Christian Chabannon:

Good morning to all of you. Thank you for having Professor Anna Sureda and myself for this interview, a few days after the end of the 48th EBMT Annual Meeting. My name is Christian Chabannon. I’m a hematologist usually working in Marseille in Southeastern France. I used to be one of the EBMT Working Party chairs, the Cellular Therapy and Immunobiology Working Party chair. There is a new chair, who was elected last week, Dr. Annalisa Ruggeri. Our goal today together with Professor Sureda is to discuss the extraordinary period of time EBMT went through over the last four years. Professor Sureda will tell you a bit more about our project as the EBMT new president. Maybe we can start, Anna, discussing the somewhat extraordinary external constraints that EBMT faced over the last four years.

Anna Sureda:

Thank you very much, Christian, for the introduction and thank you very much for the invitation. I think that the last four years have been really exceptional from an EBMT point of view. EBMT has been suffering basically over the last two years or two years and a half together with the rest of the world basically because of some external problems. I would say that the COVID-19 pandemic, which is probably some of the issues that we are going to discuss later on, has had a significant impact on EBMT. As you have said, it’s a little bit less than one week that we finished our last annual meeting. Unfortunately, it has been the third virtual meeting in a row basically because of COVID-19. Unfortunately, in this specific edition, this last edition also because of the war between Russia and Ukraine, and basically because of the amount of refugees that were arriving to the Czech Republic. I would say that the daily life of EBMT has significantly changed over the last two years because of COVID-19 pandemic. The annual meeting is a good example of that. As I have said, three meetings in a row being virtual. The last one had to be changed almost in the very last minute from a hybrid version, which was a new version that EBMT tried to implement because of the COVID-19 pandemic, to the virtual one. A lot of changes for EBMT.

Christian Chabannon:

Yes. Thank you. I think it’s important to stress that the EBMT staff in particular was extremely efficient in converting a hybrid model into a fully virtual model in only a few days because I think the final decision was made approximately ten days before the opening of the session. Everything went rather smoothly if we consider the very short time that the staff had to prepare for this new format. I think it affected not only, of course, the meetings, the annual meetings, and many of the small to intermediate-size educational events that EBMT runs every year for the benefit of junior and senior investigators, were also very significantly disturbed. Some of those events were cancelled. Some of those events were in a fully virtual mode. Very few actually included face-to-face meetings. But that also obviously affected the very practice of hematopoietic cell transplant and cellular therapies. Because this is a very special medical practice where we face on a daily basis patients who are affected with very high-risk diseases or advanced diseases, and we use treatments that are entailed with very significant toxicities, I would like to hear of your opinion on how the basic training of transplant physicians prepare them to handle crisis such as the ones that you described.

Anna Sureda:

As you have said, Christian, let’s say our business, from a clinical point of view in EBMT, was significantly affected by COVID-19. EBMT had to make also an extraordinary effort on that. From a clinical point of view, transplantation being a highly specialized treatment strategy was very much affected by COVID starting with eventually the indications of stem cell transplantation or some modifications in the indications of a stem cell transplant; how to handle patients that were candidates for stem cell transplantation that were COVID-19 positive; how to deal with donors; or the problems related to the unrelated donor stem cell transplantation across barriers. Of course, if we talk specifically about training, all the usual resources that we were using for training were also significantly disrupted. Movement of trainees across borders was really very complicated. In fact, I remember of some cases of people that tried to join or to go to another country to be trained that had to go back basically because of COVID-19. All the educational activities that EBMT has been developing for trainees and for young physicians had to be also significantly modified. Let’s say in a way that you have already mentioned regarding all the different educational events that EBMT is conducting over the year. We implemented a new learning platform, I think, that probably we will be able to work on that more in the future. This is one of the objectives for the next year to try to keep the continuous education process for our young trainees and of course, for other professionals that are in training. I guess that trainees also suffered quite a lot from all the changes that were related to COVID-19 pandemic. I think that EBMT tried to overcome all these problems. In fact, I have to say that we have seen the Trainee Committee really flourishing in the last few years, a little bit coincident with COVID-19 pandemic. I think that this is a demonstration that even with all these challenges that we are facing, we can still continue to deliver adequate continuous education to the young physicians and to promote this group of really interested trainees in developing education for themselves.

