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May 22, 2020

Dr. David Fajgenbaum is the author of the bestselling memoir, Chasing My Cure: A Doctor’s Race To Turn Hope into Action, and this year’s Guest Speaker during the ASCO20 Virtual Scientific Program Opening Session. In this episode, Dr. Fajgenbaum shares his extraordinary story of survival and the quest to find a cure for the rare Castleman disease from which he nearly died five times. He also tells us how he is adapting the methodology he used to search for a treatment for his own condition in the quest for a therapy for patients with COVID-19.



ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. I'm thrilled to welcome Dr. David Fajgenbaum, this year's guest speaker during the ASCO20 Virtual Scientific Program opening session. Dr. Fajgenbaum is the author of the best selling memoir, Chasing My Cure, A Doctor's Race to Turn Hope Into Action. It's an extraordinary story of survival and the quest to find a cure for the rare Castleman disease from which Dr. Fajgenbaum nearly died five times.


Dr. Fajgenbaum leads the Castleman Disease Collaborative Network and the Center for Study and Treatment of Lymphadenopathies and Cytokine Storms at the University of Pennsylvania's Perelman School of Medicine. He is also assistant professor of medicine in translational medicine and human genetics, and associate director of patient impact for the Penn Orphan Disease Center. Dr. Fajgenbaum will discuss how he is adapting the methodology he used to search for a treatment for his own condition in the quest for therapy for patients with COVID-19.


My guest today reports no conflicts of interest relevant to this podcast. Full disclosures relating to all Daily News podcasts can be found on our episode pages. Dr. Fajgenbaum, welcome to the ASCO Daily News podcast.


Dr. Fajgenbaum: Thanks so much for having me, Geraldine.


ASCO Daily News: Congratulations on your wonderful memoir. Tell us about your experience with Castleman disease.


Dr. Fajgenbaum: Sure. So I went from being a healthy third-year medical student, training to become an oncologist in memory of my mom who had passed away just a few years before from a glioblastoma to experiencing multi-organ failure. I was just so, so, so sick. I felt more and more fatigued, and then the fatigue turned into night sweats, and I noticed enlarged lymph nodes.


And soon I went from one of my medical school rotations down the hall to the emergency department, where they ran a series of blood tests. And blood tests came back suggesting that I had liver, kidney, and bone marrow dysfunction. A CT scan revealed disseminated lymphadenopathy, and all of us thought the worst. We thought that I had a high-grade malignant lymphoma.


Unfortunately, I became really, really sick over the next couple days. I was transferred to the intensive care unit. I had a retinal hemorrhage that made me blind in my left eye. I drifted in and out of consciousness. And no one thought I would survive.


For the next 11 weeks, I existed in this state of multi-organ failure, a true cytokine storm in its purest sense, where I had a C-reactive protein level through the roof and my organs were failing. Eventually, after 11 weeks, I was eventually diagnosed with Idiopathic Multicentric Castleman disease, a cytokine storm disorder where there's immune hyperactivation and that leads to multi-organ dysfunction.


Thankfully, I got the diagnosis really just in time because I was so sick that the doctors told my family to say their goodbyes, and a priest came in to administer my last rites to me. But thankfully, with the diagnosis, I was able to begin treatment. Unfortunately, I would go on to have many, many more relapses.


ASCO Daily News: You have this rare disease for which there was no known therapy. What can other physicians who are in a similar situation with COVID-19 take from your experience searching for a treatment?


Dr. Fajgenbaum: Sure. So when I was finally diagnosed, and finally got chemotherapy that saved my life, I was put on the first experimental drug, the first drug to ever undergo a randomized controlled trial for my disease. And I remember being so hopeful that this was going to be the drug for me. And thankfully, this drug helps about one-third to one-half of patients, but unfortunately, it didn't help me, and I relapsed and nearly died for a fourth time on that drug.


And that's when I realized that if I was going to hope for a treatment and hope for a cure that I would need to turn my hope into action. And I would need to dedicate my life to trying to identify a treatment for a disease-- my disease-- which didn't have any other options. So this sense of having a cytokine storm disorder with no drugs that are working, unfortunately, is, as you alluded to, a position that I've been in before with my own disease.


And I think that there are a number of really systematic steps that we can all take, that we can both learn from my journey chasing my cure, but also for so many other amazing organizations that have made real progress against diseases with few options. I think that at the core, in order to go from poorly understood disease with no drugs to a well-understood disease with many treatment options, I think that there are a few fundamental pieces.


