In this episode, we sit down with Dr. Joseph Pidala from the Moffitt Cancer Center to discuss chronic graft-versus-host disease (GVHD), a complex condition affecting many stem cell transplant survivors. We focus on the latest prevention strategies, treatment innovations, and the critical role that clinical trials continue to play in advancing care.
We begin with promising news around prevention. Dr. Pidala shares data from the BMT CTN 1703 trial, which compared conventional GVHD prevention to a newer approach using post-transplant cyclophosphamide (PTCy). This newer strategy significantly reduced the incidence of both acute and chronic GVHD, signaling a major step forward in preventing this debilitating condition.
Despite advancements, many patients still experience chronic GVHD, which drives the need for new treatments. We explore several groundbreaking clinical trials that are rethinking traditional steroid-heavy treatment protocols. One study is testing Rezurock (Belumosudil) as a preemptive treatment during early symptoms, while another is investigating whether Jakafi (Ruxolitinib) can be used as a first-line treatment to reduce steroid reliance. These trials challenge old norms and aim to improve long-term outcomes.
We also take a look at the four FDA-approved therapies currently available for steroid-refractory chronic GVHD: Ibrutinib, Jakafi, Rezurock, and the most recent addition, Axatilimab (Niktimvo). These drugs, each with different mechanisms and side effects, give patients and clinicians more flexibility than ever before. We touch on other widely used therapies like ECP (photopheresis), which, while not FDA-approved, remain an important part of care.
Patient involvement is a key theme throughout. Dr. Pidala emphasizes that progress would be impossible without those who enroll in clinical trials, sharing inspiring examples of patients who benefited from early access to now-approved drugs. He encourages patients to advocate for themselves and speak up about symptoms, improvements, or quality of life changes. Patient-reported outcomes are becoming standard in trials, offering critical insight into treatment success from the patient's perspective.
Dr. Pidala also highlights the importance of addressing GVHD holistically. Beyond core treatments, supportive care—including help with dry eyes, itching, joint mobility, pain, and mental health—is crucial to improving day-to-day life. He stresses that long-term recovery is possible and shares a moving story of a young woman with severe GVHD who, through persistent treatment, regained functionality and returned to a fulfilling life.
We close with advice for patients: be proactive, informed, and open to trial participation. And when seeking information on trials, always start by asking your clinical team—they’ll know what’s available and suitable for your specific situation. Above all, Dr. Pidala leaves us with a message of hope—there’s real progress being made, and the future looks brighter than ever.
Thanks to our Season 19 sponsors, Incyte and Sanofi.
00:40 – Introduction to Dr. Joseph Pidala
01:21 – New GVHD Prevention Approaches
02:44 – Why Clinical Trials Matter
03:22 – Challenging Steroid-Based Treatment Norms
06:14 – Timeline for New Treatment Results
07:02 – FDA-Approved Drugs for Chronic GVHD
09:09 – Individualized Treatment Approaches
10:69 – The Role of Patient-Reported Outcomes
13:44 – Symptom Management and Supportive Care
15:20 – Addressing Mental Health in GVHD
17:30 – Inspirational Patient Story
21:12 – Advice for GVHD Patients
23:02 – How to Find Clinical Trials
25:06 – Final Thoughts and Message of Hope
Peggy Burkhard (00:40):
Well, hello everyone. So, today, we have Dr. Joseph Pidala of the Moffitt Cancer Center with us. Dr. Pidala is an expert in chronic graft-versus-host disease, and we are so lucky to have him with us today.
He's going to share information about treatment options, advances these past few years (and wow, have there been a lot), and the importance of clinical trials. We are going to get some great advice and an immense amount of hope today.
Let's get started. Welcome Dr. Pidala.
Dr. Joseph Pidala (01:09):
Thanks so much. It's good to join you.
Peggy Burkhard (01:10):
So, Dr. Pidala, let's talk about the new GVHD prevention approaches that are reducing the burden of chronic graft-versus-hosts disease.