Christian Chabannon:

Yes. Thank you. I think you point out to actually some benefits that were derived from dealing with this crisis. The pandemic, if we look back, actually accelerated the transition to digitalization of many educational supports and many educational needs. You were mentioning trainees. I think for them, it’s probably much cheaper and easier to access online events than it is to access traditional events. We are all joking on back to normal conditions every time we start or we conclude a teleconference. We say that we would like to see each other and share a coffee or a beer for the most adventurous of us. But I personally believe we won’t get back absolutely to what we call normal in the past. By the way, I’ve never understood exactly what is normal, but I think there will be a new normal in the future and we won’t get back to the formats that we used to know four years ago. I’d like to hear of your opinion on this aspect.

Anna Sureda:

I fully agree, Christian. Normal is a very white word. I think that everybody applies normality to his or her own life. We are talking about this new normality, which it does not seem that we have reached this point still right now, but I agree with you. First of all, that probably COVID-19 has allowed us to better understand all these digital platforms; has demonstrated that even continuous education and meetings can be done through these platforms. It’s less time-consuming. It’s cheaper, which is another important thing to take into consideration. It reaches more people because people can be connected from work, from home. There are less borders and less frontiers. It’s more compatible in many occasions with family life and personal life. I don’t think that we will ever go back to our normality before COVID-19 and that we will be taking advantage of what we have learned over these last two years, and probably use it for the best of our purposes. I fully agree. Of course, if we are talking about young people and trainees, education can be in many ways perfectly being given in a virtual format, although I still would like to see all of us face-to-face with a beer, a glass of wine, or a coffee. Hopefully, we will be able to do it, but we cannot forget what we have learned. I think that we have been able to go perfectly through this period of time, which has been really challenging, but learning things that maybe we would have learned in some years time if COVID-19 would have not been present in our lives.

Christian Chabannon:

Definitely, whenever the opportunity arise, we’ll share a coffee or whatever drink. We talked a lot about education and I think that EBMT really fulfills its members’ expectations. But at the same time, we have to run usual business. The period with the pandemic also led us to realize even further how dependent is transplant activity on international exchanges, the high proportion of allogeneic transplants that are performed from unrelated donors. We faced really weird situations, especially during the first lockdown, when trying to transfer unrelated grafts from one country to another or from one continent to another. In that view, EBMT very rapidly established a COVID-19 Task Force that is led by Rafael de la Càmara, a Spanish physician who is also the chair of the Infectious Disease Working Party, and with Per Ljungman, a Swedish physician with a long-standing member and active member of EBMT. The COVID-19 Task Force has established guidelines that are updated on a regular basis and that provides transplant physicians with guidance on many aspects of the transplant process: how to protect donors; how to protect recipients; how to best handle the graft after, during, and following transportation. Would you like to make a few comments on the COVID-19 Task Force, please?

Anna Sureda:

Yeah. Absolutely. I think that EBMT, as you have said, EBMT stepped in very quickly in the COVID-19 pandemic, and tried as the European Transplant Society to bring information in a rapidly changing field, where unfortunately the level of evidence was at some point not so clear for all of us in all the different aspects of stem cell transplantation. EBMT developed the Task Force, as you have said, it was led by Rafa de la Càmara and by Per Ljungman. There was a specific money and specific economical resources that were dedicated to this Task Force that basically had an enormous work to be done in establishing guidelines in all the different aspects of stem cell transplantation. Probably, we didn’t know before COVID-19 came in our lives how vulnerable was all the transplant procedure in this era of this viral pandemic. I think that we were learning at the same time that things were happening, but the Task Force was quick enough to give these guidelines and was able to update them on a regular basis, which is really absolutely important. Still, this is an ongoing process and work in progress able to produce scientific information that has already been presented in several meetings, that has already been published regarding the outcome of stem cell transplantations that were infected by COVID-19, looking at prognostic factors. Then of course, trying to learn more for the future. The Task Force, of course, it’s still ongoing. There are new projects coming in because, of course, COVID-19 pandemic is an evolving field. The Task Force will continue to work on that basically for the service of the scientific community, but basically for our patients.

Christian Chabannon:

Yes. Thank you. I think it’s absolutely critical that the Task Force continues its missions because it’s very important to stress that the pandemic is not over. We would all like to read and hear that the pandemic is over, but this is not the case. In many countries, the numbers of people who are infected go up again and external circumstances such as the war in Ukraine may actually contribute to the spread of the virus. We’ve heard of the situation in China. As you said, we need to protect our patients. The supply chain can be completely disturbed, especially when it involves shipping grafts of very long distances. We now know that high proportion of patients that we care for are actually very fragile when it comes to get infected with COVID. The COVID-19 Task Force, together with other professional associations and healthcare authorities, has produced recommendations on how to vaccinate recipients and donors, how to protect them using the available medications, drugs, antibodies that could help in the early phase or late phase of the disease to protect those patients. Probably most importantly, social distancing remains very important rules for donors and recipients whenever they get close to the transplant procedure. Moving to another topic, we also had to face during this extraordinary period some very important transition in our field. Of course, EBMT is a society that was created to look at the outcome of transplanted patients, survey changes in medical practices. But for four years now, the field faces a major transition with the introduction in the market of industry-manufactured gene therapies and cellular therapies. The most publicized of them are CAR Ts. EBMT has strongly committed a fraction of its resources to be a major player in the field for a number of reasons. Some of the indications for this different class of therapeutics overlap. The toxicity profiles between CAR-Ts and allogeneic transplantation is largely similar. There was a huge effort on the EBMT side to set up a continental registry, to register patients, contribute to their long-term follow-up over 15 years or longer. We had to do that at the very moment we were facing the consequences of the pandemic and everything we have already described. I’d like to have your comments and opinion in this topic and how you see the development in the future for these matters.

Anna Sureda:

As you have said, this has been another major aspect that EBMT has had to take into consideration over the last few years coincident with COVID-19 pandemic. We have had stem cell transplant as the only, let’s put it this way, cellular therapy strategy for many, many years. Nowadays, we are seeing more and more additional cellular therapy strategies, which have already come into the field. They really open new avenues for the treatment of the patients and for the long-term outcome of the patients. These are CAR-Ts. I think that EBMT, and I think that, Christian, you have been a major player in this specific area, has also undertaken this commitment with big strength from the very beginning. From a registry point of view, the implementation of the CAR-T treated patients registry, let’s say, in a similar way that EBMT has been holding the registry for stem cell transplantation patient with more than 700,000 patients being transplanted and reported to the registry. In addition to that, pharma companies or pharmaceutical industry have come really into this field. We cannot forget that stem cell transplantation as a treatment procedure itself has never been a major scope by pharmaceutical companies, but the situation of CAR-Ts has been completely different. With the EBMT efforts, together with EHA and the GoCART coalition that tries to bring together all the different partners in Europe that are involved with CAR T-cell therapy was developed some years ago. EBMT has been the major partner here together with the collaboration of EHA. Here we have, of course, the rest of the players. We have pharmaceutical companies. We have patients and patient advocates. We have HTA bodies. Every single partner that contributes to CAR-T therapy in Europe, it’s included here. The GoCART coalition has several working committees that are basically dedicated to accreditation, to patients, to scientific development of projects. This is one thing that EBMT started and we should continue working on that because, of course, this story has just started right now. The future is really open, is bright with many new products and many new advances to come. I think that EBMT will continue working on that. As a European transplant and cellular therapy society, we’ll have to play a major role once again, let’s say from a scientific point of view, with the objective to improve our patients care; from a quality and accreditation point of view, patient and advocacy groups. That will be one of the major aspects for EBMT in the next years.

Christian Chabannon:

Yes. Absolutely. Things are going very fast, as you mentioned, since the introduction and the approval of the first two CAR-Ts in Europe that was in August of 2018. Less than four years ago. We now have data that suggest potential efficacy in second-line. We’ve also heard of results of clinical research describing the use of CAR-Ts in first-line for patients with lymphoma. This is not approved yet and we obviously cannot recommend any use of CAR-T before the third-line, but we are seeing that clinical evidences are produced at a very fast pace with potential consequences in day-to-day medical practices over the next few years. The many technological developments that were highlighted both at the Annual Meeting and the European CAR T-cell Meetings that took place two months ago and maybe I would like to stress in particular, in light of the Jon van Rood award, that again, hematopoietic stem cell transplant is not dead. This is still a very active field where people are exploring ways of improving the outcome of patients receiving allogeneic cell transplantation in particular. That was the topic of the Jon van Rood award in particular, trying to dissect the different immune cell subsets that are responsible for the positive effects of allogeneic transplants, the anti-tumor effect versus the negative effects, the GvHD complications. That would be my word. The CAR-T field is moving very fast, both technically and in terms of applications, but hematopoietic cell transplant is still a very living field with many patients who still benefit from receiving either autologous or allogeneic transplantation and how our understanding of the transplant complications and outcome remain partial, and are still the topic of very active investigations.

