A Cancer Patient’s War on Cancer

A Cancer Patient’s War on Cancer


>>Good morning, everyone. Thanks for joining us today at the NCI CBIIT Speaker Series. I’m Tony Kerlavage, the acting director of CBIIT. As a reminder to everyone, this presentation is being recorded and it’s going to be made available on the CBIIT website at cbiit.cancer.gov. You can find information about future speakers on that site and by following us on Twitter. Our Twitter handle is @nci_ncip. Today, I’m very pleased to welcome Dr. Tony Blau, who is a professor of medicine and Hematology and a physician scientist at the University of Washington. Dr. Blau co-founded the UW Institute for Stem Cell and Regenerative Medicine and chaired the Molecular and Cellular Hematology Study Section for NIH. The title of his presentation is “A Cancer Patient’s War on Cancer.” With that, Tony, I’ll turn it over you. Welcome. >>Thank you, Tony. Thanks a lot for inviting me. It’s great to be here and to tell you what we’re up to with our small but feisty startup called All4Cure. So, just going a little bit– providing a little bit of historical context, as Tony has mentioned, I’ve been in Seattle now for almost 30 years. And I was attracted to come to Seattle because of the Hutch and because of stem cell transplantation. And at the time, you know, now nearly 30 years ago, the idea, the concept of stem cell transplantation that I found so attractive was it epitomizes the idea of doing our very best for a patient with cancer, giving them tons of chemotherapy, giving them somebody else’s stem cells, and then trying to, you know, get them through the incredibly difficult clinical complications that can ensue in the hopes that they can live to an old age. And so you’re throwing the kitchen sink at somebody and then trying to rescue them, a very kind of dramatic, attractive clinical setting for me. And this is a picture taken during one of the early years now, 25 years ago when I was an attending physician at Fred Hutchinson with– at the birthday party of a little girl whose mother was getting a stem cell transplant. This girl’s mother had CML and she had an unrelated donor transplant because this is before the discovery of Gleevec. And sadly, what you don’t see here is her mother had developed a terrible complication with graft versus host disease and liver failure and she subsequently died. But the– And, you know, four years later or maybe 10 years later, she would have had, you know, dramatically the different kind of clinical course based on the discoveries of Brian Druker and others. So– But the idea of doing our best is very attractive to me. I’ve been a physician scientist, as Tony mentioned, at the University of Washington for almost 30 years, working in other areas. But about eight years ago, I switched my research focus from other things to cancer based in large part on hanging out with my wife, Sibel Blau, who’s a community oncologist down in Puyallup, Washington. And unlike me, where as a physician scientist, I do mostly research, see patients a little bit of the time, Sibel is in the trenches seeing patients every day, you know, sometimes, 35-40 patients a day. And in going with her to some of the ASCO meetings for the first time, I became convinced that patients weren’t getting adequate access to the dramatic advances that were available to me as a researcher, especially with next generation sequencing and things like that. And I used to tell people that I would have, you know, better tools to understand what’s going on in a mouse in my lab than Sibel would have an understanding of what’s happening to her patients. And so, that led into really a complete– a retooling of my research program to focus from other things on– to switch to cancer. And we made the center at the University of Washington called the Center for Cancer Innovation that’s based on a number of principles that are described here, where, you know, what does– and really, the overall question is what does it mean 25 years later, and now this is in 2013, so 20 years after that initial slide that I showed you. What does it mean in 2013 to do our very best for a patient with cancer? And so the Center for Cancer Innovation which is based on these principles to aggregate divergent areas of expertise, to transcend institutional boundaries, so anyone that could be helpful to our patients, we wanted to work with them, this idea of cancer, the data problem, and then removing barriers that exist between researching clinical care, fusing those processes, giving patients with an incurable cancer access to any advice technology expertise that could potentially be relevant to them without concern about whether this comes from the, you know, clinically validated realm or the much richer but much more speculative research realm as long as patients are informed and everybody knows what’s going on. And then the last part is to focus on the longitudinal analysis of patients with cancer. And so our main– And so, we had these get-togethers at our home where we would bring together people with divergent types of expertise in bioinformatics and community oncology and academic oncology and even pharmaceutical companies another diagnostic companies. This is my wife, Sibel. And also at this meeting, we brought this person, Ms. Angles [assumed spelling], who was a patient who had the type of cancer that we focused on called metastatic triple-negative breast cancer, as you will know, a miserable really difficult, incredibly difficult disease. And Nissa [assumed spelling] very sadly died within a couple of years of this picture, but the idea of integrating patients at the outset of what– in the process of what we were doing. And so, really the major work product from this effort was a clinical trial called the Intensive Trial of OMics in Cancer, ITOMIC-001, where– and the way that this works is shown schematically here where we would take patients with metastatic triple-negative breast cancer who are scheduled to receive cisplatin. And so these patients by and large are heavily pretreated and they and their doctors have decided that the next drug they’re going to get is cisplatin. Now later, we removed this requirement of cisplatin and now the trial is written in a way so that the patient is about to receive a treatment that she hasn’t received previously. And then we do multiple biopsies of multiple metastatic sites. And from those multiple biopsies, we subject them to an extensive analysis with, you know, whole exome sequencing