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Aimee Martin (Host 1):  Welcome to the Oncology Soundbytes, a podcast produced by the Seattle Cancer Care Alliance designed to offer byte-sized audible oncology education from one of the top cancer treatment centers in the nation. I'm your host, Aimee Martin, a Senior Physician Liaison at the Seattle Cancer Care Alliance, joined by my cohost, Dr. Jason Lukas who's a Medical Oncologist and serves as the Medical Director of SCCA, Issaquah. Great to have you here, Dr. Lukas.

Jason Lukas, MD, PhD (Host 2): As usual. Great to be here, Aimee.

Host 1: Fantastic. And we're so glad to have you represent our community oncologists and really engage in clinical dialogue with our guests. And speaking of guests, I'd like to introduce Dr. Mohammed Sorror, Associate Professor and Physician at Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance and University of Washington who specializes in blood and marrow STEM cell transplantation and cellular therapies. He's here to discuss BMT specifically in older patients. Welcome to the show.

Mohammed Sorror, MD (Guest): Thank you.

Host 1: It's so great to have you, and I'm going to go ahead and turn this over to Dr. Lukas, who can take it from here and ask our first question.

Host 2: Yeah. Dr. Sorror, thank you so much for being here. It's a real pleasure to interview you. You know, I was just wondering first, you've had an amazing journey in your life to come here to be able to practice what you're doing. Can you tell us a little bit about your background and how you found your way into medicine?

Dr. Sorror: Absolutely. Well, my father was diagnosed was one of the common blood cancers, which is non-Hodgkin lymphoma when I was in the early years of my childhood. And I kind of witnessed through my childhood his struggle with treatment. And then the final outcome, he passed away when I was six years old because of the cancer. And I think that kind of inspired me to subconsciously, I would say, pursue a career in medicine and specifically in oncology. And interestingly enough, I ended up specializing in STEM cell transplant, which is, probably the only curative treatment for many types of blood cancer.

And because I'm also very interested in what else can be done above and beyond current practice, I naturally became interested in research. Because I think that's the gate to improve, to continually improve our outcomes of patients. And Fred Hutchinson Cancer Research Center is one of the pioneer centers in research about transplant, about STEM cell transplant. And that's why I was motivated to take the journey from my country of birth, Egypt, and travel and establish my career here at the Fred Hutchinson about 19 years ago.

Host 2: Just about the time that the first Nobel Laureate was doing all his work. Well, maybe a little bit before then. That is an amazing story. I can tell you that I feel the same way about my journey into medicine too, because my father was diagnosed with a total of three separate cancers. So, I appreciate the story and I'm sure that loss still resonates for you. How do you think though that you've seen changes take place in transplantation? How do you think those have affected patients? Because I know from my standpoint, as a medical oncologist, that we always think of patients over about 65 as too old for transplantation, but clearly you and your research has been sort of turning that on its, on its head to some degree, which has been really of the great things that you've done.

Dr. Sorror: Yes. So, I think, first of all, we have to give credit to many of my colleagues and some of them who started in this career way before me, where the transplant field has moved to what's called mini transplant or less toxic transplant that can potentially be tolerated by older patients. And that kind of opened the gate for myself to build a career about how to best understand the risks of transplant for the older population, given that up until late nineties, transplant was not an offer for them. So, one of the main things, over time that we tried to develop and understand is how to measure risk, is how to understand how each patient is different, when it comes to a procedure like STEM cell transplant. What are the specific factors related to each patient that can shape the probability, the risk, how the patient will do with a transplant.

And that started by developing the first model, actually in the transplant and the STEM cell transplant field that can take the patient history and clinical status and all their medical problems that the patient might have faced before and try to put it in a model that gives numbers and these numbers translate into risks and just tell the physician and the patient as well, here is the expectation from transplant based on your history, based on things that are related to your health. And once we call it other medical problems, other than cancer. And based on that model, you can tell a patient that well, transplant seems to be really safe because the expectations are really good of that outcome.

Or you can tell a different patient that we think transplant might be a risk, but we can do additional things to help you tolerate the transplant. Or you can tell another patient, maybe transplant actually is too much of a risk and other treatments could be better. I think developing that model, which came up to, in 2005 have changed practice dramatically across the globe worldwide, because it has been adopted by transplant centers in many countries. And physicians use it regularly to evaluate risks of patients before they go to transplant. And because of that, now we kind of have more confidence about what to expect when we offer a transplant to older patients.

Host 2: Yeah, exactly. I mean, I think that's, to me, what struck me about your work that I thought was really outstanding is before it was always just a bit of a thumbnail sketch, you'd say over 65, maybe with a couple of co-morbidities. I don't think that's good, but as we all know, with physicians, it's like herding cats, right? Everybody's got a different opinion and a different take on an individual. And so, these sets of rules effectively that were put together, kind of codified a list of things that are important versus the things that are not so important and are able to give both physicians, the team, and maybe most importantly, the patient a good sense of what their chances are if they decide to embark on that kind of journey.

