S2 Episode 2: Quality of Life After Transplant and CAR Therapy

2 days ago 8

This transcript has been edited for clarity. For more episodes, download the Medscape app or subscribe to the podcast on Apple Podcasts, Spotify, or your preferred podcast provider.

Ann H. Partridge, MD, MPH: Hello. I'm Dr Ann Partridge. Welcome to season 2 of the Medscape InDiscussion podcast series on cancer survivorship. Today, we'll discuss chimeric antigen receptor (CAR) T-cell therapy and transplant. But first, let me introduce my guest, Dr Stephanie Lee. Dr Lee, who is also an old friend and a mentor of mine, is a professor at Fred Hutchinson Cancer Center and the University of Washington in Seattle.

She's a hematologist and a blood and marrow transplant physician-scientist who treats patients with lymphoma, leukemia, and other blood diseases who have had allogeneic stem cell transplants. Her research aims to improve the lives of bone marrow and blood stem cell transplant recipients. She really is a maven in the field for studying quality of life in this group of patients. Welcome to Medscape InDiscussion Cancer Survivorship podcast. Thank you so much for being here.

Stephanie Lee, MD, MPH: Thank you for inviting me, Ann. I am looking forward to this.

Partridge: I have been looking forward to this discussion. One of the things I like to ask my guests on this podcast is what got you interested, not just in the field of stem cell and now CAR T-cell procedures but studying the quality of life of these patients. How did you get there in your career?

Lee: That's a great question. How does anyone end up in their research niche? I got involved in patient quality of life because I really felt the patient experience was perhaps lacking from what we were doing. I knew I was interested in transplant. I knew I was interested in survivorship and some of the other complications of transplant. Not a lot was going on within the stem cell transplant field in terms of looking at patient quality of life and actually measuring that and understanding how that affects the patient experience also how we determine if our treatment is successful. I think part of that was because we were very focused on just getting people through this really rigorous process. We knew that there was going to be a lot of symptoms, a lot of hits to quality of life, but we sort of justified it because this intensive treatment would cure patients. But there was room to think about other potentially important things at end points. Patient quality of life was also being looked at in other fields, just not in ours. Quality of life has always been something that I think is really important. Many will say that survival is the most important thing. When you get into the survivorship period, that's when you face a lot of these complications. If you don't think about quality of life, you're not thinking about how to make it better, how to prevent it, how to mitigate problems. I just saw a lot of suffering that I thought needed to be addressed.

Partridge: And you have! Let's dig right in. What kinds of long-term medical issues are we talking about? We can talk about medium-term and long-term issues these patients face from transplant and now, into the ever-evolving CAR T-cell treatments.

Lee: I think the spectrum of what they face is very different for those different kinds of transplants and from CAR T cell. What is universal with all of those procedures is that they're usually applied to people who have blood diseases and blood cancers. There's a lot of chemotherapy that's given beforehand, which has its own spectrum of late effects. They usually will get chemotherapy of different intensities at the time of the procedure, and then for patients who have allogeneic procedures where they get stem cells from the other donor types, they can have graft versus host disease, which can go on and on and on and have many complications. What is not affected in these survivors? They have risks for subsequent malignant neoplasms and risks for infections. We know that risks for cardiovascular or pulmonary organ toxicity is increased. Fertility can be affected as well as endocrinology, diabetes, thyroid failure, and the list goes on and on. For all survivors, there's this persistent, potential psychological burden from having the treatment, having had the disease, from fear of relapse, so that's another potential late complication that we have to think about.

Partridge: It's essentially all the medical care that these patients can need as either a complication of the cancer, the cancer treatments, or just having whatever comorbidities they brought to the table to begin with. How do you think about this in terms of preparing patients from the beginning for not the transplant itself but for the survivorship phase? When should that start?

Lee: It's sort of a philosophical question because a lot of these patients are right in the midst of worrying about just plain old surviving. The question is when do you bring up these survivorship issues or these quality-of-life issues? My personal belief is that you have to start as part of the whole decision-making process to undergo these procedures, and I don't think you have to go into excruciating detail because honestly, a lot of our patients are focused just on the procedure right ahead of them. But when you talk to survivors, many of them are somewhat bitter and feel like they were not informed because they were not properly educated at the beginning. At least opening that door and trying to assess how much they want to know and are ready to hear from the very beginning is useful. From then on, it's an ongoing conversation at each phase. I think it's important to bring it up, particularly if they need to be involved in something, and they actually need to participate in it vs just knowing that it's a potential risk. Our goal is to cure their disease, and if we're successful doing that, then the rest of their lives they have to think about these late effects and these survivorship issues. We probably pay most attention to it once the acute toxicity of the transplant is over, though, because I think that's when our patients are shifting their attention to [the question of] what's going to happen now? What is the rest of my life going to be like? And they can focus a little more.

Partridge: That is so salient. At Dana-Farber, we try to navigate patients into a survivorship visit at 1 year from the transplant, at least for the allogeneic patients. Patients really just can't handle it at the very beginning because they're just trying to manage the very acute toxicities and when to call us with a fever and things like that. It's not just a philosophical dilemma. How much can a person bear and what will they respond to? There's too much information in too many different directions.