Dr. Joseph Pidala (01:21):
Well, to start, that's one of the more exciting topics that we're going to cover today. There are new GVHD or graft-versus-host disease prevention approaches that are showing major promise. In one of the ways that they're helping is reducing the burden or the proportion of people that are affected by chronic graft-versus-host disease.
And one of those examples was a very large national study run by something called the BMT CTN, it's the National Transplant Cooperative Group that led a marrow transplant clinical trials network. There was a BMT CTN 1703 study that randomized patients to either a conventional GVHD prevention strategy, or one that has promise that is called post-transplant cyclophosphamide or PTCy-based prophylaxis.
And this very large randomized study demonstrated benefit of the PTCy-based approach in optimizing the sort of composite success measure. But one of the ways that group was more successful was less people affected by severe acute GVHD, and also less people affected by chronic graft-versus-host disease.
So, this trial really has been a breakthrough and holds promise to reduce the proportion of people affected by chronic GVHD.
Peggy Burkhard (02:32):
Well, that is just really, really good news, wow. We know clinical trials are making a difference and I love talking about clinical trials. Can you share more about the trials that are going on?
Dr. Joseph Pidala (02:44):
Absolutely. I think certainly, there's a lot of hope based on these new prevention approaches, so reducing the proportion of people that are affected by chronic GVHD. But what we know is that that approach and others really are not perfect. So, even with our current best prevention approaches, there still are people affected by chronic GVHD for sure.
So, as that remains true, really, we need innovation in novel treatment strategies. So, delivering treatment to people who are affected by chronic GVHD. And there are several things going on in the field that are very exciting, maybe I could share a few of those with you.
Peggy Burkhard (03:20):
Yes, please share with us.
Dr. Joseph Pidala (03:22):
Just as a couple of examples, there are a couple of trials going on right now that are really challenging some longstanding paradigms or kind of longstanding expectations about how we need to treat chronic GVHD.
And that longstanding paradigm is people develop highly symptomatic chronic GVHD, we start them on a high dose of prednisone, which is a steroid, and we give them a very prolonged course of steroids.
And that's been a longstanding standard mostly because there have been several clinical trials before that have challenged that assumption and have not made a major breakthrough. So, in other words, that treatment remains the standard of care.
However, it's really an imperfect standard, and the reason is that it's the minority of people that will have long-term success, long-term resolution of their chronic GVHD with that treatment, and also being on long-term steroids can produce its own set of problems, side effects.
So, with that being the existing standard and an imperfect standard, there are new trials that are really challenging that paradigm. And as a couple of examples, one is a trial that's going on that is testing something called preemptive therapy.
And what that basically means is trying to intervene at a very early time point when people are minimally symptomatic from chronic GVHD to see whether that early intervention can spare the long-term need for additional chronic GVHD treatments.
And that study is actually testing a drug called Rezurock or Belumosudil that's already FDA approved for treatment of advanced chronic GVHD. But it's testing that drug in this early setting compared to a placebo intervention to see does that make a meaningful difference.
So, basic concept there is very early intervention, does it change the natural history or the way that chronic GVHD behaves? And the main goal would be to try to prevent long-term symptoms and long-term need for treatment. So, that's one major study that is really kind of challenging, normal treating paradigms.
The other one I want to mention is also directly challenging usual paradigms in the sense that it's using a drug called Jakafi or Ruxolitinib and treating people at the point where we normally intervene with initial therapy either with that drug or prednisone.
So, it's randomizing people to one or the other of those regimens. Then the basic idea is can that drug, Jakafi, which is already approved again for more advanced chronic GVHD, can it be used in a first line setting and spare people exposure to steroids?
So, these are kind of two examples. There are several others where there are new trials that are trying to kind of push onto the board, innovate in the space of therapy of chronic graft-versus-host disease, and the hope is that these may show some promise and actually improve patient outcomes.
Peggy Burkhard (06:07):
Well, this is just great news. And how long will it take for these studies to come to fruition?