later called genome sequencing, RNA sequencing, indeed sequencing of a panel of cancer-associated genes, put the information on the cloud, make it accessible to experts from around the world who can look at this information, help us decipher it to the best of our primitive abilities, and then we write a report that goes back to– we have a virtual tumor board. And then we write a report that goes back to the patient and her oncologist. And so the idea is to have this report ready by the time the patient has failed this initial treatment. And then if the patient and the doctor wish to follow any of the recommendations that we make, we work super hard to make it possible for the patient to receive the treatments that are predicted to work. So essentially, within each patient, creating a set of predictions, testing the predictions in the patient, and enclosing a learning loop that allows us to learn when we’re right or frequently when it looks like our recommendations don’t work. And we do this repeatedly over the course of the patient’s disease. Just showing one patient’s situation that was one participant in this trial that was described now a couple of years ago, almost three years ago, and this just shows for one patient, you really can do a lot. If you’re really– You know, if you’re– if you have a patient with this incurable problem and you really are trying to unleash the world’s resources to try to figure out what’s going on and come up with a recommendation that could be potentially be helpful to her, this paper shows what’s possible. And I would just say– And if you’re– if you have interest, you’d be– you know, I think this paper is interesting for a number of reasons. But for one patient, you know, we’re able to bring together tons of researchers from tons of different institutions. Many of these researchers had no prior involvement in patient care. And 18 researchers, we specifically recruited for this patient. One thing that came from this, I would say, from this trail now where we’ve enrolled 32 patients over the last five years is– we’ve learned, I would say, three big things which I’ll show you in the next couple of slides. The first is that– and as you will appreciate, every patient in this trial will be swimming in data. We barely know which way is up. And– But often, we find changes affecting genes that we think could be important to that patient’s tumor. This patient, for example, had a ROS1 mutation, a point mutation, not a fusion, but a point mutation. And so we sent an email to people that I knew or that I was able to get a hold off or that I knew from PubMed who are real domain experts in this area. And you just shoot them an email and you say, you know, here’s a patient with a– you know, that had this terrible problem, has a mutation in the gene that– where you’re one of the world’s experts, and can you provide any advice? And so– And one other things that we– one of the most gratifying things that we found from this trial is that when you do that, the researchers almost always answer, and they tell you everything they know. And this is– So here, we got advice from Al Charest in Boston, Frank Bohmer in Germany, and Lu-Hai Wang in Taiwan. And then the other interesting thing is, I had sent an email to David Baker, a super well-known researcher here in Seattle who didn’t think he could help me. But unbeknownst to me, he had forwarded my email to his colleague, Lance Stewart, who in turn forwarded my email to Dan Flynn who is the CEO of a biotech company called Deciphera. And Dan– Lance described Dan as the world’s expert regarding this specific issue. And so it’s– So I think that the power of a willingness of researchers to participate and the potential network effects can be really powerful. The other thing that we learned is we asked patients, why do you let us do this? You know, we’re putting patients through a lot, a lot of biopsies and stuff like that. And we found in this paper that was published last year in JCO Precision Oncology from a survey of the first 15 participants, we found, you know, what are the main drivers of participation? And the motivations are– These are the two strongest motivations. First is that patients hope that we can find something that would be helpful to them, even though in the consent process, we really try to be very clear that I’m not at all confident that we can provide a suggestion to them that would give them a better outcome than they would get by just seeing their oncologist as part of standard of care. But then the equally stronger, perhaps even slightly stronger motivation for participation is that the hope– is the hope that their experience with cancer can transcend their own lifetimes to help other people. And then if you look at, you know, the things that patients are least worried about across these, I think, 17 survey items we looked at, was the loss of confidential information. There was really generally very low level of concern about that. In the– So then in April of 2015, I’d had a few months of hip pain. It wasn’t really hip pain. It was more like hip pointer-like pain, like you get in a football injury. And finally I got an x-ray which showed this big hole in my pelvis. So I knew kind of within a few seconds of getting this x-ray that I had cancer. We found out the next day that it was myeloma. You can get a better look here where on a CT scan, I have a big plasmacytoma kind of erupting through the cortical bone, mean-looking thing. And I– Then, we kind of immediately contacted my friend and colleague, Pam Becker, who’s a colleague and hematologist physician scientist at the University of Washington. This is her husband, Marc Stewart, who’s the medical director at the Seattle Cancer Care Alliance. And so, that evening after– so, I think I got the x-ray on Thursday. Friday, we had the diagnostic test, called Pam, and then Pam and Marc came to our house that night with a bottle of red wine and a Boston cream pie, I think the Boston cream pie was somehow Marc’s idea, and Pam then took care of me. And we applied in me the same approaches that we had been applying in our breast cancer patients. And this was discussed in a New York Times article that I think just– I’m so grateful to Susan Gubar for highlighting this. But I had then tons of different biopsies of the plasmacytoma, like 22 biopsies of that, sequenced three different regions of the plasmacytoma. I had also isolated myeloma cells from elsewhere in the bone marrow and sequenced those, found some pretty