 Good afternoon, everyone, and welcome to this webinar on COVID-19 vaccines for myeloma patients. My name is Ana Vallejo. I'm the myeloma patient group communications manager, and I will model this webinar today. First of all, I would like to thank you all for joining us today. As you know, COVID vaccination has raised a lot of questions, and especially around patients, about what is the best vaccine for patients or how COVID vaccines might affect myeloma and elamines treatment. MP has developed a Q&A on COVID vaccination that you can read on our website, and we hope that we can solve some of your questions during this webinar. Before we start, just for your information, just mention that this webinar will be fully recorded and will be uploaded to the MP, to the myeloma patient group website, which is www.npu.org, and it will be also available in our YouTube channel. Before we start, I would like to make a small summary on the webinar's agenda. The webinar is scheduled, as you know, from five to six, so the presentation will last about 40 or 45 minutes, and then I will open the session for questions. There are two ways in which you can ask questions to the doctor. One of them is using the microphone in your computer, as I'm doing now. Just press the right hand button that you will see on your screen. I will unmute you, so you can ask the question directly to the doctor, and the other possibility is to do that in writing, in the question and answer window. I will receive those questions, and I will read them to the doctor, so she can answer them. As you know, the talk will be given by Dr. Ana Sureda, head of the Mathology Department at Instituto Catalon de Oncología in Spain, and on behalf of MP, Dr. Sureda, I would like to thank you for your collaboration, for your time preparing and giving this webinar, and for summarizing for the patient community the most important updates on the approved COVID vaccines in Europe. Thank you very much for helping us always with these kind of activities, and the floor is yours. Thank you very much, Ana, for this kind introduction. First of all, I would like to thank MP, and especially you, for inviting me to participate in this webinar, which I think it's not so easy, because unfortunately, when we talk about COVID-19 vaccines in multiple myeloma, and of course in other hematological malignancies, probably we have more questions than answers, even nowadays. So I'll try to give an overview on COVID-19 infection, and basically I want to highlight some aspects that at the end will lead us to discuss COVID-19 vaccines in patients with multiple myeloma. So let me see if I can share the screen. Sure. Okay, is that okay? Yeah, it's fine now. Perfect. Thanks so much. So that's the title of my presentation, and of course, as Ana has said, we will be able to have some minutes for Q&As after the presentation, and here you have my disclosures. So here you have the agenda for the presentation. I'm going to introduce you a little bit to the respiratory viruses in hematology and what they represent for us. Of course, I will be discussing then the introduction of SARS-CoV-2 COVID-19 infection, the clinical impact of this viral infection in hematological malignancies in general, and of course in patients with multiple myeloma. And then I will be going into seroconversion to SARS-CoV-2 infection, and then, of course, the vaccination plan in oncohematological patients with a specific mention to multiple myeloma. So let's start with respiratory viruses. And here in this slide, I have tried to put hopefully quite a comprehensive list of the different viruses that we can eventually find in our patients. So the first group is basically a DNA virus, and here I'm sure that you can recognize some of them. Herpes simplex virus belong to this group, varicella sorters, CMB, EBB, and other herpes virus 6, 7, and 8. And we have to recognize that basically the first infection when we talk about these viruses, it's happening during childhood and in young adults, and usually disease comes because of an endogenous reactivation, and it's very infrequent to have exogenous re-infection. This is completely different from the situation that we see when we talk about community respiratory viruses, and here you have flu, metanomavirus, rhinovirus, enterovirus, coronavirus, and we will be discussing quite a lot about it. And here we never have an endogenous reactivation, and it's usually an exogenous infection. So that's another way of looking at these different type of viruses. And so when we think about community respiratory viruses and we think about the different type of hosts that we can have, so if we look at adult people that are not immunosuppressed, we have to say that the period of viral excretion is really quite low, that the viral load per drop is also quite low, and this is quite different from what we can see here in immunosuppressed adults. So basically patients with hematological malignancies and multiple myeloma. Here the patient can be eventually excreting the virus for many days, eventually for several weeks, and the viral load in each drop is quite high. Basically the infection in many cases, here in the non-immunodepressed adults, is being produced through the hands, although also it's related to the inhalation of respiratory drops. And if we look at children, so children, non-immunosuppressed children are basically characterized to have multiple and very close contacts, and they also present with a high viral load in each one of the drops. So basically immunodeficient patients and children's are the most effective ones. And in this slide, basically you can see the number of patients that have positive samples with respect to SARS-CoV-2 since the time of diagnosis, and probably this is being better seen here in this graph that basically represents that when we talk about immunocompromised cost, so basically looking at patients with hematological malignancies, the viral load is higher, and basically the peak is a little bit later than the development or the peak of the symptoms. And then this area under the curve, which is basically this area that I am showing here with the pointer, is really