Dr. Joseph Pidala (06:14):
They will require a little bit of time. These two studies I'm sharing as examples are active, they're actively underway in enrolling patients. So, actually, I think certainly not right away, more on the order of like a couple of years from now. But I share these just as examples of the concept that researchers are really trying to kind of bring new solutions to this longstanding problem of chronic GVHD.
Peggy Burkhard (06:36):
Great. I know in the last seven years, there have been so many new drugs, and we all know that the new treatments are a result of clinical trials, the FDA approvals.
So, Dr. Pidala, can you share just some more of the excitement of that? I just think of the people that got into these trials and the difference they're going to make for future survivors. I just would love for you to talk more about that if you can.
Dr. Joseph Pidala (07:02):
Absolutely. That's another point of hope and promise is that we're kind of living in a time where there are multiple FDA approved drugs for advanced chronic GVHD treatment or what is called steroid refractory chronic GVHD treatment.
That term just means that people have developed chronic GVHD, they've been treated with steroids, and they continue to have GVHD symptoms. And as of right now there, there are actually four FDA approved drugs for this indication.
These are Ibrutinib, it's also called Imbruvica; Ruxolitinib, which is also called Jakafi; and then there's Belumosudil, which is also called Rezurock. And then actually most recently, a drug called Axatilimab or Niktimvo.
So, these are four treatments that are now FDA approved for advanced chronic GVHD treatment that as you said, it kind of came to that milestone by the way of success in clinical trials. So, patients were treated successfully in clinical trials, and that evidence of it helping people and being safe led to their approval.
And so, now, we're in a time where we can employ all four of those options as well as others in the treatment of people with chronic GVHD. And it's pretty noteworthy because it gives us a lot of options, gives patients a number of options, and also, these drugs are different. They act differently and they have different side effect profiles and some different kind of logistical burden associated in each one of them.
For example, some are pills, some are IV therapies, and so there really are a range of options based on the patient's individual needs and their out-treatment history. I should say that actually, there are several other commonly used chronic GVHD treatments that don't have the same status, like the same FDA approval. One good example of that is something called ECP or photopheresis. This is a therapy that we use on a regular basis.
And so, really it all kind of illustrates that there are multiple options for patients and I think that really does provide hope because it's relatively common that patients kind of don't achieve the outcome that we all want with a single therapy.
In other words, sometimes their symptoms are not adequately controlled, and we need to kind of move on or pivot to a next treatment. So, having this range of opportunities for sure even really gets patients and also clinicians a reason to be optimistic.
Peggy Burkhard (09:09):
Oh, it really is such an exciting time, and what I'm hearing is that there really is not a one size fits all, but isn't it nice to have options as a doctor treating these patients whereas just eight, nine years ago, I can't imagine how difficult it was compared to today.
I love working in this field, and I love seeing the excitement and the passion of this very small population of physicians and patients experiencing this, it is really something to see. There are others on the horizon because there are always clinical trials going on. Is that true Dr. Pidala?
Dr. Joseph Pidala (09:47):
It is true. I think it's important to realize that clinical trials in those advances that we're seeing in the field would never be possible without patients that are very generous with their time, and volunteering to take part in these clinical trials, so patients are really integral to the success of us making advances in the field.
As an example, I've had multiple patients myself that actually took part in some of those clinical trials that led to those FDA approvals. I've even had patients who had a therapy on a clinical trial and then actually after the approval, continue that same therapy as a standard of care and continue to be very successful several years later.
So, just wanted to highlight that patients are really central to our ability to conduct clinical trials and also, advance the field and ultimately, improve the outcomes of future patients.
But as you mentioned, we still don't have perfect solutions, and there's definitely a lot of need to continue innovating. And yes, that is very true, there are a number of clinical trials that are active and ongoing, so that holds a lot of additional promise.
Peggy Burkhard (10:45):
I couldn't agree with you more. The heroes are the patients that are willing to take the time to partake in a study to make a difference, and we really want to do a shout out to them.