Lee: But there is always the person post-transplant who will say, they never told me that this was a possibility. For those people, I think at least bringing it up is really important. Again, they're not going to necessarily pay attention to the details, but they do have to know that what they're about to undergo has some significant long-term potential complications.

Partridge: Who takes care of all these survivors? How do we care for all of these survivors? What resources do we have for them? That's a lot of questions. How about start with the who.

Lee: This is a big debate in the country because it's a good problem to have, right? More survivors is always a great problem to have, but who has the expertise to take care of these patients? Who has the time to take care of them? For someone who's had a history of a significant cancer, a significant treatment is not going to be your standard internal medicine–type patient where you can really see them necessarily within 15 minutes. I think that's been a big debate in the survivorship field, whether it should continue to be the sub–sub specialists like the transplanter. Should it be the oncologist or should it be the primary care physician? Should it be in a multidisciplinary survivorship clinic? Or do we have to recognize that our survivors are all over the country? We really need to have telehealth outreach vs more centralized clinics.

I think all of these models can work and probably the solution differs a lot for different types of survivors in different financial situations, considering what resources people have and what expertise they have. I think the important thing is making sure that we do whatever we can to make sure that the survivorship stuff that needs to be done gets done by whoever is taking care of the patient, and that's a significant challenge. Even at Fred Hutchinson, where we do try to see the patients at 1 year and get things going so we can make recommendations, a lot of time, they go back into the community and those recommendations can't be followed or won't be followed. Here at Fred Hutchinson, we have a primary consultative mode. We don't often take over their care entirely because we just don't have the staff to be able to do that. We will see people who have active medical problems every 3 months and try to give guidance, but a lot of people are too far away and can't do that. If their financial situation doesn't work for them to come back, then we try to work with their local providers.

Partridge: It's very complicated. This is where guidelines, good communication, that old treatment summary and survivorship care plan could in theory be helpful as a document to kind of pave the way, even though there's lots of controversy and uptake has been challenging. We've tried to do that at Dana-Farber, but it is challenging. What kinds of resources are there for anybody listening who is seeing these patients in their practice? Maybe the communication isn't as perfect as it could be with their treating transplanter, What kinds of resources do you recommend that a clinician or patient reach for? What do you send patients home with or refer them to for their own information?

Lee: There are plenty of materials out there. For patients, you mentioned the survivorship care plan, which to us, is a little more of a solid tumor concept, but we also have that with the transplant where we try to have guidelines. A lot of the patient advocacy groups have different materials where patients can understand the general landscape of when they're supposed to have different tests. For a patient who is really their own advocate involved in their care, there's a lot of guidance for them to be able to work with their physician. We have to acknowledge that a lot of patients just don't have that interest or ability to be their equal partner with their physician, which makes it a little difficult. On the provider side, we have a long document about the kinds of procedures and policies that we follow in terms of testing our survivors and then what to do with that information. When do you intervene? When do you start different therapies? But it's a lot, and this is where I think that gap is. There are people who write the guidelines and who see these patients all the time and think about it a lot. Then there are clinicians out there who may not have that many of this kind of patient and they're not going to be able to go to that document and read it.

They really need or want a little bit more prescriptive information. That's where we try to provide that, for example, "Please do the dual-energy X-ray absorptiometry in this year" or "Please measure the lipid panel this frequently." Maybe with our new IT tools and everybody getting a little bit more savvy about, and having access to electronic things, there could be newer solutions that we didn't have access to in the past that could make sure that people get the follow-up they need.

I don't think it's such an issue at 1 year or even 2 or 3 years. I think the problem is when people get a little bit farther out when that sort of experience has faded a little bit, they may not be seeing their oncologist as much or their transplant physician. Then they're kind of out there in the more general population, and I think it would be great if we can train people, but we just have to acknowledge even though there's more survivors it's not like it's a huge part of someone's practice that they're going to be able to necessarily access that information and do it without some guidance.

Partridge: When the hugs and all the casseroles go away, people are more likely to fall through the cracks, right? The first couple of years, everybody's all-hands-on-deck, worried about the acute-ish complications. But later is when the long-term late things can happen, and if you're not aware, you may either have an untimely diagnosis of something, not do something you could have done to prevent it, or have led to additional morbidity, which is, I think, the challenge. What are you doing and what is going on in the ecosystem in terms of research to improve survivorship care or at least your understanding of the ramifications? I'm particularly interested in the CAR T-cell treatments because it's so new, right? What are their issues and who is studying this?