interesting things. One thing that we found that was actually clinically relevant was the plasmacytoma. Myeloma cells and the plasmacytoma had a cytogenetic change that’s associated– that kicked me out of the best prognostic category and put me into an intermediate prognostic category, a one-two copy gang that wasn’t present in the myeloma cells in my bone marrow. But looking at my course as a patient, you feel like you are– This is from an article that I wrote at in the Cancer Letter earlier this year describing the choices that I’ve made as a cancer patient. You know, you’re confronted with these choices, you make your best decision, and then you keep going. And as a patient, I think perhaps the most important insight to me as a patient has been that I feel like I’m in this 1960s TV game show called “Let’s Make a Deal”, where patients are– where I feel like I’m confronted with three doors. You know, behind door 1, a new car, door 2, trip to Bermuda, door 3, a goat. And as a patient, you feel like you’re confronted with these choices, you make the best judgment that you can, you go down the trail a little bit, and then you make the next set of choices. And the point is that I’m not the first one to confront these decisions. Thousands of people have preceded me in making these choices and experiencing the consequences of those choices, yet their experiences are not available to me. And that’s the lost information that All4Cure aims to capture. So when– So after I got diagnosed with myeloma, I got the standard treatment, I responded, I went on to get an autologous stem cell transplant and then an allogeneic stem cell transplant, which is somewhat controversial, but I ended up having a match brother within Seattle, probably the best place to have this procedure done. And I did– And it’s a longer story but I decided to do that. And while I was on medical leave of absence, I started this for-profit company, All4Cure, which is building a knowledge-sharing platform that I’ll talk about now for the rest of my talk. But the basis for All4Cure is that at least 95% of the information from treating disease is lost, patients get treated, they respond or they don’t, and collectively, we don’t capture any of that information. And it works– So– And All4Cure is focused on capturing information from all patients. We’re focused on a blood cancer called multiple myeloma, not just because that’s what I have, but because it’s an easily monitored disease with frequent blood tests. It’s estimated that there are about 130,000 patients in the US. It’s currently about 30,000 new patients a year. And there’s an explosion of new treatments. As many of you will know, 19 FDA-approved drugs, four approved in 2015 alone, dramatically improved life expectancy, but nobody really knows how to best use these treatments and the sequence on the patients that are best suited for a given treatment or combination of treatments. So, while I was on medical leave of absence, I was working on this and we started All4Cure now just almost exactly two years ago. And we launched our minimum viable product in March of 2017. And as of today, we have more than 600 registered users with more than 350 myeloma patients, 50 clinicians, and 50 researchers. And we have many examples of patients having benefited from their participation. I’ll just– And I’ll go through some of those in just a few minutes. So the steps for getting involved in All4Cure are to go our website, register, which is free, participation is free to everyone. And then if you’re a patient, you also allow us to access all of your medical records and irrespective of which institution you’ve been at. And we try to get the medical records from every place where patients have been seen. And from the medical records, we extract a structured dataset that shows all treatments and all responses. And you can’t see here because this is just the slide but hopefully, we’ll have a minute to go on the website. And what you can see here is my experience with myeloma from diagnosis to present. And you can hover over these icons to see these specific treatments. This is my autologous stem cell transplant, my allogeneic stem cell transplant, and then these are tumor markers that give an indication of the extent to which these treatments are working as we would hope. So this graph– this is a graphical depiction of my experience with myeloma. And then beneath this is a summary, a narrative of my experience. The documents panel allows PDFs to be uploaded which can show my foundation medicine report or any other number of reports that can be posted there. And then this thing is a key feature, this discussion panel, where I or any other participant in our platform can look at my situation and post comments. And so this combination of structured data extracted from the medical record plus a discussion panel allows for a 360-degree view of both patients reported outcomes and structured data from the medical record. And I think that has many important applications. So, I think there was one other thing I wanted to mention about this but I’ll come back to it. It slipped my mind at the moment. So I’ll show you a few examples of how this has been helpful to patients. And I’ll just show you three examples here, but there are many other examples that I could talk about, but in– but these three examples highlight different ways in which patients can benefit. And so, this is the dashboard, the graph from the dashboard of a patient that we call MM-80. Oh, I remember what I wanted to say. Patients– This is not a clinical trial. Patients participate by agreeing to our terms of service and privacy policy and they allow us to display this information here, and this information is not HIPAA-protected, and they agreed to that by agreeing to our terms of service and privacy policy. So MM-80 is a 61-year-old Alaska Airline flight attendant who developed myeloma in the summer of 2016, so just a little more than two years ago, and she had really aggressive cytogenetic features. So the prediction was that she was not going to do well with conventional treatment. And so she was treated initially, I think, with KRd, Car-Revlimid-Dex, responded, and then we sent to Fred Hutchinson Cancer Research Center and the Seattle Cancer Care Alliance for two stem cell transplants, an autologous stem cell transplant followed by an allogeneic stem cell transplant from her matched brother, so a treatment very similar to the treatment that I received. But before she could get