very high if we compare it with the immunocompetent adults. And that's one thing that we have to take into consideration. Another important thing to take into consideration, and these graphs have been taken from a paper that was published several years ago by José Luis Pena, who is a hematologist working in one of the hospitals in Valencia, and he was basically looking at the community-acquired respiratory virus. So the hospital admission rate, which was directly related to respiratory virus, was 22%, and the overall mortality was 18% in the population of hematological patients that he was looking at. So that's another important thing to take into consideration. And I'm not going to go through all the different risk factors that immunocompromised hosts have to develop this community respiratory virus infection. But as you can see, I mean, there are quite a lot of them that also have an impact in the disease progression to lower respiratory tract infection, basically lymphopenia, all the rage, smoking, for transplant patients have those TBI, the type of donor allogeneic stem cell transplantation. And of course, there are other factors that are associated to mortality related by these viral infections. And finally, I mean, to end up with this part of the presentation, and as I have basically been mentioning a little bit before, we have to take into consideration that there is a mortality which is related to the development of all these viral infections. As you can see here for coronavirus, for rhinovirus and metanomovirus. So that's a kind of a very quick summary of what we were working with in terms of respiratory virus when talking about patients with hematological malignancies immunosuppressed patients, but not very far away ago. We had what I have called here the tsunami COVID-19. So what's SARS-CoV-2? So basically it belongs to the coronavirus family. And coronavirus family, it's a very large family of viruses that can cause illness that has really quite range in terms of signs and symptoms. And it can go from really a common cold which does not have any clinical significance to producing severe disease. It's a better coronavirus and the natural reservoir are bats and the final hosts are humans and eventually horses. If we look at some biological characteristics of SARS-CoV-2, I want to highlight that this RO index that basically represents the average number of people that can be infected by each sick person is around three between 2.5 and 3.5. And if we compare it with the seasonal influenza, it's really significantly higher. The transmission is basically through big drops. And so this is why we have, let's say, to keep this security distance. There has no fatal transmission being described. And it has also been described some fecal oral transmission, but basically it's a respiratory transmission. From a clinical point of view, we can separate the infection into three different stages. The first one basically is characterized by some clinical symptoms of signs which are related to the viral response rate. But then we continue with the stage two and the stage three, that it's basically the pulmonary phase and the hyper inflammation phase that it's associated to the different clinical characteristics of this type of infection, which is quite different from what we knew from prior respiratory viruses. As you know, COVID-19 pandemic basically emerged in Wuhan, which is in the province of Hubei in China, and that was the late December in 2019. And here I have highlighted some numbers that it's very clear and this slide, it's a little bit old, which are completely outdated nowadays. The most important thing is that really very quickly and as in a different way than other viruses that basically appeared here in China, but they remain here in China, COVID-19, SARS-CoV-2 basically spread out throughout the world in this kind of picture that I am presenting here. And unfortunately, this picture probably has bigger red dots than the ones that I am presenting here. If we look just bringing as a matter of example, a kind of numbers of patients being diagnosed per day in Spain since, let's say, mid-March, that was basically the official lockdown for the first wave. And unfortunately, although we were quite good in stopping the virus transmission after the first wave with really very strong lockdown measures from July last year, basically one wave has been mounting on top of the other one and we are around what we consider the fourth wave. And of course, these waves have been associated with a significant number of people dying from this viral infection, something that probably none of us would have thought that this was going to happen to us, I mean, before December 2019, at least myself. So what's the clinical impact of SARS-CoV-2 in hematological malignancies? So the epidemiology of this respiratory virus infection in oncohematological patients is somewhat in parallel to that of the general population. And I'm just going to show you an example of that. But we have to take into consideration that the clinical behavior is completely different in immunosuppressed patients. So the clinical picture is more severe. We have already seen that the viral expression is much more prolonged in immunosuppressed patients. There is a more frequent transition and I have already shown you maybe quite too quickly some prognostic factors to move from an upper respiratory tract infection to a lower respiratory tract infection. And we have a higher mortality rate in this situation. This is what I was telling you before about this quite similar epidemiology between what has happened in the general population and what has happened in our hematological patients. And this figure here on the right-hand side has been taken from one of these official information coming from the Ministry of Health in Spain. So starting here on the first in March in 2020, that basically represents the new cases diagnosed by PCR during the first wave. And here you can see which was the number of newly diagnosed COVID-19 infected patients in a retrospective analysis that we did basically looking at the infection of hematological patients during the first wave. So