So first, I think it's critical that physicians, researchers, patients, and industry work together. There is just no way that any one of those groups can do this on their own. It's critical that people come together to collaborate. Next, once you get everyone together-- and so it might be physically through in-person meetings, but it also could be virtually through online discussion boards.


Once you convene the stakeholders, in my opinion, I think the next step has to be a crowdsourcing effort where you start getting research ideas, research questions, priorities, from the whole community. Don't just raise money and hope that the right researcher applies for the right project at the right time. Let's get everyone proposing ideas. No idea should be off the table. And I think here with COVID-19, I think we all agree that no ideas should be taken off the table.


So build the community, generate as many possible ideas as you can from all stakeholders for what research you can do, what drugs you should consider. And then go through a really systematic approach of prioritizing what is the most important study to do. Then go out and recruit the best researchers for those given studies that you've prioritized to actually do your work. And in parallel, engage patients to actually be able to contribute their samples and their data directly to this centralized research approach.


And as you get data back, go through the incredible databases that exist of already FDA-approved drugs. And ask the question, based on what I've found in the research, are there any drugs that are already approved that might actually be able to treat this disease? This kind of eight-step approach that I just went through briefly, this is what we call the collaborative network approach.


It's what we've pioneered in the fight against Castleman disease. It's what has led us to where we are right now. And it's what I really detail in pretty extensive detail in my book, Chasing My Cure, because I wanted to be able to share our approach, our experiences, not because they're necessarily the right way to do it, but because they're a way that it's been done where there have been some really promising progress from. And I'm literally alive today, talking to you, because of a drug that came out of that collaborative network approach process, and because of a drug that we repurposed that no one would have ever thought to try if not for this systematic approach.


And so I think each of those steps need to be considered when we think about COVID-19. Obviously, there is a sense of urgency to COVID-19 that many of us, especially in the rare disease space, always have for our given rare diseases. But we really need to make sure we move as quickly as we can.


ASCO Daily News: Well, in your case, the sharing of information played a crucial role in finding a drug that could help you. And you've just described how this approach will help in the search for a COVID treatment. Tell us about what you're doing now with the COVID-19 Registry of Off-label and New Agents.


Dr. Fajgenbaum: I found myself about-- I guess it's six or seven weeks ago really upset, like so many listeners, I'm sure, also feel about the fact that this pandemic is wreaking so much havoc, not just in our country, but in the world. And I remember, I was driving in my car-- and this is really before everything is shut down-- and I was thinking to myself, I really hope that some research group out there will follow this sort of approach to drug repurposing, where you go through existing data, you perform additional analyses, you look for potential targets the drugs can be used against.


And then when drugs are used off-label, you really systematically track what drugs are being given, how frequently are they being given, what are some indicators they might be working or not working? There really has to be an entire pathway, if we think about drug repurposing, from discovery around what could work, through in vitro testing what may work, all the way to when you've given it to humans, make sure that you're really tracking what has been given and what is working in humans.


And of course, the best way to do that is through a randomized controlled trial. Unfortunately, with the kind of pace that things are moving at, there are a lot of nonrandomized control trial data that have been generated and exist. And so we felt-- and I mentioned this is about seven or eight weeks ago-- so I knew drugs were going to be used off-label against this disease, and they already it started to be used off-label.


And I really felt that we needed to take an approach to centralize all of those data in one place. And so I turned to my research lab-- now I work UPenn, where I run a lab and a center focused on studying Castleman disease and other cytokine storm disorders, and decided to redirect my lab and the foundation I run to focusing on COVID-19. These are both Cytokine storm disorders, they're both diseases that are quite poorly understood, and that are most likely to benefit from repurposing in the short term.


I hope that new drugs get developed that are the perfect treatments for COVID-19. But in the meantime, the best we can do is to identify existing drugs. And so kind of given the fact that we've done this before for Castleman disease, we study Cytokine storms, and we track systematically when drugs are used off-label and experimentally for Castleman disease, we decided to do the same thing for COVID.


And so we manage this huge database of every single drug that has been given to any patient with COVID-19. I have a team of amazing lab members and volunteers who have gone through over 4,400 published papers and pulled out data on over 11,000 COVID-19 patients, where we found approximately 150 different drugs have already been tried. Now of course, finding out that the drug's been tried against COVID-19 doesn't mean that it's going to work or that it even did work in that patient.


