Listen to this podcast with Dr. Carla Casulo and Judith Trotman to hear about some of the most exciting advancements for follicular lymphoma from the 2024 ASH Conference.

 

ASH News Articles:

What is ASH? https://healthtree.org/follicular-lymphoma/community/articles/what-is-the-ash-conference-dlbcl

FL Specialist Insights https://healthtree.org/follicular-lymphoma/community/articles/ash-24-fl-specialists-insights-new-treatments

Best of ASH 2024: https://healthtree.org/follicular-lymphoma/community/articles/ash-24-the-best-of-it-all

 

ASH Videos: 

https://healthtree.org/blood-cancer/university/courses/klLCY3gkYKWHQDry3bkZ

 

Let me know your thoughts on today's episode! Feel free to email me with questions, comments, or insights at hannah@healthtree.org. 

Hannah Loosle (00:12)
Hi everyone, welcome to today's episode of the Health Tree Podcast for Follicular Lymphoma, where we connect patients with lymphoma to the research and information they need to know about.

If you've been with us before, welcome back. If this is your first time joining us, welcome. We're so happy to have you join our follicular lymphoma community. My name is Hannah Loosle. I'm your host and, the lymphoma education manager here at Health Tree Foundation.

The goal of this podcast is to make research and new information coming out about your disease easy to understand and easily accessible. If you've ever found yourself overwhelmed by clinicaltrial.gov or a medical abstract, we are here to change that. Stick around until the end of the episode when I'll be back to share my final thoughts on today's interview, as well as some additional resources you can dive into related to today's topic.

The topic of today's podcast is follicular lymphoma progress in 2024, where we will be discussing what happened at the 2024 American Society of Hematology or ASH conference.

We are joined by Dr. Carla Casulo and Professor Judith Trotman, who presented during a Follicular Lymphoma Educational Session at ASH. Before we bring them on, I want to give you all a little introduction. Dr. Carla Casulo is an Associate Professor of Medicine and Assistant Director of Cancer Research Training and Education at the Wilmot Cancer Institute.

Dr. Casulo is an international expert and clinician researcher in all forms of lymphoma, best known for her pivotal work in follicular lymphoma.

Judith Trotman is a senior staff specialist and director of the clinical research unit in the hematology department at Concord Repatriation General Hospital in Sydney, Australia.

Professor Trotman and her colleagues have built one of the largest clinical research units in Australia for collaboration and a broad portfolio of hematological trials. I chose Dr. Casulo, Professor Trotman, and the topic for today's episode because it is so important to keep patients like you up to date on the latest and most exciting research in follicular lymphoma. I am thrilled to have them here to share their ASH Insights with you. So now, without further ado, let's bring on Dr. Casulo and Professor Trotman.

Hannah (02:12)
welcome Dr. Casulo and Professor Trotman. Thank you so much for joining us today. I'm really excited to jump into our discussion today. And I first wanna start with an overview of what the ASH Conference even is. So Professor Trotman, if you could start and just give us an overview of what the ASH Conference is.

Judith Trotman (02:31)
the ASH conference is, I guess, the meeting of minds of all the clinicians, clinician researchers, scientists across the world. It really is the preeminent hematology congress every year, where they provide education, but also provide

the latest research data, whether it be basic biological sciences research or clinical trials data, updating the vast breadth of both benign non-malignant hematology and also blood cancer related research. And it's attended by probably, I guess, over 30,000, wouldn't it be Carla? And many thousands of abstracts.

Carla Casulo (03:18)
Yes.

Judith Trotman (03:21)
research data are presented at this meeting. So it really is the preeminent hematology meeting globally that we all look forward to and we're all packed in like sardines into numerous, numerous halls and meeting rooms to hear others ideas and share ideas. It's also a great venue for meeting your peers around the world and discussing your clinical research proposals and trials, how they're going.

Hannah (03:50)
Definitely. Thank you for that overview.

And Dr. Casulo, can you tell us why this matters for patients?

Carla Casulo (03:58)
Definitely. So the ASH meeting, as Dr. Trotman said, is this preeminent meeting where over 30,000 people come from all over the world, but it's also accessible to patients. And so when research is presented at this meeting, it can sometimes change the way we practice medicine. It gives us the opportunity to learn about new treatments that are available for a variety of different diseases. There are sometimes guidelines that come out of the ASH meeting.

and ways of bringing science to the community that comes out of these meetings. So it's a way for us to learn what are the most recent standards of care, what are the new and upcoming treatments. And many times I tell my patients in advance that I'm attending the meeting and then when I see them again, I like to update them on some of the things that we've learned about that are relevant to their particular lymphoma. So I think it's really important as a platform for us to learn what's new, what's up and coming, what doesn't work, and what looks like it might be changing practice.

Hannah (04:54)
Perfect. Thank you for that answer and for sharing with your patients after you attend the conference and as you hear some of this information. That's great. And then, can each of you share what you thought the most exciting or promising updates were for follicular lymphoma from this most recent conference? Dr. Casulo, maybe we'll start with you.