from the beginning of March to basically the end of May. And that's let's say the title of this paper. And here we try to analyze the risk factors and the outcome of COVID-19 infection in patients with hematological malignancies. And we put in a special emphasis in looking at those patients that had been transplanted either autologous or allogeneic stem cell transplantation. And we identified, first of all, some risk factors for these patients to develop severe pneumonia. The first one was hypertension. That's very important to remember because sometimes the risk factors for morbidity and for mortality related to SARS-CoV-2 infection is not exactly related to the underlying disease but it's related to the comorbidities that the patient in this case has in addition to the underlying disease. So hypertension was able to increase in this analysis twice the incidence of severe pneumonia. Also we have to take into consideration infopenia. And also we have to take into consideration inflammation parameters like CRP. Another important thing is that we were able to identify some risk factors that were associated to mortality related to COVID-19 infection. And I want to highlight age, which maybe it's not a surprise for anybody. Those patients that had active disease at the time of infection also had a higher mortality rate. Notropenia was also an adverse prognostic factor, as I have mentioned, for the development of pneumonia inflammation. And basically we are using CRP as a marker for inflammation. And last but not least, the performance status of the patient that had also a significant impact in mortality. So another example, because I have to say that initially we didn't have any information about it, but I mean the scientific community and all the allied partners were so quick in producing information regarding the impact of this infection. In this case, hematological malignancies that the literature was completely overloaded with different manuscripts. And here you have another analysis that was published by the Italian group also looking at the clinical characteristics and risk factors associated to COVID-19 severity in patients with hematological malignancies. And what they found is something quite similar to what we found in our retrospective analysis. So age was an important prognostic factor. And there were some specific hematological malignancies, acute leukemias, lymphoproliferative disorders, and I would include here class muscle myoplasm as a lymphoid malignancy that were adverse prognostic factors in terms of mortality due to this infection. And finally, at the end of last year, December 2020, we had the information coming from a systematic review and meta-analysis in more than 3,000 patients that had been included in prior retrospective analysis. And here you have the take home messages. So the mortality appears to be high in patients with hematological malignancies and COVID-19 infection. There were some prognostic factors that were quite constant in the different manuscripts, in the different analyses that were published. So basically age, all the patients older than 60 years had a higher mortality related to the infections, also non-white patients. Having received recent systemic anti-cancer therapy was also in some cases associated to an impact in the mortality, but of course there was also a higher proportion of patients that were able to survive. And in this slide, you can see what I have already said in a kind of a graphical way. So adult patients, as usually happened, do less well than children. Here you can see the impact of age, also the not so clear impact of recent anti-cancer treatment, although there are some manuscripts or some analysis that indicate that recent treatment has a negative impact in terms of morbidity and mortality, and also the impact of race non-white patients doing worse than white patients. So we have had a look, let's say, an overall look at the clinical impact of SARS-CoV-2 in patients with hematological malignancies. What about the clinical impact in patients with multiple myeloma? And here, as a matter of example, I'm bringing a paper that the Spanish multiple myeloma group, the Gempe Temma group, and this paper was co-authored by Joaquín Martínez López and Mary B. Mateos. So we were looking at the clinical characteristics and prognostic factors for those patients with multiple myeloma that were admitted in a big number of Spanish hospitals in hospital because of COVID-19 infection. And we also wanted to compare the outcome of these patients with the outcome of a population, of a general population of patients, so patients with non-hematological malignancies that had been admitted at the same time in the same hospitals where these multiple myeloma patients were admitted. And to make this story short, we basically included almost 200 patients reported from 73 hospitals and just to show you that this analysis came from the patients that were admitted during the first wave, so March and April in Spain 2020. And this analysis is ongoing. So the, I mean, one piece of information which is important is that the inpatient mortality was higher in patients with multiple myeloma than in patients with non-cancer, 34 percent and 23 percent. Among multiple myeloma patients, the inpatient mortality was 41 percent in male. It was higher in the elderly population of patients, older than 65. It was also higher in patients with active and progressive disease at the time of being admitted. And also renal disease was a negative prognostic factor in terms of mortality and morbidity. And all these factors were independent prognostic factors when we did these multivariate analyses. And here you can see, I mean, the same information I have given you in a graph, in a more graphical way. So age older than 65 was an adverse prognostic factor, the presence of renal, renal disease, also patient with active disease or progressive disease at the time of being infected, some specific multiple myeloma features at the time of diagnosis and treatment. And prior stem cell transplantation did not have an adverse prognostic impact in the series. So of course, I mean, just focalizing our attention