So, Dr. Pidala, it seems that the focus on the patient's perspective in chronic graft-versus-host disease continues to grow. Can you tell us more about the patient reported outcome measures?
Dr. Joseph Pidala (11:09):
Definitely. So, just like we were saying, patients are central to be able to make progress through clinical trials. Patients are also central to everything that we're doing in the clinic despite the provider or the clinician having important insights into how to treat the patients, how to help them to make progress.
It's also true that no one knows better what it's like to live through chronic GVHD other than the patient themselves. Patients really have valuable insights into their own care and also have a keen awareness of their own benefit and side effects from treatment.
So, PROs are Patient-Reported Outcomes. These are outcome measures that capture the patient's experience, whether it be their symptom burden, meaning how chronic GVHD is affecting them through their symptoms. The other is, for example, patients reporting their own sense of their quality of life.
The thing I wanted to point out is that if patients have this keen awareness of their own sense of how they're doing with their treatments, increasingly these PROs or Patient-Reported Outcomes are really being elevated in a way of seeing them as a significant component of judging the success of treatments.
For example, there's several patient-reported outcome measures where PROs that have been routinely employed in these major clinical trials that we were discussing earlier. So, kind of capturing another dimension of clinical benefit by way of patient reported outcomes that this is becoming really a very standard component of clinical trials.
And the other thing I just wanted to point out is that there is some kind of newer research on something called patient reported response. In addition to us kind of calculating a patient's response to treatment based on certain NIH response criteria or using the clinician assessment of a response, these are tools that we normally use to assess someone's response to treatment.
There's been some new research on capturing the patient's own sense of their response to treatment, meaning do they feel like they're getting better or not on a treatment? And that research seems to indicate that the patient's perception of their own benefit is valuable, and it may be capturing a dimension of their clinical benefit that may not be fully captured by those other response tools.
Peggy Burkhard (13:16):
Wow.
Dr. Joseph Pidala (13:17):
Really, it's kind of bringing the focus in a new way on kind of the critical perspective of the patient themselves.
Peggy Burkhard (13:23):
It's almost like they're listening more to the patient and taking that more into account. That is really neat. I would imagine they're going to see great results from that. Thank you for telling us about that.
So, you treat graft-versus-host disease patients at Moffitt. What really are the most common issues that you treat, Dr. Pidala?
Dr. Joseph Pidala (13:44):
Well, I treat people with chronic graft-versus-host disease, and all of the things we just discussed are completely relevant to our day-to-day practice. Meaning using those available therapies, patients commonly needing several lines of therapy, helping patients to get through this experience. I think one other kind of key thing that we do on a regular basis is also in addition to treating their underlying GVHD, also important to manage the symptoms that are a consequence of the GVHD.
There are a number of things that we do outside of a core GVHD treatments to help them to really kind of optimize their quality of life, and kind of live their best life that is possible while they're dealing with this problem. So, there are a number of what we call supportive care measures or ancillary measures that we use to really cool off or deal with those problematic symptoms.
For example, helping people to manage very severe dry eyes, or helping people to manage bothersome itching or skin dryness or helping people with functional limitations from GVHD, like severe skin tightening or severe joint impairments by way of both the treatment, but then also supporting them through kind of targeted interventions by way of physical therapy-based interventions.
Not to mention some people have significant pain that they need help with, also many people struggle with other additional issues that go along in this journey. For example, mental health related concerns, and so kind of thinking about that whole spectrum in addition to treating their chronic GVHD, we need to think about them holistically and think about how do we optimally manage these bothersome symptoms to help them achieve the best quality of life that is possible.
Peggy Burkhard (15:20):
Dr. Pidala, I'm so happy that you mentioned the mental health aspect because you know at the LINK, that is a lot of our job. We are helping people just try to live their best life, they worked so hard to stay alive, and now, they've got this rare disease, and we offer so many programs as you know, just really aimed at their quality of life and their mental health.