But it's critical, in my opinion, that if drug repurposing occurs, you need to systematically track what has been given, how frequently has it been given, and is there any sort of sense from the off-label data that can suggest that it might be working or might not work? So you can then effectively and efficiently move forward to clinical trials. So we're managing those databases, updating it. As we speak, there are dozens of people that are working on this. And we want to continue to make this resource available to any physician, researcher, governmental body that wants to understand what repurposing has been done to date.


ASCO Daily News: Has the COVID-19 pandemic caused you to reflect again on your own journey? You often speak about this feeling of living in overtime.


Dr. Fajgenbaum: Absolutely. I've nearly died five times battling a cytokine storm. And I have experienced the feeling that so many of us feel right now, of fear and of sadness. And as you said, living like I'm in overtime. And what I mean when I say I feel like I'm in overtime is that ever since I nearly died the first time, I felt like I have this extra time that is kind of like overtime.


I played college football at Georgetown, and so I know a little bit about what it's like to play in overtime games. And in overtime, because the time is limited, because you have limited time left from the clock, there is this incredible sense of clarity that comes from that, and focus on what's really important in life. And ever since I had my last rites read to me, and I felt like I'm in overtime, it's given me a real clarity about what's important.


And so though you would expect that maybe hearing a clock ticking would create fear-- and it certainly can create fear. But for me, hearing the clock ticking has created fear, but then that fear has-- I've been able to turn that into hope, into action. And so basically, to say, I'm going to use the fear to channel my energy towards doing things that I'm hoping for.


If I'm hoping that a researcher somewhere is going to figure out a drug that could maybe be repurposed against COVID-19 or track the use of drug repurposing, then I'm going to do that. I'm going to take action. I also found from being on my deathbed that the things I regretted the most of my life were not things that I did. The things I regretted were the things I didn't do or I didn't say.


And as a result I really lived with this motto of, think it, do it. If you think of doing something and it's the right thing to do, don't talk yourself out of it. These are a couple of concepts that I think are so critical during a pandemic, and so critical in what we face while we are with COVID-19. And a few others that I'd love to share with you that I'm able to go into a lot more depth about in Chasing My Cure, but that I'd love to mention today.


And one that I think will ring true to you and to others is around the importance of humor and laughter during really tough times. You would think of that when there's a global pandemic, or when you're in the ICU with multi-organ failure, that the last thing you'd want to do is laugh, but I would actually disagree with you. And surprisingly, that when you're really, really sick, sometimes the thing that you really need to do is laugh, and to laugh with the people that you love.


There's a story I want to share that I think will certainly ring true for a number of the oncologists, especially the brain tumor docs who are listening in. I mentioned earlier, my mom was diagnosed with grade IV glioblastoma when I was in college. Soon after her diagnosis-- very soon thereafter, we had plans to do a craniotomy to take the tumor out. And we were all so worried about if our mom-- if my mom would emerge from surgery, A, would she survive this really complicated surgery? And B, would she emerge as the same person that went in?


I'll never forget walking past this banner at Duke University that says, at Duke, there is hope. And I remember saying, we're in the right place, there's hope here. And I was so hopeful. And I remember hoping and praying throughout the 4 and 1/2 hour surgery. And I remember being so nervous when I went back to go see my mom.


And I was with my dad my sisters-- and I-- and we went back to see her. Just before they pulled back the curtain, I said to my sisters and dad, let's wipe away our tears. We have to be really strong for Mom. And they pull back the curtain, and my mom was there, and she had bandages wrapped around her head. And she had a bulb coming out of her skull from where the surgery was.


And from that bulb, you could see that there was fluid being drained. And it was just so concerning, how is our mom doing? And she looked at us, and she pointed up to her head, and she said Chiquita banana lady. And she made this joke to us that though she had just come out of this 4 and 1/2 hour surgery, and though her head was bandaged because of the procedure, she thought she looked like the Chiquita banana lady.


And we just burst into tears. In fact, we burst into tears and laughter. And it was, I think, such a good example of, in the midst of really tough times, being able to find something to laugh about with the people you love, are so important.