in patients with multiple myeloma, it's clear that these patients with multiple myeloma represent a vulnerable population of patients that was clearly recognized. And here, as an example of the multiple efforts that have been done over the last few months to establish an adequate management of patients with multiple myeloma during this COVID-19 pandemic, I'm putting here this consensus paper coming from the European multiple myeloma network with many very famous names that probably you will be able to recognize. And to finish this part of this, of the presentation, just a summary of some mortality rates looking from different, let's say, countries or eventually areas, looking at different types of hematological malignancies. And we have to recognize that, let's say, mortality rates in some cases are above 30%, or eventually 40%, and this has to be taken into consideration. So when we try to think, because I mean, we have already seen that for those patients being infected, and basically for those patients that had to be admitted in the hospital, because this is one thing that we are probably analyzing now, and we have not analyzed so much, or we did not analyze so much at the very beginning, because all these studies were basically focused on those patients that had to be admitted because of COVID-19 infection. But of course, we were missing, and this is one thing that it's being analyzed nowadays. We were missing those patients that had COVID-19 infection and did not have to be admitted in the hospital. But for those patients that had to be admitted in the hospital, we have seen that the infection is really severe. We have been able to identify some prognostic factors. We know some figures in terms of mortality. But then what happens when patients are being infected with COVID-19? And that's the other thing that we need to take into consideration, because these considerations about seroconversion will take me to discuss with you some question marks that we still have nowadays regarding the vaccination plan. So what we know about seroconversion, so which is the capacity and that's very important for patients that are immunosuppressed to mount an immunological response, either a humoral response or a cellular response when patients go through a severe COVID-19. So what you can see here in this paper that was really very recently published only a few weeks or months ago, or very in 2021, is that in general the capacity of patients with the underlying diagnosis of cancer, the prevalence of IgG after having gone through COVID-19 infection is significantly lower than in those patients that went through COVID-19 infection, but did not have the underlying diagnosis of cancer. And this is one thing that we have to take into consideration. And I'm bringing here some examples that are basically looking at hematological patients, indicating the somewhat low capacity of hematological patients to mount a humoral and eventual cellular response to COVID-19 infection. So in this study that included a small number of patients that were infected by SARS-CoV-2, only two out of 12 patients were able to generate IgG antibodies. So that's an example of the capacity of patients with hematological malignancies to develop IgG antibodies against the infection. And this is one thing that we will have to take into consideration when talking about vaccinations and vaccines in this specific population of patients. And here I have brought some really very quick examples that have been taken from very recent publications that have appeared in the literature. So in these analyses from CLL patients, the percentage of patients that were able to develop IgG antibodies in front of SARS-CoV-2 were 67% in this study looking at the small numbers of transplant patients and patients being treated with CAR-T cells. The percentage was 60% and in AML, in this really very small group of patients, 88%. And in this study, which was a prospective study that was published in January this year in the Annals of Oncology, the authors were basically looking at the seroconversion capacity of patients with cancer, basically solid tumors in relation to healthcare workers in an oncology unit. So in this specific case, the data showed that there was no clear difference between the capacity to detect IgG antibodies against SARS-CoV-2 between cancer patients and healthy subjects. But this is one thing that we have to take into consideration when let's say looking at the capacity to respond from an immunological point of view to the infection first and potentially to the vaccination later on. So let's go back a little bit, not talk about COVID-19 and just think about vaccination in hematology, which is our prior experience. I mean, I'm sure that all of you are aware that many hematological patients have a vaccination calendar and this is one thing that we are doing every single year and that for transplant patients we have a very clear vaccination program to try to give the patients all the immunity that has been lost because of the transplantation procedure. And here I'm bringing this example that it's being discussed almost by everybody right now about the role of RETOXIMAP to allow an immune response to vaccination in lymphoma. And the summary of this slide is that the use of monoclonal antibodies and the CD20 in this specific case and here data basically come from the information we have from flu vaccination is that it's quite difficult to mount an immune response for those patients that are under RETOXIMAP treatment or have just finished RETOXIMAP therapy. So that's one thing that we need to take into consideration. If we look at patients with chronic lymphocytic leukemia, so it's also quite clear and this information comes from the flu vaccination is that the response of these patients to this specific vaccine was not so good enough with quite a lot of responses coming from different studies that have already been published and even this is not only the case with RENTOLYChemotherapy but also there is a low response rate to flu vaccination in patients that are being treated with ebrutinib that you may know it's really a quite extended and almost universally