Lee: In some ways, I think we're seeing a recapitulation of this in the CAR T-cell field in the sense that it's sort of this newer approach. They have these very acute toxicities. Everyone is focused on getting the patients through it. Perhaps not as many people are as attentive to the survivorship phase. Patients get chemotherapy, they had a disease, then they often are very immunosuppressed because we have therapies that are targeted at B cells, plasma cells, and so they don't have immunoglobulin levels. One thing that is a little different, though, is the requirements that they have to be followed up for many years. That has some built-in survivorship monitoring, whereas transplant did not. I think people will take advantage of that. But there are still relatively few papers about the survivorship needs of people after CAR T-cell therapies. You mentioned medium- and longer-term survivorship. We have a lot of people who are sort of in that medium-term. But remember, CAR T-cell is a new therapy, right? We don't have people who are 20 years out. We have people who are 10 years out for the most part. We may not be seeing some of those later toxicities. I think there's an opportunity within CAR T-cell to not wait as long and to know that this is an issue and build it up. Clinicians are starting to follow their patients more carefully and look at not just what is required for post–CAR T-cell therapy, but what's required for follow-up of their disease and the chemotherapy and everything else? I think a lot of research is going on. Clearly, people are paying more attention to survivorship. I think there is a greater effort to think at the time of the treatment about what you could do to prevent some of these complications.

It used to be all about short-term survival and short-term complications. You're seeing the trials be powered now for 2-year follow-up, something that includes more of the survivorship period. There's some work going on about the best way to monitor people and how frequently to do things. Some of the stuff we talked about, like who should be monitoring them, what percentage of monitoring is being done. If the monitoring is not being done, how can we increase that? Of course, there's always the mitigation. If you actually experience a late complication or problem, how is best to treat that? One of the problems is that the survivors are pretty spread out. We know a lot of, what the risk factors are epidemiologically, but actually trying to study that is very challenging. We know cardiovascular risk is higher, but actually studying that in our survivors, getting them all together, they're so heterogeneous. How do you do those studies? That's been a little bit difficult.

Partridge: It's so hard. You're making me think about it. These people, often, are contributing to research by participating in research studies as part of their treatment. You also want them to participate in long-term follow-up or cohort studies, so we can learn and continue to learn from them. Their lives have been completely disrupted from the cancer and all the treatment they've needed for whichever one it is — leukemia, lymphoma; CARs are treating almost everything. I hope it is used for solid tumors soon. The question is, how do we engage a diverse pool of patients? People who come from more diverse backgrounds, especially if they have hits from social determinants of health. How do we help make sure that our research is representative here? We can't do it in the clinical trials, how are we going to do it in the survivorship space? Do you have thoughts on that?

Lee: Exactly what you've said. The first thing is thinking about it and having the will to try to make sure that we include people and that our results are generalizable. There's that general movement and recognition in the country, which I think is also going trickle down and help with survivorship. But we do have some unique challenges. Patients are not coming to the cancer center every week or every month. How do you do this in a more disaggregated kind of way? COVID was horrible in so many ways, but it actually might have helped clinical trials a little bit because we started realizing that maybe patients don't always have to see us, that maybe outside labs are okay, that maybe telehealth is okay. Maybe you can ship medications to people. I would love to see more of that active in the survivorship space so that we can enroll someone who has to work full-time, who has a lot of parental responsibilities, who has to travel from far away in a study of survivorship issues or for any other clinical trial.

I think there's some opportunity with just how we do the trials. There's also opportunities with telehealth, which we weren't doing very much with before COVID, and now, it's a pretty acceptable way to do things. That also might help with survivorship studies because our patients are all over the place. So maybe there will be some of those infrastructure kinds of changes. Just as with acute care, with cancer care, with time to diagnosis, with everything else, we recognize that in survivorship care, there can be huge disparities and health equity issues. I am so glad to see that that is also being considered our research.

Partridge: What you are working on or what excites you the most in the research in this area. Where do you think the next frontiers are?

Lee: I mentioned that in my own personal research, I studied late effects of transplant. We're getting better. We're seeing less of that, but there's still some patients who are really affected by it. That is my own personal focus of research. But we also, for example, every year survey our survivors. Believe it or not, we have people who are more than 50 years post-transplant. We have people who are 10 years post-CAR. We survey them every year to try to find out what the issues are. There's lots of opportunities there. We started off this conversation thinking about quality of life and patient-reported outcomes. That has always been a real focus of my research: to try to get people to understand why that's important and to figure out better ways of measuring it, then hopefully, actually incorporating that into our studies from the get-go so that we understand what the total summation of our treatment on patients is. I think we're making a lot of progress in that, but I would say that on a broader scale, that is one of the things that I'm very interested in doing, which is making quality of life almost a co-primary endpoint. It's not just survival. If you look at FDA parlance, it's length of life and it's quality of life. and so just having the tools to be able to incorporate that into how we judge success I think would be a real accomplishment.

Partridge: You certainly have led the way for that movement, and I am just proud to know you. Today we've talked to Dr Stephanie Lee about quality of life and patient-reported outcomes and survivorship after bone marrow transplant or blood marrow transplant and CAR T-cell therapy. Very exciting times. Survivorship is kind of the gift that keeps on giving in a positive way for researchers because we can continue to learn from the more survivors we have and the newer therapies that create more survivors. Thank you for tuning in. Please take a moment to download the Medscape app to listen and subscribe to this podcast series on cancer survivorship. This is Dr Ann Partridge for the Medscape InDiscussion Cancer Survivorship podcast.

Listen to additional seasons of this podcast.