And I think it's so important to mention that it's okay to need to talk to somebody about this. This is really tough stuff, and I'm sure your center does a really good job holistically like you said, to take care of the many aspects of GVHD. It's not just physical ailments and pain, it's everything.
And I get to see the patients who make it, who get through it, it burns out somewhat, and I know I'm preaching to the choir because this is what you do for a living. So, it's really exciting to see what happens a few years after transplant. Sometimes it gets worse for a while, but a lot of times, we see things getting better for people.
Dr. Joseph Pidala (16:22):
That's one thing I would definitely highlight because a lot of what we've discussed here today is future oriented and reasons to be optimistic, and sort of like thinking to kind of forecasting a good outcome, a better quality of life kind of moving forward. And I think something we try to encourage our patients to do as well along their journey, they also, genuinely I would share about in many ways, there's reason to believe that.
And actually, if I think about the patients in my clinic, certainly there's some people that are really struggling with chronic GVHD issues, but there're an equal share of people who have made it through that, and are long-term survivors, have no or minimal GVHD, are on no or minimal immune suppressive medications, returning to work, living their lives, being with their family. So, I think, in many ways there are reasons to be optimistic.
Peggy Burkhard (17:10):
Yes, more than ever it is an exciting time in this field. So, Dr. Pidala, one of my favorite parts of doing these interviews is asking the clinicians for an anonymous favorite story. Maybe a patient that really touched your heart, they were really maybe struggling. Do you have a story for us today?
Dr. Joseph Pidala (17:30):
I do, and to be honest, thinking about the question, there's so many stories. I've had the good fortune of taking care of a lot of patients and a lot of patients with chronic GVHD, and I have to say it always really inspires and impresses me to see how resilient they are, and how hopeful they are, how much they are willing to kind of go through some difficult times and kind of look forward to a better future, so it's really very inspiring in a lot of ways. I'm not sure I can name the most memorable case because there's so many.
To be honest, one of the really nice things about the work that we do is the continuity, building relationships with our patients and their families and kind of caring for them over a long period of time, I have to say that's one of the most meaningful aspects of what we do.
But if I had to pick one (laughs) example, I would say, again, speaking anonymously, one young woman comes to mind who really had a very challenging time because she had two of some of the most difficult to treat types of chronic GVHD.
Chronic GVHD can affect your body in a lot of different ways. Some of those ways are recognized as kind of subgroups or kind of like types of chronic GVHD, and she unfortunately had both of them. One of them is something that we call, like the medical term is called cutaneous sclerosis. Sometimes, people just call that sclerotic GVHD, sometimes people say it's just an issue of like hard and tight skin. It's that problem.
People have varying degrees of hard and tight and not movable and not pinchable skin, and sometimes it can be problematic to the extent that people can't move their joints very well. So, people can be very rigid and very stiff. So, she had that in a very extreme way.
And also, she had this other problem that is called BOS or bronchiolitis obliterans syndrome which again is a medical term, but what it really means is just GVHD affecting your lungs and making it difficult for you to breathe, and also making it difficult for you to tolerate normal activities because you feel so winded and short of breath all the time.
So, these two things are kind of some of the more challenging kind of concerning versions of GVHD, and she unfortunately had both and has both. The thing that's really memorable and really inspiring is that number one, I mean she was very determined to get better and she is.
In a lot of respect, I've been seeing her back in clinic many times, and she's had major objective improvements in the tightness of her skin, her ability to move, her ability to function, and also over time, monitoring her lung function by breathing tests or pulmonary function tests. She's made measurable improvements and actually alongside of that, is able to do more.
As I mentioned, she's a young woman, she actively works, she has a family, so she has to climb up a couple of flights of stairs to get to her home, and so it's like there are all these ways that this was a major challenge for her.
But with effective treatment, she's come such a long way, and while not totally normal yet has made such a great improvement that it's very clear that she’s kind of getting their life back. So, all these issues and impairments and problems from the GVHD are over time getting better.