used, let's put it this way, bitcaying inhibitors in patients with CLM. And we have identified and this is not the setting still for SARS-CoV-2 but there are some prognostic factors that can eventually impact the immune response of the patient to vaccination. If we talk for instance about transplant the shorter time interval between transplantation and vaccination, low lymphocyte counts, low immunoglobulin levels, the presence of active graft versus host disease, the active immunosuppressor therapy and eventually RETOXIMAP therapy over the last 12 months. So that's one thing to be taken into consideration but of course it's very clear that what we want to achieve with vaccination in general not only immunosuppress patients but also in immunocompetent people is this what we call the group of immunity to try to stop the infectious capacity of the virus as much as possible as it's more or less depicted in this graph that I am showing here in this slide. So taking all these things into consideration which has been the vaccination planning in Hong Kong hematological patients and I'm going of course to give a special mention to multiple myeloma patients. So first of all I think that everybody's aware that the development of vaccines against SARS-CoV-2 has gone through a quite not different but a more speedy process than the traditional development of vaccines in a situation outside the one that we are living and here you can see that the normal process which is presented here in the upper side of this slide with preclinical studies, development of preclinical and toxicity studies and then clinical trials starting with phase 1, phase 2 and phase 3 and then submitting all this information to the regulatory agencies FDA, EMA and then start with the large scale production which can take quite a long time several years. It has been really speed up when we talk about SARS-CoV-2 vaccine development basically because many of these phases have been mounting one on top of each other to try to accelerate as much as possible this process and try to reach this kind of group immunity that we were discussing before. So these are the vaccines that we have nowadays. So basically I want to mention these messenger RNA vaccines so the Pfizer BioNTech which was the one the first one that we had in the market and then the Moderna vaccine you know that we have two different shots here and basically separated by three weeks then we have the non-replicating vector vaccines that are basically using adenoviruses and here I want to mention the AstraZeneca vaccine and then the Johnson vaccine that basically is the last one that has been approved and it's being distributed by different European countries and here the responses to the vaccines against SARS-CoV-2. So with higher rates with Pfizer and Moderna and with somewhat lower rates but of course we need to understand that the development of the different vaccines is not exactly the same so maybe with the other types of vaccines. So I mean I'm just bringing and I have to apologize because these slides are in Spanish just I want to give you as a matter of example how the process of vaccination has happened in Spain and I imagine that it has been quite similar in different European countries of course always taking into consideration the specific aspects that apply to the different countries. So here you have let's say a kind of advertising that was published in the official web page of the Spanish Society for Hematology and Hemotherapy basically indicating the pressure that the scientific societies have put in the healthcare system and the Ministry of Health to try taking into consideration the high morbidity and mortality that COVID-19 infection has in hematological patients to try to put a pressure to try to include this specific group of patients in the vaccination programs that are in Spain and I guess that this has been quite similar in other countries was basically related to the age of the patient. There were and there was a manuscript that was basically collecting all the recommendations coming from the Spanish Society of Hematology of Vaccination COVID-19 vaccination in a hematological patient and that was really a big document that was under the umbrella of the Spanish Society but had the input and the participation of the different working groups and then we ended up with let's say a press note that was published on the 11th of March this year indicating that transplant patients, solid organ transplants and oncohematological patients were candidates to be to receive vaccination or to be vaccinated in a priority way. When talking about vaccination we have to take into consideration several aspects and probably some of the questions that we'll be coming later on will be touching these different aspects. First of all we have to take into consideration that hematological malignancies are diverse and are not exactly the same. We have to take into consideration the absence of scientific evidence regarding the efficacy of vaccine in patients with hematological malignancies because as you know these patients were actively excluded from the pivotal perspective clinical trial as usually happens and we have some available scientific evidence regarding all the vaccines that we have been using for many many years in this population of patients. So when do we have to vaccinate against COVID-19 and which are the general recommendations this slide is quite busy and for the sake of time because we want to focus our attention in multiple myeloma patients I'm just going to go to this slide that tries to give some recommendations on what to do with patients with multiple myeloma and other plasma cell disorders and taking into consideration I hope you can see while this slide that the mortality of COVID-19 infection was higher in these patients in multiple myeloma patients that we have seen than in the general population of patients and the other thing that we have to take into consideration is the poor response that we have seen in several analyses when talking about influenza vaccines. So we have to take into consideration those patients that are severely neutropinic. The recommendation is to vaccinate