Dr. Sorror: Yes, absolutely. Try to use more objective information, more unified objective information that we can assist all patients based on them.

Host 2: Exactly. Exactly. And so what we're thinking or what comes out of your research now, is that you know, as I said before, historically over 65 was going to be difficult. Do you feel like you have any top-end age limit for a patient these days?

Dr. Sorror: I try to advocate for the idea that age is just a number because over the past two decades, what we've learned is there could be patients that are above 65, above 70, or even above 75 years old, who might do actually as good as younger patients or even better, because their biologic age, their physical age is actually young. On numbers, they may count 60 or 70 years old, but physically, they perform and present themselves as younger and healthier patients. So, advocating more for the idea of use these subjective measures to calculate the biologic age of a patient. And, and because of that, I think the oldest patient that I've seen in the clinic and recommended transplant was 79 years old. Now these are exceptions. There, there are older patients who transplant is not a good option for them because we know from a natural history of diseases that as people get older, they're more likely to pick up other medical problems. But there are these exceptions.

There are these patients where their only problem is cancer or their only problem is cancer and something else. And these patients tend to do way better than the patients who have in addition to cancer, multiple medical problems that affect their heart, their lungs, their liver, their kidneys, or other organs. They could be young, they could be in their forties, but these medical problems play a big role in how they will tolerate the transplant or how successful the transplant will be like. So, to answer your question, now when we see patient above 65, we evaluate their medical problems. We are now actually doing more research to expand our knowledge.

So, it's not just the medical problems, but we look at other things, such as how about the psychological health? If they have depression, how about their physical health are they able to manage activities of daily living on their own, or they need some help? How much walking they're doing during the day, how fast they walk, what's called gait speed, which is one of the most effective objective tests to measure life expectancy, believe it or not is how fast naturally people walk can get a lot of information about life expectancy and about health.

So, since the time when we developed and published this new model, the comorbidity index in 2005, until now, we have added way more information that increased, that is kind of a wealth of information about how to better assess older patients for transplant. And I would say that we here at the Fred Hutch, we took the lead in developing these, these mechanisms and systems and using them in assessment of risks and heath.

Host 2: Very impressive. Very impressive. And so if you had to look at one measure only, would it be gait speed in terms of a patient being able to tolerate a transplant at an elderly age? Would that be the biggest measure?

Dr. Sorror: I would say yes, gait speed would be one of the very critical tool to assist older patients before any treatment for cancer and specifically for STEM cell transplant. But the comorbidity index comes, almost hand in hand with gait speed because they kind of cover two aspects of health. The co-morbidity index kind of asks the question about what other medical problems the patient has, while the gait speed is kind of assessing the physical performance the physical performance of a patient could be affected by cancer, could be affected by medical problems, could be affected by conditioning, how active the patient is, could be affected by other factors. Sometimes even psychological health could affect the gait speed. So, these two elements, I think the two most important, I'm not undermining the other factors too that we look at, but I would say yes, these two elements are the most important in giving wealth of information about patient health and expectations of treatment.

Host 2: Well, it'd be interesting to look as a Medical Oncologist on whether or not gait speed or the comorbidity index would be useful in solid tumors as well. My presumption is that it would.

Dr. Sorror: I think that's a very good question. And one of the ideas that I had in my mind is how to reach to my colleagues in solid cancer and how to establish the same research that we've been doing in trans, STEM cell transplant for blood cancers to establish the same thing for solid cancer, because I think it would be quite, quite informative, especially now that we have the chimeric antigen receptor therapy or what's called CAR T-cell cellular therapy that's actually offered to not only blood cancer patient, but also patients with solid cancer. And one of the new projects that starting to work on is how to take some of these measures and apply them to this new cellular therapy. What's called CAR T-cell offered to solid cancer and blood cancer, and how to use it in order to inform the physicians and the patients about the expected risks.

Host 2: Well, that'd be fascinating to see how that plays out in the future. What do you see as the most exciting thing on the horizon for you now? Is that the CAR T-cell therapy, in terms of your research, or is there some other, or potentially how immunotherapy affects transplantation these days?

Dr. Sorror: Well, I think immunotherapy and CAR T-cell is a very exciting field because it brings in the idea of potential cure, but maybe with less toxicities than the transplant might cause on the long-term, because the CART-cells are basically come out, the immunotherapy is basically coming from the patient to the patient himself or herself, while the STEM cell transplants for most of the or many of the blood cancer types comes from a different donor and there is a different immune system.