Carla Casulo (05:13)
Sure. So I think one of the things as we focus a lot on follicular lymphoma for research, I see that there were many abstracts that were focused on looking at new treatments for follicular lymphoma by bringing kind of new targeted drugs to patients earlier in their treatment course. So sometimes certain...

Medicines are only available to patients if their lymphoma is to come back after it's treated. But this time, we heard a lot about new treatments that can be moved up their lifetime. So instead of waiting for their lymphoma to come back, we can use them earlier. That was the case for follicular lymphoma as well as some other diseases. And then there were also some interesting practice changing.

abstracts that were discussed about how we approach certain rare forms of lymphoma like mantle cell lymphoma. So I think overall to me, the takeaways were that for some diseases, treatments are changing completely the way we approach them. And other diseases, it looks like there are a lot of new treatments that are very promising that we're gonna have access to earlier than we did before.

Judith Trotman (06:16)
Yes, I agree Carla. It was very exciting that we're now starting to get the long term follow up from some of these novel therapies. I'm sure a lot of follicular lymphoma patients have heard of the excitement around what are called the bispecific antibodies that harness the patient's own T cells to kill the lymphoma cells and likewise

the engineered T cells in the laboratory called CAR T cells that also can attack the lymphoma cells. Those trials are starting to mature and have several years of follow-up showing that in patients who get what we call as a complete response to these novel therapies, many of them are in a sustained response for a few years. And this is why, as Carla pointed out,

These novel therapies are, we're learning how to deliver them, how to minimize their toxicity. And they're being introduced in earlier and earlier lines of therapy. So not just in the patient who's already had three different treatment rounds, but patients who've only had one treatment round and even some early data about it being used in the first line setting, which is very, very. premature but it's you know looking promising.

Hannah (07:39)
So Professor Trotman, you did just mention this a little bit bi specific antibodies and CAR T therapy. Was there anything else that this ASH conference revealed about the role of immunotherapy in treating follicular lymphoma that you think would be helpful for patients to understand?

Judith Trotman (07:56)
Look, I think we're getting a better sense of the longer term complications of these therapies and in particular, not just the short term problems that people have in the first month or so, but challenges that are faced with supporting them in the years afterwards, in particular, supporting the recurrent infections that many patients have. And that's so important because you know, as follicular lymphoma patients are living longer, it's all about quality of life as well and how we can minimize these infections with preventative antibiotics, but also with immunoglobulin antibody infusions to support their immune system. So learning more and more about that was good and also starting to get a sense that we don't need to continue these bi-specific antibodies, you know, indefinitely. And there's some, you know, some good promising data about what we call fixed duration of treatment. Because, you know, we want to have our cake and eat it too. We want to, you know, control or potentially cure the follicular lymphoma, but we don't want to, you know, create too much toxicity to the patient. And we also want to get them off therapies, know, living a life that isn't dominated by their lymphoma and coming in and out of the hospital.

Hannah (09:18)
Definitely that's so important for patients to be able to live their normal life and not have to have everything tied to how often they have to come in for treatment and things like that. Dr. Casulo, did you have anything to add about CAR T or bispecific antibodies for follicular lymphoma?

Carla Casulo (09:34)
Yeah, I agree. As Dr. Trotman mentioned, there is a lot of long-term follow-up now that we get to see what are some of the late toxicities, what are some of the possibly second cancers that are emerging with some of these? Is there anything new that should lead us to maybe not consider some of these treatments? So yeah, I think that targeted agents are probably going to be replacing chemotherapy in many cases. There was also what's called a late breaking abstract, which are kind of the up and coming hottest cutting edge research studies that are presented at the meeting. Two of them happen to be in lymphoma. And then one of them was also in follicular lymphoma, which showed us that when you add on a new antibody to your standard kind of targeted treatment, it makes that work a little bit better. So I feel like that could also be practice changing. So I think a lot of what we're hoping to see and a lot of new and interesting considerations that I think are gonna make things a lot easier for patients.

Judith Trotman (10:30)
And it's interesting what Carla was talking about, you know, and that's the big question. Are these new therapies going to replace chemotherapy or are they going to be given as an adjunct with chemotherapy? And if they are, are they going to enable us to dial down the intensity of the chemotherapy? Are they also going to be given in concert with other immunotherapies like the standard antibody therapies that we already have like Rituximab and obinuntuzumab mean the problem is, and this is sort of in some ways the wonderful thing about clinical research in follicular lymphoma, as soon as you answer one question you create half a dozen more.

Hannah (11:11)
Yeah, definitely. There is a lot of exciting updates from this ASH about CAR T and bispecifics and other treatment options. So how do all of these updates impact current treatment options for patients with follicular lymphoma and what can they kind of look forward to?

Judith Trotman (11:12)

Well, I'll pass that one over to Carla because it impacts her current treatment a lot faster than it impacts mine here in Australia.

Carla Casulo (11:38)
Yeah, I think that with a lot of these new treatments becoming available earlier to patients, it very well may replace chemotherapy. I think it's probably too early to say that. But I can envision in the next few years, some of these studies being read out that are looking at, for example, chemotherapy plus one targeted drug or chemotherapy plus a bispecific in follicular lymphoma, for example.