every single patient even patients with smothering multiple myeloma and other less aggressive let's put it this way monoclonal gamopathy. So if the patient has active disease we try to our recommendation is to vaccinate the patient without stopping the active treatment but basically between cycles some days before the beginning of the next cycle if the patient has the multiple myeloma and the control we can eventually consider to hold the treatment between seven days before and seven days after vaccination there are some indications to eventually stop glucocorticoids during vaccination and to avoid high dose immunoglobulins at least one month prior to vaccination but nevertheless I think that it's very important to take into consideration that we don't have clear evidence in the literature that what we are doing is the 100 correct thing so we are basically extrapolating some of the recommendations from other settings and I basically want to finish my presentation with let's say some information regarding the efficacy of COVID-19 vaccine in our patients so this is one thing that we really don't know when we talk about vaccination and all the discussions on which are the patients that we need to vaccinate when these patients need to be vaccinated the most important thing are not the adverse events that we can assume that are associated with vaccination but basically what we really don't know is the efficacy of COVID-19 vaccine in patients with hematological malignancies and I have brought here two very quick examples that have with two papers that have just been published I mean one of them it's almost still not impressed I mean it's impressed but they are really really very new this paper analyzes the efficacy of Pfizer vaccine in patients with CLL and I have just highlighted here things that I wanted to mention you and basically I mean these 52 patients were compared with 52 sex and age much healthy controls so we have to take into consideration something that we might eventually guess with information that we already had that the response rate was significantly reduced in CLL patients with respect to healthy control that the response rate was highest in those patients that achieved the clinical remission after treatment followed by treatment naive and it was quite low in those patients that were under treatment at the time of vaccination that also those patients that were treated with btk inhibitors or penetraplugs plus minus anti-city 20 antibodies the response rate were quite low so that's one thing to be taken into consideration and a similar information can be taken from this very recently published paper that was published online only in April 19 that was looking at the response to first vaccination in patients with multiple myeloma so these are things that we need to take into consideration and unfortunately we don't have answers to these questions so we still need to learn which is the best way to vaccinate patients with oncochematological malignancies because we can eventually assume that the umumeral response and the cellular response is not going to be as good as in the healthy population of people and that we eventually will need to change the schedule of vaccination just according to the response rate that we get and here I wanted just to highlight some limitations to vaccination that are related maybe to daily problems how is the vaccine being distributed centralized versus decentralized administration of vaccines in some areas we lack a comprehensive list of patients with hematological malignancies and this does not make our task really very easy so these are the future challenges that I have already expressed just a little bit before the access to vaccine the security and efficacy of vaccination but basically I think that security is an issue but probably the most important question marks are on efficacy the probability to circumvert after vaccination the cellular response to vaccination and I think that this is my last slide which basically summarizes what I wanted to share with you something which is very clear nowadays but maybe six months ago or nine months ago was not so clear so the vulnerability of patients with hematological malignancies to SARS-CoV-2 infection that we have been able to identify some prognostic factors which are quite constant in the different analysis and that have already been presented hematological malignancies are quite very heterogeneous and because of what I have seen patients with hematological malignancies have been prioritized in the vaccination programs and we really need to learn more about it because maybe responses are going to be lower than in the general population of patients and maybe and we should be we should work in the future in select a better vaccine and the best time point for vaccination so thank you very much for your attention and now I'm happy to take some questions and comments so I'm going to stop sharing the presentation. Thank you very much doctor for this wonderful presentation we already have some questions but before going and respond them I would like to remind people in the webinar that they have two ways to ask questions one of them is in writing in the question and answer window and the other one is just clicking the right hand button so I will I will mute you and you can ask the question directly to the doctor. One of the questions that we received in fact so many times is about those articles in the Lancet and blood I know you mentioned that in your in your presentation as well but they show that the vaccine might be less effective in myeloma patients what are your thoughts about that and and also even if the vaccine is less effective I guess there is very important to get vaccinated anyway for patients. Yeah so let's say I think that I would like to make some remarks on that I think it's very important to get vaccinated no doubt about it and I think that this is being demonstrated on how I would say that at least in the European map all the governments have tried to prioritize as much as possible vaccination in multiple myeloma patients and in oncohematological patients in general after having said that I think it's