the first of those two transplants, she developed a terrible complication of her myeloma which is unfortunately rare, but myeloma cells had penetrated and entered into the spinal fluid. And this is a miserable complication that they tried to treat with repeated intrathecal chemotherapy treatments, but that didn’t work. The cells didn’t go away or they didn’t go away in a lasting way. And so, after many attempts, the patient was told, I’m sorry, we can’t proceed with these transplants and we sent back to her oncologist who happened to be my wife, Sibel, saying, you know, we’ve set her up for hospice because there really isn’t anything more we can do. And so we sent an appeal to our experts and we got a number of different suggestions about what could be done in this situation. Dr. Travis Quigley of Bluebird Bio indicated that she would not be eligible for a carticel treatment based on the concern about CNS toxicity and perhaps an exaggerated likelihood of CNS problems in a patient that already has preexisting CNS disease. Bill Bensinger, a world renowned myeloma expert here in Seattle at the Swedish Medical Center, recommended consideration of Part B of Hyper-CVAD with the idea that the drugs that are associated with that can penetrate– can have a high likelihood of penetrating into the spinal fluid. And then we got this suggestion from Ken Anderson who suggested an experimental drug called marizomib, which is a lipid-soluble proteasome inhibitor acquired by Celgene last year. It’s experimental, but Ken had shown in a paper just a couple of months before this post that it had– that marizomib had worked in a couple of patients with CNS myeloma that they had treated. And so, the idea that Bill Bensinger suggesting Ken Anderson’s suggestions– well, what I should say is I should finish the story because I won’t to be able to show the rest of this, is– so the– we tried to pursue Ken Anderson’s suggestion. And in the course of trying to get marizomib, the patient was treated according to Bill Bensinger’s suggestion with Part B of Hyper-CVAD, and that resulted in clearance of the cells from the CSF and the patient was able then to proceed to her autologous transplant and her allogeneic stem cell transplant. And the point is not just that we can bring a lot of expert opinion to bear on the problems of one patient. I think the larger point is that Ken Anderson or Bill Bensinger’s suggestions in a one-on-one phone call or email exchange with my wife affects one person where their suggestions in this transparent network of patients, clinicians, and researchers can have a dramatically amplified impact. And that’s essentially what we talked about there. So the second example is a patient that we call MM-105. We have to find a less kludgy way of referring to patients. It’s a little bit too clinical and too sterile. We’re working on that. But MM-105 is a 70-year-old PhD of biology who lives in San Diego who is diagnosed with myeloma in the summer of 2015, was treated with Bortezomib, Decadron. This is Zometa. And she responded to that treatment but her M protein, which is shown here in this blue line, never went down to zero. It was still detectible. And so after she registered for All4Cure, she contacted me and expressed some concern about the communication between her primary oncologist that she would see every couple of weeks and the myeloma expert that she would see every six months. And they didn’t seem that– there didn’t seem to be a lot of coordination in her opinion between those two physicians. And I asked her, you know, by the way, why aren’t you getting Revlimid or lenalidomide, which is now a standard of care. Three drugs for myeloma is now standard of care. It was a little more that hadn’t been as clearly established when this patient started treatment. And the patient MM-105’s response was what’s Revlimid? And I said, well, I can’t tell you that you’ve been treated incorrectly, but what I can tell you is comparing– is that looking at the dashboards of 60 other patients that were currently– that were participating at that time, you’re an outlier. Everybody else in your situation is getting Revlimid. And so she decided to switch oncologists. She asked for our suggestions for two other oncologists in her area. Through an expert network, we sent her two names. She saw both, chose one, and ended up on three drugs that include Revlimid. And so this is an example of democratizing knowledge, where a patient can know how his or her treatment compares to thousands of other patients in a way that is not constrained by geographic location. The other thing that this patient situation has demonstrated is the potential for the All4Cure platform to be a potent tool for patient education. Patient asks a question here and one of my colleagues, a physician scientist at the FCCA, David Koffey [assumed spelling] and I responded to this. I don’t show that response. And then the patient also described after getting the first doses of this new treatment some initial toxicity that she was experiencing, thereby allowing us to also capture patient-reported outcomes. And then the final example that I’ll talk about, I’d like you to see, well, there many other examples but the last one that kind of shows a distinct, I think, attribute of the participation in our platform is MM-8. And MM-8 is a 56-year-old guy who is diagnosed with myeloma in March of 2015 and he has a 17p deletion and he didn’t respond to initial treatment with Bortezomib, Decadron, and lenolidomide. It just didn’t work for him. So his doctor switched him to a different chemotherapy regimen, Carfilzomib, Pomalidomide, and Dexamethasone, and that did work for him. And then he went ahead to get an autologous stem cell transplant, which is kind of a very standard treatment. And then his maintenance was maintained on Car-Pom-Dex for the next 18 months doing well. As you can see, his spike looks like it’s nicely under control with this treatment. So he contacted me this past February, saying, you know, two weeks ago, I got a letter from my insurance company saying that they’re not going to pay for Car-Pom-Dex. They are referring to this paper that says, you know, I can get RVD, Revlimid-Velcade-Dex for my myeloma, but I can’t get Car-Pom-Dex because there’s no paper that describes it and no NCCN or ASCO panel guideline that would endorse this type of approach. And so, he had appealed that decision, his physicians had– his physician had appealed this decision, and the insurance company denied that