris, and it is my great pleasure to be with you today as part of this lovely masterclass. For this session, I've been asked to address some of the issues we have faced during this COVID-19 pandemic in the field of the management of multiple myeloma. Here are my disclosures. Let me start first by highlighting the importance of the risk of COVID-19 infection in patients with multiple myeloma. In order to highlight this, I wanted to share with you a clinical case. This is unfortunately one of our first COVID-19 infections in multiple myeloma in my department during the first wave. This is a 63-year-old gentleman with myeloma diagnosed in 2017. The patient received his transplant eligible, so received standard induction with VRD, Bortezumablenadomidexametazone, four cycles, achieved VGPR. We performed a stem cell collection. We performed the transplant. The patient was in VGPR, and he was then receiving maintenance with the linalidomide. The patient relapsed two years after transplant, and he was included in a protocol, the ikema protocol. This is the combination of esatuximab, carfizumabendexametazone, and since then, I think we have already had the communications about the results of this trial. He actually achieved CR. In April 2020, the patient presented with Pneumonia. He needed very quickly ICU intubation, and despite the treatment with stocillizumab and, of course, supportive care, he died a couple of weeks later. So you can see how difficult, how tough, and how quick this can be. So this is why very rapidly we have summarized our experience of COVID-19 in hematologic diseases, because we wanted to alert the broader community about the risk in this population. And we have published very quickly our first 25 patients with COVID-19 infection. And what you can see, and I have underlined this in red here, that out of 25 patients, the majority were multiple myeloma patients. And there is a good explanation for this, because multiple myeloma patients are highly immunosuppressed by the disease itself, because the immune response is impaired. But multiple myeloma patients are also relatively elderly patients, frail patients with comorbidities. And also the treatments we give to multiple myeloma are inducing a high level of immunosuppression. And this is about dexametazone. And we know very well that the high dosage of dexametazone is extremely deleterious. And this is why the mortality rate of COVID-19 in multiple myeloma is significantly high, around 30%. And this has been confirmed now in studies from Spain, from Italy, from the UK. You can appreciate here, for instance, in this very large series, patients who are elderly, who have hematological malignancies, and especially myeloma is highly represented, unfortunately, are the patient with a high risk of COVID-19 severe infection. So this was a very important message that needs to be clearly communicated and highlighted. Now, having said this, what was and what is the impact of the COVID-19 pandemic on the management of these patients? And since the early days of the pandemic, I think most hematology centers in Europe and worldwide and in my department, we have established some objectives, some goals. First objective is to protect the highly immunosuppressed myeloma patient, because I've just mentioned the high risk of mortality in these patients. But at the same time, we wanted to maintain a high standard of multiple myeloma care. We wanted to continue to deliver the optimal treatment for these patients. And in parallel, you wanted to protect your healthcare professionals, because you need these highly skilled manpower to deliver the optimal care to your myeloma patient. So the practical questions we have faced were about whether we should postpone frontline auto transplant for myeloma patients, because the problem with auto, as you know, is about the eplasia, and that is further worsening the risk. But also, some patients during auto may require ICU bed, and the ICU is extremely busy with the COVID-19 patient. So you have to think about how to handle this and what are the alternative options. Also, stem cell mobilization can be an issue, because you have to come frequently to the hospital. And then, of course, circulation would increase the risk of transmission of the virus. Also, you have patients receiving maintenance therapy, and probably this is contributing to the immune suppression. So should we modify this? And immediately, we also acknowledge the deleterious role of dexamethasone. And the question is how to handle this? Should we reduce the dosage? Should we discontinue? And in which patient? We also know that many myeloma patients receive bifosphonate, and they come frequently to the hospital. How to handle the use? Of course, we were all asking the question whether we can do something in a prophylactic way to protect myeloma patients against COVID-19. But as you may guess, this is very tricky, because it is now still not yet well-established. Of course, the management of these patients, but last but not least, how are we going to handle the clinical research protocols? Because clinical research protocols do require a lot of visits to the hospital. And again, lots of circulation, lots of traveling. And more circulation, more traveling, definitely the risk of infection is very high. This is why we and others have clearly thought and published some recommendations to answer these questions. When it comes to autologous stem cell transplantation, we thought that we can postpone the procedure, especially by increasing the number of cycles of induction. And we knew that there is no harm to the patient, because actually in terms of overall survival at the end, that may not create a problem. Also, we know that by giving more cycles of induction, actually, you are deepening the response. So again, there is no harm. It's more about benefit. However, in the high-risk cytogenetics patient, we thought that this should not be delayed. So you can see how this has been personalized. Standard risk, you would increase the induction regimens in the high-risk, no delay. And of course, immediately we established the practice, we recommended the practice that we need to test frequently these patients. And when it comes to the transplant approach and the way to handle transplant safely in this