true and probably either although we don't have a lot of information already published in the literature because as you have seen these two papers that I have briefly presented are really very new probably and this is also my guess although I don't have a personal experience on that the capacity of multiple myeloma patients in this specific case to respond to vaccines is not going to be the same than the healthy population of people and maybe the response rate is going to differ between different subgroups of multiple myeloma patients. We need to know more about it and I think and this is what we are doing in Spain so there is a proposal in which many hospitals will try to participate to analyze in depth the response to vaccination both the humoral response in terms of antibody, IgG antibody producing and the diesel response of hematological patients to vaccines in the way that we are vaccinating now our patients so we are following the label so two doses for Pfizer for Moderna which are the basically the vaccines that are being used at least in Spain and I think that in other countries basically for patients with hematological malignancies so we need to study that we need to understand which is the response and which patients within a specific disease group are going to respond better or worse and when we know that and I think that this is going to be done in parallel because the science is moving so fast in this field then probably all these studies are going to be moving in parallel we will need to understand if the way that vaccines are being used nowadays is the best way for our patients. This seems to be at least for the time being the best way for healthy people and these are the population of people that have been studied but we don't know about these specific populations so but independently on that I think that the message is that everybody or all of you need to get vaccinated. Thank you doctor and relation with what you just said about the vaccines and the different vaccines that we have there are some questions about what is the difference between them between all the vaccines and what vaccines is more recommended to patients one of the questions says that for example in in the Netherlands they are using Moderna for patients but that person asked if it's the same in all countries and then what is the difference between. Okay so basically basically the recommendation is to use this messenger RNA vaccines because when talking about immunosuppressed patients we can always think that vaccination can eventually produce the disease itself and of course this is one thing that we don't want so in principle I would say that Pfizer and Moderna are the ones that are being used there are differences between them but from a practical point of view that does not seem the case and I have to say that we are using Moderna in our institution to to vaccinate all our hematological patients and I think that probably there are some issues related to the supplies that may change that or eventually policies but I would say that probably there is no difference between Pfizer and Moderna at least that I know of but we are still starting with the whole process. Thank you doctor and one of the questions that we are receiving now is can myeloma patient be vaccinated with Pfizer with a 42-day interval between those one and those two? Well this is one thing that has been let's say publicized a lot and in principle that was not I mean that was not the time interval that was in the label but there are some studies indicating that the rate of immunity does not change after having said that I go back to the information that we have and the information that we have basically relates to healthy people so it's always a question mark on which will be the impact even using 21 days for patients with multiple myeloma in this case. I'm sure Sorriana I'm sure that that many countries or all the most of the European countries are conducting nowadays and I'm sure and I know that many studies trying to follow really very closely the response rate of patients to vaccination and probably and this is what always happens in science unfortunately that at this specific time point we really don't know exactly 100% the truth and if we are going to discuss the same issue maybe in one year some of the questions that all of us have will have completely been solved by all the investigation that it's being done nowadays. Thank you doctor the next question I am a myeloma patient on third light of treatment of with chemotherapy based on linalidomide, exasamide and dexamethasone how does this chemotherapy that affect my immunity to COVID? Well let's say we have already seen that at least in some studies active disease and active treatment it's let's say a risk factor let's put it this way for developing COVID-19 infection so probably even within multiple myeloma patients it's not the same thing to have the disease information and not being under any specific treatment that being with active disease I assume and that's the reason why I mean you are in a specific under active therapy so that's one thing to be taken into consideration we always have to think that and the let's say the infectious risk it's not only because of the line of treatment that you are receiving right now but eventually also because of the prior history of prior treatments of a longer standing disease so that's another thing that has to be taken into consideration so at the end of the day the prior treatment history of the patient has an impact if in many aspects and probably will have also an impact in the risk of getting the infection so I would say that in this specific situation it's clearly indicating indicated the vaccination with all the question marks that we have discussed before thank you doctor and I just also some clarification of one of your previous responses you mentioned that for patients usually it's recommended Pfizer and Moderna and and some people have some questions about if you only can access to the AstraZeneca vaccines or Janssen and you should get vaccinated anyway so do you have to wait until you have any other available no I think that it's as always in this