appeal. So he asked if we could help. And so we put together our letter that included this visualization of the patient’s course showing that RVD didn’t work, showing that Car-Pom-Dex does work. But then in the same letter, we included the graph from MM-77’s dashboard. And MM-77 is also a guy in his 50s who also didn’t respond to initial treatment. And this, I think, was with RVD, but then his doctor did switch to Car-Pom-Dex. He got an autologous transplant, and he had been on Car-Pom-Dex then for the ensuing nine to 12 months. And this patient’s oncologist had independently arrived at this exactly same approach. So by including MM-77’s dashboard, we could tell the insurance company, hey, MM-8’s oncologist isn’t, you know, out to lunch doing crazy things. Here’s a different oncologist who’s independently arrived at the same approach and it’s working for this patient. And based on that, then the insurance company approved the appeal. And this raises the larger question of how do we make these decisions? How do insurance companies– how should they decide on what to pay for? Or what treatment regimen should an oncologist decide to use in their patient? And right now, we’re kind of constrained by the result of consensus panels, NCCN, ASCO, or publications. But what if we could base these decisions on real data based on the results of our collective experience to know what works and what doesn’t? And so, these are just some summary points of what I think the benefits are. And so, this just shows some of the features that patients, you know, what could patients do before All4Cure? As a patient, you can request your medical records. You can review your lab results through patient portals. You can read about your disease, including treatment options and prognosis. You can read about new developments. You can consult your doctor, see second or third opinions as many patients do. And you can participate in disease-related social media platforms. And some of those are actually really quite impressively run. Whereas– But now with All4Cure, we can provide access to a comprehensive, easy-to-understand graph that summarizes your entire experience with cancer. We can allow patients to compare themselves, their own tests, treatments, and responses to now hundreds of other patients. And we can allow patients to request other information or suggestions that are specifically relevant to their situation. Oncologists can benefit because before All4Cure, of course, oncologists can read their patient medical records. They can review the literature. They can present patients at the tumor boards. They can consult colleagues or refer patients for second opinions. And with All4Cure, then oncologists now also find value and access to this comprehensive portrayal of what’s happening with the patient. They can also look at the graphs of other patients and see how other oncologists do things. And they can review suggestions or request input for suggestions from other participants. So, in plotting– as I’ve mentioned, All4Cure is a for-profit company and I’m going to just say a couple of things about the– about how we aim to generate revenue. But in thinking about this, you know, kind of establishing first principles, I think it’s incredibly important that we be cognizant of the fact that our unwavering loyalty will always be to the very best interests of our patients. And in generating a for-profit company, we have to be especially on guard for the potential for mission [inaudible] to come in and put us in some way out of total alignment with the best interests of our patients. And we have to incredibly cognizant of that and make sure that we never lose sight of our core mission. And so, these are some of the core principles where we will help patients who participate in our platform who entrust information to us in whatever ways we can. Do we– Another principle is transparency. So as we enter into commercial relationships, we make those apparent to everyone that’s participating in the platform, the concept of equality that every patient will have equal access to every other All4Cure participants. And then this is a really key one, I need to find the cool icon for this, but the idea of respect. So, you know, we’re getting like detailed deep views into what’s happening to our patients. And, you know, And we– I’m guessing about this, but I’m guessing that we’ve probably seen, you know, progress notes from at least 100 different oncologists and you quickly see, you know, that there are huge variations across those notes. And once in a while, we find something that can be important that maybe there’s some bit of input that we provide could really help a patient. And so kind of a relatively common thing would be to say, you know, this patient might, you know, benefit from Zometa, if Zometa isn’t being given. And that’s not a very uncommon recommendation that we would give. Or, you know, probably the most– one example of a real error would be that, oh, there was a patient– we’ve had a patient where the patient was on the lab tests known to have an IGM, monoclonal protein extending back several years where the oncologist’s notes indicate that it’s an IGG monoclonal protein. And we can– You know, and there are biological reasons why it would be important to know about an IGM, that it’s an IGM rather than an IGG. And in this situation– And this is– Similar things have probably happened maybe 68 times since we started where we find situations similar to that. And in those situations, I’ll personally call the oncologist, introduce ourselves, and just mention, hey, you know, we were just looking through the patient’s progress notes and it looks like, you know, we see in the progress notes, it looks like the thought is that the patient has an IGG monoclonal protein. But looking at the labs, it seems pretty clear that’s it’s an IGM. And probably– And then I can tell you in every instance where we’ve done that to contact the oncologist offline, they’ve always been appreciative of that. And so the idea is, you know, we’re not here to look over anybody’s shoulders. We’re not trying to impose ourselves in any way on the doctor-patient relationship. You know, in terms of service, we tell patients, we are not providing medical advice. We are rather trying to serve in the role of a knowledgeable friend that will raise suggestions that you and your oncologist may wish to consider. But I think, you know, as we move forward, these– maintaining unwavering adherence to these principles