environment, the EBMP, the European Group for Society for Blood and Marrow Transplantation, very quickly delivered and published some consensus recommendations that were adopted, I think, worldwide. The prevention policies, how to manage the staff, because of course, you're worried about the patient, but also you want to keep your staff in action and, of course, avoid lots of sickness and infections. We had also a recommendation about the outpatient visits and visitors, because again, the message is that the virus is circulating with people. So we had to protect the patient. This is why we needed to take some tough measures, very difficult from a psychological point of view, because patients would become a little bit isolated in the different departments. But definitely we had to unite forces and deliver these messages and these recommendations. When it comes to the steroids, especially dexamethasone, I think we have taken the decision and there was relatively good consensus that you need to consider reducing the dosage or even discontinuing, especially in the patient who are in excellent response or even complete remission. And then we would say, well, these patients, maybe you can avoid dexamethasone and it's a way to avoid further increasing the immune suppression. And actually, this requirement mandated by the pandemic proved to be a good bet, because we know now that actually maybe we are using a lot of dexamethasone in multiple myeloma patients and maybe the patient don't need such high dosage, because dexamethasone is a major risk for complications in the patient and our patients are suffering a lot from dexamethasone. So I think this is a positive aspect of the COVID-19 pandemic where now we are able to rethink the dexamethasone dosage. When it comes to the outpatient visits, we had to be very strict to protect these patients. It's about the benefit and risk ratio to avoid transmission of the virus. But we also pushed in order to push pharmacists to deliver multiple, several weeks and months of treatment. We favored, we pushed to favor home hospitalization, home care, and whenever possible, switching from IV or subq to oral treatments. And when it comes to B-phosphonate, actually home administration or even delaying or temporary interruption were recommended. For clinical trials, of course, those who are really already enrolled and in need, I would say business as usual, we continue. However, for those patients, for the follow-up, for instance, it was clear that you have to open for teleconsultation. Avoiding the circulation, you had to deliver at home the different treatments. So everything has been recommended in a way to decrease the risk of infection. And I think these measures were rapidly adopted and they proved to be quite successful because the incidence of the infection decreased. And that's really a good news. When it comes now to the management of the patient with myeloma and who, unfortunately, despite the different measures developed a COVID-19 infection, well, obviously, the European Myeloma Network published some guidelines. They are summarized here. And this actually at the end of the day is more about symptomatic management because we don't have a curative treatment yet for the COVID-19 infection. Although now we know that vaccine is highly recommended and we do recommend vaccination to everybody. Although the immune system of a myeloma patient is more fragile and not all patients will respond very well to the vaccine, but definitely vaccination is highly recommended. Otherwise, the management in case of a severe COVID-19 infection is similar, I would say, to other patients with COVID-19. And of course, you have to hold the myeloma therapy while if you are struggling with a severe COVID-19 infection. Also, and I would like to conclude on this, we know today we have more and more knowledge about the COVID-19 infection. And we know it shares some similarities with the pathophysiology we know in different hematologic malignancies about clotting, about the CRS, the cytokine release syndrome and so on. So actually, we in the hematology in myeloma field, we were able to connect the dots and that has been extremely very useful to all of us. So in summary, as you noticed, I think this COVID-19 pandemic, when it comes to multiple myeloma patients, but to hematology patient management in general, significantly impacted clinical practice day to day. We needed to establish big adjustment. They are already now implemented in hospitals and clinic. And depending on where you are, whether you are still in a wave or you are in a sort of a post pandemic, definitely some of these measures will continue. For instance, teleconsultation is now here to stay and this is good news and much enjoyed by many patients to avoid traveling, to avoid transport, public transport, et cetera. Also, we should not forget about the dissemination of knowledge. And this is really great news. I remember during this COVID-19 pandemic, thanks to all of these digital and virtual tools, we were able to have lots of meeting with patient advocacy group and to keep the contact and to explain what's ongoing and to reassure because obviously what happened is that the pandemic generated a lot of anxiety, lots of fear. But for us also in the healthcare system, the healthcare professionals, we have adjusted our approaches. We have now our multidisciplinary meetings being handled in a virtual fashion. Of course, this is good news because it allows more people to meet and discuss the cases. So you have to see, and this is my philosophy to be always optimistic, to see some good news. And for instance, when it comes to the digital and rapid spreading of the knowledge, we immediately organize some webinars. This is one example of the webinar we organized very early with Professor Marie V. Mateos and it has been viewed by thousands and thousands of people on YouTube, but definitely we needed to connect all together. And we are, we need to be thankful and we need to acknowledge all of these digital tools. So as you may guess, this has been difficult. It didn't finish yet. We need to continue to be careful. We need to get vaccinated. We need to spread the word. But definitely this is, this pandemic has been a challenge like no other. Thank you very much for your attention.