The fourth lesson that I think is particularly relevant right now is something I've mentioned a few times already, and that's turning hope into action. So many of us are hoping for progress. So many of us are taking action, but there's a real opportunity, I believe, when we hope for something, or when we pray for something, for us to say, well, can I actually do about this today?


Another takeaway that I think is important is the concept of creating silver linings. During tough times, we're often encouraged to look for silver linings. But I actually-- something I learned from my mom is that we should really be looking to create silver linings. So even when times are tough, what can I do today, what can I build today, what can I create today that will make a silver lining in the midst of this really tough time?


And then the last one is something that every oncologist will certainly appreciate it. And that is the importance of a team, and a really good team. The work that we're doing against COVID-19, obviously, there's no way that I could have read through over 4,400 papers in days, and pulled out data on thousands of patients and hundreds of-- or dozens of drugs. But it's through having a great team and setting out a clear vision, and then working towards that vision.


And I think all of these lessons that I learned from my deathbed, chasing after my own cure, I think they've always been relevant. But I think in the era of COVID-19, I think that unfortunately some of these lessons are more relevant than ever.


ASCO Daily News: Absolutely. Well, if there's one thing the world needs in this moment of COVID-19 darkness, it's a rapid lifesaving therapy for a disease we don't yet understand. And you certainly know this life and death equation better than most. Can you tell us where we can find out more information about the COVID-19 Registry of Off-label and New Agents? And the other COVID-19 work your teams are doing at the moment?


Dr. Fajgenbaum: Sure. So anyone can go to And CORONA is the acronym for-- just because it was mentioned-- COVID-19 Registry of Off-label and New Agents. So we're tracking every drug that's being given to any human with COVID-19 in the world in this central database. And really, we've made it an open source database. So anyone, whether you're a physician, a researcher, a nurse, a health care practitioner, a governmental organization, you can go to this registry, and you can see all of the drugs that have been tried.


You can see the frequency of how often they've been used, if there's any sense as to what's working and not working, we try to put that into the database. That's a really challenging thing to do outside of a clinical trial-- we put some data in. But we really want this registry to be a starting point so that doctors and researchers know what's being given. And then we use this data and these data to then determine what drugs really need to go on to randomized controlled trials and to be evaluated the way that they need to be evaluated.


ASCO Daily News: Excellent. And we can find your book, Chasing My Cure, A Doctor's Race to Turn Hope Into Action anywhere books are sold online, and you've also done an audiobook, right?


Dr. Fajgenbaum: That's right. I wasn't sure that I wanted to do an audiobook because it's quite a commitment. It was a few days worth of work. But where I couldn't do my Castleman's research or my cytokine research. But I've got a daughter who's 20 months old, and having a disease like I had, and knowing the uncertainty of the future, I really love the idea that I could share my story in my words, and that those will always be there for Amelia.


I mentioned earlier, I've been in remission for over six years on this drug, sirolimus, that had never been used before for my disease. But I never round up. I never say it's been almost 6 and 1/2 years. It's been over six years.


But I don't know how long this remission will last for. And as a result, I really do try to live like I'm in overtime. And that decision to do the audiobook was very much in line with that. And would just be delighted for others to be able to get the chance-- whether it's listen or read-- about some of these really important lessons that I think are so, so helpful and relevant today.


ASCO Daily News: Well, I really, really loved your book. It was fascinating. So many lessons to learn for all of us. Dr. Fajgenbaum, is there anything else you'd like to share in the podcast today?


Dr. Fajgenbaum: Yes. Before we close, I just want to take a moment to thank all of the amazing oncologists out there, whether you're listening or out in the world taking care of COVID-19 patients and your cancer patients that need you almost now more than ever. And the fact that you guys are just being so brave, on the front lines, taking care of patients, both with and without COVID-19, really hard to put into words just how grateful I am for all of you, and all that you do day in and day out. I'll keep doing what I can from a research perspective, and I'll continue to be so grateful for everything that you guys are doing from a clinical perspective.


ASCO Daily News: Thank you, Dr. Fajgenbaum, for sharing your story with us today.


Dr. Fajgenbaum: Thanks so much for having me on and helping to spread the word about this work we're doing against COVID-19, and these lessons that I think we need to share with the world.


Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

COI Disclosure: 

Dr. David Fajgenbaum

Honoraria: Foundation Medicine

Consulting/Advisory: SOBI

Research Funding: EUSA Pharma, Janssen

Other: Pfizer