is core for us. And so, how are we going to make money off of this? And so, the thought that we have kind of in two large areas are shown here, where as many of the people that are in attendance will know what the 21st Century Cures Act is and the idea of this expansion of so-called pragmatic clinical trials. And I think the All4Cure platform can be an incredibly powerful way to make the clinical trial participation, the process of participating in clinical trials a much more democratized easy– easier series of events than is available currently. And so, this– our initial, I think, area would be for– for request for expanded indications for approved drugs. So if you’re looking for– if a drug company is interested in testing drug x and drug y together, and one could– and if there is an existing data of sufficient robustness to know whether that combination works, you could imagine a situation where when both drugs are approved, any oncologist anywhere who has a patient who wants to participate in this could enroll. Their patient could enroll. We could capture the information, I think, in a much more cost-effective way than is possible currently. And then the idea of using this also for Phase 4 monitoring, looking for a response in the toxicity profiles of patients that are getting approved drugs going forward. And then really, you think probably that the larger opportunity for us is in the idea of using the All4Cure platform to promote value-based care, to identify areas of variation, to try to standardize for those, and eventually the– eventually develop a way of making the decisions that underlie cancer treatment much more data-driven than they are currently. So this is just a little bit more information about the 21st Century Cures Act, the incorporation of real world data into FDA decision-making. And this is a slide that I’ve just purloined from Sean Khozin at the FDA that describes really the idea that results from pragmatic clinical trials may not only be cheaper and more efficient, but they may generate better results than are available through traditional clinical trials. And here, the idea is that in conventional clinical trials, patients typically have to pass through a very stringent set of entry criteria. They’re typically seen at centers that are able to support those trials. And when we– And then when the results of that trial come out, which have a high degree of internal validity, so we’ve really pushed the scale toward making sure that internal validity is high, now when you extend those findings to just regular people out there in the world, a lot of times, you can find that things don’t work as well in the real world as they might have in your narrow highly-controlled environment. And so pragmatic clinical trials can definitely– should be able to address this central concern. The other concern that happens with clinical trial participation is that patients drop often. This is just a slide that I took from one of this sites, showing that, you know, a test they may that maybe a third of patients who enroll in clinical trials subsequently drop off. And what I can say about that is I think the core advantage of All4Cure compared to any other way of doing this that I’m aware of, is that we are tied at the hip to our patients. And we can follow them throughout the entire trajectory of their disease, so if a patient moves, a patient goes to another doctor within their neighborhood, you know, other efforts to capture that data can fall short, whereas we can stick with the patient throughout the entire course of their disease and hopefully have a dramatic impact on reducing the likelihood of patient dropout. And so what we are really aiming for in the larger picture is to make a Waze on how we get to the traffic navigation app for cancer. And so a patient would be able to look at the treatment options that are available to him or her, would know what the success rates and what the toxicities are associated with those different options, make an informed decision, and have their experience added to this ever-growing body of knowledge. And these are kind of some higher-level analogies between Waze and All4Cure, both of them are based on this idea of collective intelligence of both our– for All4Cure, we’re trying to navigate to the most efficient route to wellness and we can anticipate hazards in a way that’s analogous to All4Cure. And then here, I just wanted to make– I’m going to just, for one second, go to the website. OK. So I’m doing OK on time. So people might wonder, hey, what happened to the breast cancer patients that we have because we’ve made this dramatic switch from metastatic triple-negative breast cancer to myeloma? So, to allow us to continue this work for– and we have this fair amount of momentum here regionally for patients and doctors who like what we’ve done in our clinical trial, we’ve now created a clinical trial within All4Cure. So like I say, All4Cure itself, to participate, you don’t, you don’t participate in a clinical trial. But we have now four patients who want to– And this is really right now confined to our breast cancer patients. This allows us– if you agree to participate in our clinical trial, we can post all of the results from all of the research-based– or any sort of diagnostic test that we do on your dashboard. And we can– And you allow us to do that in the context of this clinical trial for a consensus view– or not necessarily consensus, but an aggregate look at what’s going on with you, trying to gather the world’s experts to look at your situation and make comments. And this is still somewhat rudimentary but I’ll show you– just the way that we’re using this right now for a breast cancer patients is you can see here, breast– you know, solid tumors are more difficult because we don’t have these nice zero markers for the stage of disease. This is showing all of the treatments for this patient. And we have some radiographic imaging that we’re showing just in a more boring kind of narrative version of what’s been seen. We’re looking for ways to do this better. But– And then now, kind of carrying over what we’ve done in our study at the University of Washington, we’re posting the results of tumor board, this virtual tumor board on the patient’s dashboard for review by anyone who might want to, you know, have input. And then the last thing I’d like to say is I’d like to I just, for a moment, mention the incredible level of indebtedness I have to this person, Prof. George Stamatoyannopoulos, who many of you will know, a real pioneer in the field of human genetics and my mentor along with his wife Thalia Papayannopoulou. And George died this summer, this past summer, but, you know, a profoundly important influence to me. It’s hard to overstate how important George was– George and Thalia have been to my career, and I’m incredibly grateful. And that completes my comments. >>Let’s thank Dr. Blau for a very poignant and amazing presentation. [ Applause ] Well open the floor for questions, if you have a question here in the room, just raise you hand and likewise if you’re on WebEx, use the WebEx dashboard to raise your hand and we will unmute your line. So questions here in the room? >>There is a question online, how do MM patients sign up?