So, I think the CAR T-cell is one of the exciting new area to investigate. And also think about using it in combination with a transplant because sometimes, especially with the patient who has very aggressive cancer, and hasn't responded to many treatments before. One of the ideas is how to use CAR T-cells to help control the disease of the cancer to a level where you can offer the STEM cell transplant as a salvage treatment and between both of them, you might treat, reach your best results. That's from the aspect of novel treatment for cancer. For my research, what's really exciting, to me is I spent good amount of my time as a researcher at the Fred Hutch in trying to understand risks, as I just said earlier, in trying to develop models or test models, to understand which patients have the highest risk when we offer STEM cell transplant. But about a couple of years ago, I actually took this a step further by designing the first of its kind clinical trial that tried to offer interventions to patients who might have a lot of medical problems or might have a slow gait speed, which we call it frailty.

How can we offer interventions that actually make them tolerate the transplant maybe as good as the patients who are healthier. And that trial is funded by the National Institute of Health, the National Cancer Institute. And currently we have six institutions enrolling patients on that trial. And Fred Hutch is the lead center for that trial. And what we're trying to do here is we take every patient who could be 65 years or above, or patients who have multiple medical problems or patients who have slow gait speed and we randomize them, which means we flip a coin and we put them into one of different interventions. One of them is to try to use palliative care before and after transplant as an additional level of support, supportive care to help manage their symptoms, to help manage the difficulties they go through a transplant given that they are high risk patients.

The second intervention, we look at what other medical problems they have. They could have heart disease, for example. And in that case, we work closely with our cardiologists to build a program of exercise, program or for strength training, diet, other details that are specific for these patients with heart disease and the same thing for a patient who might have lung disease, or might have liver disease. We have a specific program for them that's delivered in a form of a booklet and sometimes tapes. So, the patient will take that to where he's staying. And while he's receiving transplant at SCCA will be reading our booklet. Will be doing the exercises. Will be applying the rules about diet that's specific for his health. And our goal of this is make them tolerate transplant better. Make their quality of life better, make them live longer because we make them more resilient to transplant.

Host 2: Wow and that'll be very impressive. It's nice to see a little cross-pollination between the solid tumor world in terms of palliative care, how that helped extend lives with patients with stage four lung cancer and the TML and Tom Lynch study from 2012, I believe. And now that's coming back to or going to the STEM cell world. And it makes perfect sense to me that if you can enhance all these other aspects of a patient's life, that they can manage to get through such a major intervention as a bone marrow transplantation.

Dr. Sorror: Absolutely. I think you really bring up a good point that this has been explored in lung cancer patients before, while they're receiving their chemotherapy and has shown improvement in survival and quality of life. STEM cell transplant is a procedure that put a lot of demands in patients early on. And I think, I do believe that palliative care support eventually could be a part of the standard of care, depending on the results of our trial. I might have missed to say that one arm used palliative care. One arm used the management of medical problems. That third arm, it's a combined arm. We offer palliative care support as well as the management of medical problems. And I think if you do these two things together, you might reach actually the best the best results.

Host 2: Yeah, that's what I would expect as well. It's impressive to me that you've got a total of six centers on this because I think this sounds like a giant study and a lot of effort.

Dr. Sorror: Yes. It's actually required a lot of effort to build these centers together and coordinate that trial. We continue to invite other colleagues to join us. We're still at the beginning of the trial and we might expand the number of centers where we offer this trial. And I think that's also good for the trial because you then get the diversity of different types of patients.

So, when you finish the trial and you come up with a conclusion at the end, you kind of feel confident that conclusion would apply at other centers in the nation, because you had number of centers from different states, from different metropolitan areas, that's makes good representation of different types of patients. So, I'm really excited that my colleagues are enthusiastic about this study and they are opening this trial at their centers. I think it adds a lot to that benefits of the trial at the end.

Host 2: Well, I can tell you that I'm not doing any transplantations, but I'm enthusiastic about the trial as well. I remember what a game changer that you know, the TML Tom Lynch study was in terms of how my colleagues who were in oncology looked at palliative care. I think many people were, well, yeah, we can do this. It's not that big a deal, but I think the realization of how much time that added onto a person's life was that we need professional palliative care experts who were going to be involved and involved quite heavily more than just an oncologist would be.

Dr. Sorror: Absolutely. I think the more supportive care you provide, the better. We actually use a specific model called the Nest 13, which actually we give it to the patient. And it has 13 questions it asks the patient, what is the most pressing problem you have that week? And then we take the patient answer. We give it to the palliative care specialist. So, when the palliative care specialist walks into the room or calls the patient to discuss, then they will really be focusing on the problems that's most pressing to the patient at that week. So, it's really very individualized form of intervention where we're trying to respond to the patient needs and provide the care that could help them go through that process more successfully.