So, it's really inspiring to see that, and also really kind of illustrates that there's a lot of reason to be hopeful even amongst those people who have really challenging versions of chronic GVHD. There's reason to be optimistic that with time and with treatment, you can make major strides.
Peggy Burkhard (20:47):
Yes. And those are two of the tougher ones. And to hear that she's a young woman with a family and all this help, I may need to talk to her to be a mentor for us. These are exactly the kind of people that just give others so much hope, and just keep on keeping on. She's got a lot to live for, and I love to hear stories like that, so thank you so much.
Is there anything else that you would like to cover today, Dr. Pidala?
Dr. Joseph Pidala (21:12):
A couple of things. One is everything I shared today's really coming from my perspective as a physician, but also is very much informed by my partnership with my patients on a day-to-day basis in terms of treating them, helping them, looking to them for their perspective, all of those things.
So, I think from that experience, one of the main things I would recommend to patients is be your own best advocate, you are definitely an equal partner in this. Your physician and your team, they have the medical knowledge and they want to help you, but at the same time, you're central to the process.
So, in all the ways we discuss, really advocate for yourself, let your team know how you're feeling, let them know whether you think you're improving or not on your treatment, let them know what kind of bothersome symptoms you need help with. In other words, when you come to your clinic visits, you're one central piece of this process, so really feel empowered by that and be your own best advocate.
And then the other thing I would share is a lot of what we talked about here today is about the advances we've made through clinical trials historically, and also the promise of ongoing clinical trials to kind of shape the future, to help people in the future.
And so, whenever there are clinical trial opportunities that you can consider, I would just say please give it some consideration because it's through the kind of willingness and the generosity of patients to take part in clinical trials that we actually continue to make progress.
Clearly, clinical trials are always elective or optional, but your job as a patient is to kind of hear about them as an opportunity and to learn about them deeply, and then make an informed position about whether or not something that you would really consider or not, it is never a mandatory thing.
However, if you heard about a trial opportunity and it made sense to you and you reviewed the details that we felt like was the right choice for you, I would just say please keep an open mind about that because truly, it's very helpful for everybody involved, including potentially yourself, but also, patients in the future for sure.
Peggy Burkhard (23:02):
Absolutely. And what is the best reliable source for clinical trials? Where do we steer people?
Dr. Joseph Pidala (23:09):
That actually I think is a really good question because there are multiple different ways you can find out about them, and to be honest, sometimes it can be confusing or overwhelming or just not very effective. You can kind of do a lot of searching and kind of not find what you need. And I think part of that issue is that not every clinical trial is open at every transplant center or every hospital, or every clinic.
And so, I think probably the people that will know best what are the active open clinical trials at any given moment are your actual clinical team, meaning your doctor and your clinical team at your clinic or your hospital or cancer center. Really, I would look to that and just ask them directly, specifically, like, “For my current challenges, what are the open clinical trials that I could take part in and can you give me more information about them?”
They really should know best, what is possible at that moment, at that center, and or they could tell you something about what is projected to be open in the future. Because one of the things about clinical trials is that they are dynamic. They start, they enroll, they finish, and then it's no longer an opportunity. But the thing is, and then there's the next trial.
So, asking your doctor directly about, “Can you forecast for me what's open now and what's going to be open in the future, and how does that align with my own timeline? Like by the time that I need something like that, what are we going to consider?” Again, I think that's something that your individual doctor can really help you with.
In other words, I think that really should be the source of truth. There are a bunch of other ways that you can search online, but I think it may not be as accurate or timely or efficient as just directly asking your doctor.
Peggy Burkhard (24:38):
Sounds good. This has been terrific. Thank you so much for everything today, for being with us. I can imagine your patients just love you. You are so warm and approachable, and I just so appreciate everything you said today. Thank you.
Dr. Joseph Pidala (24:55):
Absolutely. It was really a pleasure to connect with you, and also, I think that one of the big themes of everything we talked about today, it's just there's promise and a lot of reason for optimism, and so I would really treat that as a take home message from this discussion.
Peggy Burkhard (25:06):
Well, thank you.