>>OK. How do MM patients sign up? It’s a question from online.>>So it’s a two-step process. They have to– They go to, you know, our website www.all4cure.com and they can just click on Join Now. Let me– It’s pretty straightforward. It’s– I can’t say that’s it’s perfect. But if you just log out here, we can see, you know, and now patients, so this is what somebody would see at the top of when they come on to the platform, this Join Now button. You put in your email address, username, password, repeat your password, first name, last name, your role as a patient, you have to agree to our terms of service and privacy policy which indicate among other things that you’re not going to try to identify other participants, you’re not going to post anything mean, you say you’re not a robot, you sign up. And that gets– that will bring you to another data field with a few more questions about whether you have myeloma or breast cancer. Answer a few more questions in your end. And then the other key thing, essential thing is to get access to all of the medical records. And so, there, we have on our home– on our front page, patients can download a HIPAA release form. We’ve been trying to take as much of the burden off of patients as possible. So when a patient registers, we’ll shoot them an email that includes a DocuSign version of our HIPAA release form, and patients then can just do the DocuSign that get– and we do one for every institution where the patient has been seen and then we send it to that institution as you might imagine. And we’ve done this with over 150 different institutions. As you might imagine, some institutions don’t like our HIPAA release form. They want their HIPAA release form or they might not like an e-signature, they want the patient’s signature, or they don’t want to receive it electronically. They have to get it by US stamped mail that shows up, you know, at their doorstep. So, you know, we go after everybody and so with 150 places, we have a fairly substantial database of what works for different institutions. But we try to take as much of the heavy lifting off of the patients as possible. >>Tony, there was a lot packed into your talk here and it’s like I’m not even sure where to start with this. But, you know, you started off– when you were first starting with the power of networking and just getting, you know, oncologists from around the globe to weigh in on what, you know, their experience with the types of patients that were being seen, and then you sort of wrapped it up in this concept of collective intelligence, and this clearly can be very powerful for patients. You also talked about patients being able to– or willing to share their data and we understand the importance of that as well, and I think this model of having not HIPAA-protected data and being able to share these data as being very critical as well. We– Certainly, we here at CBIIT and broadly across the NCI understand that cancer is a big data problem and we’re working on, you know, working on some efforts in that direction as well. My– I guess with those comments, my question to you is how do you see this scaling? How do you see this All4Cure model scaling beyond just the triple-negative breast cancer and the multiple myeloma? What are your thoughts about that?>>Well, so, yeah, right now– That’s a great question. The scale question is something that we’re intensely focused on. So we, you know, we are quickly moving to incorporate just patient portal data. So, for example, the lab data that we get is pretty easy to get. You can get that from patient portals. So this, you can see, you know, these are again my dashboard, you can look at all of my labs over time, but most of that is in, you know, structured data that can be fairly readily extracted just from patient portals. IV medicines can be– you know, sometimes are pretty well-recorded in the medical record. Oral medicines suck, they’re in– they’re very poorly recorded. You can see when a patient has got on the prescription but then, you know, what that really requires is going through the doctor’s progress notes, really trying to figure out what’s happened in a patient, when there’s an interruption, we want to capture that. Our goal here is to make the most granular, accurate, and comprehensive depiction of what’s happened to a patient as is possible to assemble. And so this is, you know– So eventually, this will be replaced hopefully by medication adherence, so apps that allow, you know, a dot to show up here the moment that a patient indicates that they’ve taken a given medication. So I think, you know– And then, you know, and then I think the whole natural language processing field is, you know, super important, but on the other hand, just very rudimentary compared to the demand of really trying to make sure that you get this type of information right. So patient portals are the first way. The second thing is to incorporate tools that make it easier to go to the medical records, to the parts of the medical records that indicate, you know, the focus in on for example when the patient was taking this drug. But I can tell you sometimes we get, you know, we get medical records however the places will send them to us. And at times, this has ended up being 10 boxes of, you know, 6,000 pages of medical records that we scan, upload on this share file. You know, one of the consequences of the 21st Century Cures Act is that hospitals are going to be required to make that data much more readily available in an electronic form than it is today. But I think, you know, as things exist today, I think we can, I think, readily scale to become, I think, five x more efficient than we are now. But if we’re trying to really– you know, dedicated to trying to get this right, then I think we are going to always need really knowledgeable people who are committed to doing this, and making sure that we’re looking through things to get it as right as possible. And then of course the other advantage that we have is that when there are questions, we can go directly to the patient and ask them to clarify these things. >>Right. And that sort of led into another question that I had, is that how do you actually do the data extraction and it sounds like there are multiple approaches that you’re taking but maybe you could talk about that a little more?