life is a question of balancing risk and benefits cons and pros I think that the message is that vaccination will be the only way to stop COVID-19 pandemic with what it represents and that all the vaccines have demonstrated efficacy so if Pfizer or Moderna is not available AstraZeneca or Janssen have been approved by all the regulatory agencies FDA and EMA and they can do the job thank you doctor and one of the questions related to this topic as well I have been vaccinated once with AstraZeneca can I ask for the second vaccination with Pfizer or Moderna I'm not so sure how how to how to answer this specific question I would say and that I would probably continue with AstraZeneca I don't have clear ideas if let's say switching to a different one makes a lot of sense yeah and I guess that will depend also on the guidelines of each country and how they decide absolutely this is one thing that I mean I have tried to mention during my presentation and of course because I am Spanish I have focused my attention basically in what we are doing in Spain unfortunately it's a moving field so probably if you review different guidelines the guidelines are not going to say 100% the same and probably the guidelines are going to change over time and of course I'm sure that there are different regulations in different countries that will make things a little bit different thank you doctor next question I'm a 70 for chemotherapy and a little might dexamethasone as a third line of treatment I have had to vaccination and have antibodies how is my risk level well you are not 100% free but having antibodies if they last long enough let's say I think that you are in less risk than many of other people so let's say we are being vaccinated and we are being told we still have to take care and to continue with the same let's say distancing measures that we have been taken for the last one year and a half so but of course at least for the time being you have antibodies which does not prevent 100% to be infected but it prevents a lot and that the same person asked my vaccine was AstraZeneca good third vaccination help we don't know thank you doctor one of that well the next question what is the efficacy on the vaccines on different strains do the vaccines cover all of them or only some of them so I think that the level of information that we have is not exactly the same with the different vaccines so it's and probably I mean for the vaccines that have been more news in the market more or newer in the market so for instance AstraZeneca and Janssen there is I mean there is quite a lot of scientific work to try to overcome these issues so for instance AstraZeneca seems to be less effective with the South African variant for those mild and moderate let's say uh infect infective cases and it it's a it seems to be efficacious or efficacious for the britannic variant but they are doing quite a lot of studies uh first Pfizer seems to be effective for the UK and for the South African variant and it seems that for Moderna although the at the end the level of antibodies does not seem to make a difference but it's the effectiveness seems to be somewhat reduced with the South African variant but I would say that this is quite the preliminary information depending on the let's say the the the sources that you read maybe the information is different but um and probably we will be having additional information but that's basically the information I have and of course probably the ones that appeared first and with and with what we have more experience probably have let's say a more solid data regarding specific variants thank you doctor I know we are over time and I would like to ask you as the last question and probably the rest of the question that we have maybe they can send them by by email we have the questions here so maybe we can send them to you by email so I would be happy to answer all the questions that we have not been able to answer now so the last question uh do you have any recommendation for smoldering myeloma patients even though we are not in treatment with chemo I would like to know if there is any special attention when receiving the vaccination I mean I would say and this is one thing that we are doing we are we are vaccinating patients with a smoldering myeloma it's true that maybe I mean the risk of COVID-19 infection is not going to be exactly the same because the disease in inverted commas is not active you have not received prior therapy just because of the disease but but the recommendations is that uh that you and let's say the rest of the people in this situation get vaccinated thank you doctor and and the last question and now for real is I am a myeloma patient and I'm doing I'm going to be treated tomorrow with the ratumumaf prevision and dexamethasond and I start at year of 21 uh day with Lena Lidomite I had my first dose on Pfizer on uh 26 on April what should I ask so to get I mean if the first dose is already in then you have this you have to have I mean you have to get the second dose um in patients with active treatment let's say the recommendation but let's say the level of evidence is what we have right now is to try to vaccinate uh in the week before let's say in this case because Lena Lidomite it's Lena Lidomite Dara and Lena Lidomite or Dara and dexamethasond Dara and Lena Lidomite and yeah I think Dara and Lena Lidomite okay so Lena Lidomite will be most of it continuous but with Dara tumumaf so probably I would give uh let's say the second shot uh one week or between the last week before receiving the next dose of Dara well thank you very much doctor and uh well thank you for responding all the questions if uh we keep uh receiving questions I will send down uh by email to you so you can answer them and just remind everybody in this in this webinar that this webinar uh has been recorded and will be uploaded to the myeloma patient Europe website uh which is www.wmpyoutube.org and it will be available also in our youtube channel so thank you very much for your time doctor and uh thank you all for for joining us today and have a nice evening thank you thank you very much for the invitation thank you Anna thank you