Host 2: Wow. Very impressive. What other sites are actually doing this incredibly important work?

Dr. Sorror: So, we have that trial open at the Oregon Health and Science University in Portland, Stanford University, Mayo Clinic, University of Minnesota and Karmanos center. And those are the current sites that joined the trial and we continue to reach to other collaborators on the East coast and the Midwest to see if others will be interested in joining us. And I would think, I would think by the end of this year, we might shape our trial into maybe up to 10 or 12 centers.

Host 2: Excellent. And in with that in mind, when do you think the readout might be? Two, three, four years from now?

Dr. Sorror: But that's the interesting thing about the design of this trial. We designed it as two phases trial. So, in the first phase, which takes about half of the patient required. So, the trial required about 600 patients to be involved from many number of centers. The first 300 patients is in a phase two study that asks which of the three intervention arms is better than standard of care that we're currently doing.

So, we will know some information halfway through from that phase two that will probably determine one of those interventions is doing better than everything else. And then the phase three, which has another 300, we will ask now a definitive question. That intervention arm that we selected from the phase two, how good it is compared to standard of care? So, after half of the trial, after we enroll half of the patients for the trial, we would get some information that we will publish. And we tell the community that we actually found one of those intervention arms to be suggestively better. And I'm expecting, if you're asking me about timing, I'm expecting sometime next year, in 2022, we might be able to publish these early results. And the definitive answer will be about two years after that where we get the results of the second phase of the trial.

Host 2: Well, that is amazingly fast too. I mean, we are on the cusp then of potentially some game-changing information in transplantation.

Dr. Sorror: Yes, I think so. And then from the aspect there was another trial from that aspect or risk assessment. I'm doing another large trial with the blood and marrow transplant clinical trial network, which is a national network that has 52 centers. We're doing a large trial, I'm the co-chair where we trying to take the comorbidity index that was developed here in the Fred Hutch in 2005 and add the other factors that we found to be important, try to expand it and make it a larger predictive model. So gait speed, for example, as one of the, there are 13 factors that we're adding to the co-morbidity index. Gait speed is one of them. And we call that model the Charm, and we think that the Charm model that probably we will get a results next year, will give older patients any older patients, 65 years or above will, give very definitive information about the risks. So, that's another exciting clinical trial that probably will get some results soon.

Host 2: Yeah, we'll have to have you back on when essentially the phase two data comes out. That'll be interesting.

Dr. Sorror: Yes. And actually next year would be perfect because we will have the observational trial for the new risk model probably published. And then hopefully the phase two of the intervention trial published, there would be two, two good pieces of information to share as an update. It would be really interesting for a lot of older patients.

Host 2: Yeah, and I think this is also important, you know, for people who are referring into SCCA, things are changing a lot in terms of who we can transplant these days. And I think this is all really germane information that sometimes just doesn't trickle down to the docs in the field. So, it's be good to, to do something like this.

Dr. Sorror: Yeah, one of the papers that we're trying to publish, it will actually come out in few days, if you look at the percentage of the patients, for example, with acute myeloid leukemia, getting a transplant and population studies, it's actually than 10%. So, that community physicians are keeping the majority of patients away from transplant, thinking that they cannot tolerate it. So, by the research we're trying to do it, I mean, the publications do address a lot, but not everybody reads these publications. And I think that's where ways of reach, like this could have more impact in delivering the story that there is a lot to learn by referring a patient to a center like this, where they can get a better chance of assessment of the risk. Nowadays we do many of our consults virtually, so it's really not a burden for a patient who does, who lives far away from SCCA to be the first for a consult, and talk to a transplant physician and evaluate the risks and talk about is transplant the treatment for them or not. I think that's why it's, it's actually more than any time, we should ask for at least the patient be seen by a transplant physician in a virtual consult or an in-person consult to understand that transplant is a way for treatment or not.

Host 2: Well, all of this has been and really exciting. I think we're just about out of time and unless you have anything else, Dr. Sorror turn it back to Aimee and she can wrap it up with some information about how to get hold of you in case some physicians or patients who are in the Washington area or outside of that would like to get hold of you.

Dr. Sorror: Well, it's been my pleasure and I'm always happy to provide any feedback to physicians or patients.

Host 1: Thank you so much. Thank you to my cohost, Dr. Lukas, and to Dr. Sorror for joining us today. Such a really insightful conversation and also a lot of promise in this field. So, thank you for sharing so openly and also want to thank our listeners for tuning in to the Oncology Soundbyte, and to hear more and subscribe to the Oncology Soundbyte in your favorite podcast app, and to receive updates on our future podcast episodes along with other news out of SCCA, you can go to Seattlescca.org/providerblog and click subscribe for more news from SCCA. But until next time, thank you for listening and take good care.