>>Yeah. So medical records, I’ve kind of described the worst case scenario of, you know, paper records showing up at the doorstep. We have other, you know, many– that’s fortunately fairly rare, we get electronic PDFs from a number of places that are searchable. You know, that’s much, much better. And then in some situations, we have practices that have– with whom we signed agreements that allow us to access the patient medical records for patients who would have agreed to participate. And that’s a much more facile, faster way of doing things.>>Great. I think we have a couple more questions online. >>Yes. So one question is, is there a cost to patients? And then–>>No.>>– in the family–>>No cost. >>No cost? OK. And can a family allow use of a loved one’s information postmortem? >>So we have– So the second question has come up. So– And we have– we’ve had patients, of course, who have participated and who haven’t, and who now have died. And in those situations, the family members many times have been very interested in making sure that we get all of the information from them. I think, you know, from our vantage point, yes, absolutely, patients, you know, family members who would be willing to allow us to access the medical records of patients who have died, we’d be very interested in posting their information. Right now, the other bit to that though that I need to add is that, of course, our priority is to focus on patients where we think we might be able to have an impact. So, I think– And right now, we’re a super small, super lean organization just kind of trying to do our best with a team, we have a team of 10 really smart young people that are– that we meet with and talk, we meet together, discuss patient cases and to make these structured datasets. But yes, absolutely, we’d be interested in talking with anyone that– that their loved– that would be interested in having their loved ones’ data be part of the platform. >>Great. >>Thank you very much with the extremely great talk. I was actually–>>Oh, thank you.>>That was your– And I have to apologize. I missed probably the first 10 minutes. There may be potential damage, I apologize. Number one, do you do any integration with patient advocacy in your organization like the multiple myeloma, when this comes to mind? This is number one. Number two is, where the bottleneck right now? Is it– Do you actually have too many candidates that you have to actually kind of scale up? Do you actually process the data and get them in their actual format? Or is it– So that would tie back to the patient advocacy resource. It’s more a recruitment problem, you could handle more. It shouldn’t be more difficult to get those people on board. >>Yeah. That’s a great– OK. Can I answer this one, so I don’t forget it? >>Yeah. >>So, you know, we would just love, love, love to collaborate with patient advocacy groups. You know, MMRF is kind of the shining star of what’s possible with a not-for-profit organization. And the IMF, its global reach, the International Myeloma Foundation, you know, incredible, incredible organization. So we’re very interested in working together with those organizations. We haven’t made– I would just say we probably haven’t had the bandwidth to make as much progress on that front as we need. And then I would say we’re at the point now for the first time of seeking outside funding. And I think that’s– So funding right now so that we can hire the people to, you know, get more patients and get and make this more automated than it is now is probably our main bottleneck. >>So, the follow-up question is with respect to that you alluded to when you said you actually help people to get reimbursement decisions, reversal for them. So– And obviously, you have a platform that’s totally emerging as of a real world evidence as they call it, right? Sort a trial– it’s not a trial but it is potentially once you are abstracted out, working in a similar way, is there some tie-ins with insurance companies or with the FDA to kind of, you know, bring this in the right direction so it can actually influence goal standards reaching care as well as reimbursement decisions? >>I agree with that.>>And what I meant is, logically there– of course, everybody makes their connections, but I was wondering, is there something that is more structured? Can you– Are there opportunities for you? Are you pursuing opportunities to formalize this? So this is a very actively outreach to FDAs or even to payers?>>Yeah. So, you know, I’m trying. So I’ve had discussions with some insurers, we’ve talked about the potential for pilot projects that would, for example, asses patient satisfaction. I– We just had a meeting with Sean Khozin earlier this summer and had a chance to show him what we’re up to. You know, we would love, you know, to participate, you know, deeply in those initiatives. Greg Simon at the Biden Cancer Initiative, you know, has been generous enough to hear about what we’re up to and they help think about how we can kind of make this more widely known. So– But it really is– I think on those fronts, it really has to do with bandwidth and just– you know, we have a really tiny workforce now to do a ton of work. But we’re super interested in those things. >>Thank you. Thank you very much. Yeah. Great, Tony.>>Thank you.>>Fortunately, we’re out of time. We’d love to continue the conversation more but we are out of time and– >>Sure.>>We’ll certainly follow-up. And I would recommend [inaudible] took the time yesterday to go back and look at your TEDx Talk from several years back and I would recommend that to people to go back and take a look at it as well.>>Thank you.>>That being said, I hope everybody can join us in our next presentation which will be on September the 26th when Dr. Rob Smith from the University of Montana will present here. And once again, let’s thank Tony Blau for this really fantastic presentation. [Applause]
>>Thank you, thanks very much.