Anna Sureda:

Let’s say it’s not a question of having CAR-T therapy fighting against transplantation or the other way around. I think it’s clear that the introduction of CAR-T is going to modify how we are using stem cell transplantation at least in some patients. Probably the best example might be lymphoma in the future, although we are already seeing some changes in the number of patients that are being treated with an allogeneic stem transplantation. Probably in the next few years, we will be seeing more and more how CAR-Ts are being positioned in other diseases apart from lymphoma. We already have information also on ALL basically in children and in the young adult setting. On the other side, we have seen that also in the meeting that we can still implement the results of allogeneic stem cell transplantation. Basically, trying to decrease relapse rate after allotransplant. We have been working for many years in MRD strategies after allogeneic stem cell transplantation, maintenance treatment strategies, and how to select… Not to select the patient, but put the patient in the best condition possible for the stem cell transplantation. One very important thing, in which Christian has already mentioned some examples, but the transplant community is working, is in trying to decrease as much as possible toxicity of allogeneic stem cell transplant. Allotransplant is the only curative strategies in many settings. But of course, this curative objective is in some cases offset by high transplant-related mortality. To better understand how to reduce transplant-related mortality and to dissect cellular subset of lymphocytes that are associated to toxicity or eventually to the beneficial effect of allogeneic stem cell transplantation is of importance. I think if I can have a look into the future that the major efforts in terms of stem cell transplantation would be to decrease relapse rate and to continue decreasing also transplant-related mortality.

Christian Chabannon:

Maybe we will conclude this discussion. I will use what you mentioned regarding the patient advocates and the Patient Committee that was recently created at EBMT that was originally led by Bregje Verhoeven from the Netherlands and the new committee chair is Natacha Bolaños, who is a Spanish patient and patient representative. I think EBMT is very much committed to listening to patients, to taking their opinions into account. What patients tell us is that this is not only the amount of life that is important, this is the way you can live all these years that you get through the administration of treatments. They are also interested in other aspects such as confidentiality. From this viewpoint, when we established a registry, we also had to deal with the implementation of the global data protection regulation in Europe. We also had to face some technical issues with the registry. Moving registries that contains data on more than 700,000 transplants and now more than 3,000 patients treated with CAR T-cell is by no way an easy task. Can you tell us a little bit on these different aspects?

Anna Sureda:

Sure. I think that you have mentioned a really very important point. I think, that there are different tasks that EBMT has already started to annotate, but that will need to be better refined in the future. The establishment of GDPR was really a big challenge for all of us being a European organization. Of course, first of all, all of us, we needed to understand exactly what it did mean because at least it took for me a little bit of time to basically understand which were the consequences of that. These had to be implemented in all the different processes of EBMT and the relationship of EBMT with the different centers. This has represented a big task that has also been done in difficult times, just going back to COVID-19 pandemic. Of course, let’s say the other aspect, which is very important to mention, is the registry. EBMT started the registry in 1974 if I am correct. We have now, as you have mentioned, a huge number of patients being transplanted and being treated with CAR-T. EBMT has been working for quite a few years right now in implementing, first of all, the platform where all these clinical data of the patients are included. Secondly, to try to upgrade the way that these data are being collected. These data are being reported by the centers to make it as easy to use by both sides. This is a task that is a work in progress and that will be a major issue for EBMT in the near future. Talking about patients and registry. Another project, with which hopefully we will be able to start in the future, is trying to include patient-reported outcomes in the registry. This is a project that has already been implemented by other registries and this is a pending issue from our side. Probably not so easy to do, but this is one thing in which we will be working. I’m sure that we will have a lot of feedback from our patient and patient advocate group, which was created several years ago. As you have said, we have a new chair, but that will be having more and more impact in the EBMT daily life.

Christian Chabannon:

Well, Anna, Professor Sureda, I think I would like to thank you for taking the time to contribute to this discussion on overview of EBMT activities, especially during again this period. I think if we summarize our discussions this morning, it’s important to stress how strong is EBMT as a professional association, how adaptive has been our community to deal with the internal and external constraints including regulatory constraints that you mentioned, as well as technicalities such as the changes in the IT systems that supports the registry, and external constraints including obviously the COVID-19 pandemic and more recently the war in Ukraine. I think it is important to stress that EBMT has already secured some resource to help Ukrainian physicians and to help Ukrainian patients whenever we can, probably playing a role as a broker between Ukrainian hospitals and other European hospitals that could be in a position to take over and treat Ukrainian patients whenever this is necessary. To conclude, I would like to thank you again and to wish you good luck for the next four years when you will be the EBMT president. We all hope that you and the team, EBMT employees and EBMT members will maintain the society at the forefront of the development of cellular therapies including cell transplants that has not disappeared as well as CAR T-cells, other immune effector cells in Europe. Thank you again.

Anna Sureda:

Thank you very much, Christian. Thank you.