And those are big, big studies that are going on all over the world. And I have a feeling that we're going to see some movement in how we approach this disease, which is probably a good thing. Because as Dr. Trotman presented at the meeting, this is a marathon. And patients are living with follicular lymphoma for many, many years. So we really want to be mindful of not hindering that survival by giving treatments that are too toxic. And that could potentially subject them to other untoward effects without sacrificing their ability to be potentially cured or go in to a long remission. So I feel like in the next few years, we're going to see a lot of change in how we practice. That's my prediction.

Hannah (12:47)
thank you both for that wonderful overview of ASH as a whole. It's great to see all the amazing work being done in this follicular lymphoma space. And now I'd like to move on to your education session, which was called Follicular Lymphoma: Playing the Long Game. And Professor Trotman, we will start with your abstract, which was called In Pursuit of a Functional Cure. And during your presentation, you argue that a functional cure is actually already being delivered to many patients. to start out, can you explain the concept of a functional cure and how this has even become possible?

Judith Trotman (13:23)
Sure, sure. think firstly, I have to say it was wonderful to do this education session with Dr. Casulo and Dr. Bartlett. We had a lot of fun and we're really out there challenging some of the of standard sort of concepts of follicular lymphoma, and in particular this one of it being an incurable lymphoma. And while that might be probable at a disease level.

It's at the individual patient level where I think cure is an underused word. And it's hard to define cure, isn't it? When life itself is incurable. But the concept in the true Latin sense of cura, to heal, to restore good health, is actually echoed in the formal National Cancer Institute dictionary of cancer terms.

I think our limited five to 10 year follow-up from clinical trials sort of encourages us to be a bit too conservative and pessimistic when discussing with our patients. But even that limited data and the population data we have supports much more optimistic prognostication. And I was basically putting it out there and providing some data, which I'm happy to elaborate on Hannah, that many patients with follicular lymphoma will achieve a functional cure and are predicted to die with rather than from their lymphoma. And that's become possible because of the addition of novel therapies such as rituximab and obinutuzumab antibodies to our standard chemotherapy approaches. And so that's going to become even more possible and perhaps probable with all the novel agents in clinical development and perhaps the most affirming statement that I can give to any patient who's newly diagnosed in 2024, 2025, listening today, is that modern survival is now so prolonged, I cannot make reliable survival estimates for them.

Hannah (15:28)
Thank you for that explanation of a functional cure. And it's definitely scary for patients to hear that they have an incurable disease. So I really love the way you frame this and how much more positive it is for patients to hear that they can have a normal lifespan and things like that.

And a lot of times with follicular lymphoma, watch and wait is a common approach for managing it.

But you also noted in your presentation that watch and wait often becomes watch and worry for patients. So what are some options for patients that remain worried after their diagnosis?

Judith Trotman (16:04)
Perhaps if we could just set the scene for that Hannah first before I offer that options. It's important to recognize that about a quarter and some studies more than a third of patients with follicular lymphoma have what we call is low tumor burden or asymptomatic advanced stage disease and they begin with that watch and wait approach. And sometimes for those patients, they can have a spontaneous regression of their disease. It's uncommon, but it's a recognized phenomenon. And the disease can wax and wane for years before it needs treatment. In one population study, about 40% of patients who underwent watch and wait had not commenced therapy with a median follow-up of eight years. And there was plenty of studies that sort of reiterate that sort of message. But in lieu of watch and wait if the patient is getting a lot of watch and worry, there are durable responses in patients who receive single agent Rituximab antibody therapy. But I think that's really important that anyone who embarks on Rituximab monotherapy needs to do it in a full understanding of what the goals of therapy are.

because certainly rituximab monotherapy is very well tolerated and it delays the need for chemotherapy in future years. And I say delays, it doesn't necessarily mean you don't need chemotherapy in future years. But I tend to use, and probably because I don't have the same easy access to rituximab monotherapy, but also I do, even if I did have access to it, tend to use the years of watch and wait to understand the tempo of my patient's disease to get a sense of how it's progressing, if it's progressing at all, and to socialize these concepts of functional cure and longevity, to focus on their prehabilitation given so many of my patients have now other chronic diseases and poor fitness. And I also remind them that if they've had rituximab monotherapy,

it may exclude them from study of these novel therapies in first line if they've already been out of the gate and had treatment. And so I tell them, I genuinely believe is that the best therapy is the one they don't need in such a rapidly changing therapeutic environment. I remember I had a very anxious woman in her 40s 10 years ago for whom the nine years of watch and wait were, despite my efforts, watch and worry. And we finally treated her because she sort of met criteria for needing treatment. She wasn't symptomatic, but her nodes had grown to a certain size that prompted time to treat. having treated her in 2024, she now acknowledges her worries have shifted to that of a relapse. So I'm not sure that, you know, watch and worry is completely obliviated by, you know, Rituximab monotherapy, because I think people who remain anxious often remain anxious and need that ongoing social and psychological support, even as you assure them that you're optimistic of, you know, very long remissions.

Hannah (19:20)
Yeah, definitely. That's a really interesting point actually that I hadn't thought of that a lot of patients who are anxious during the watch and wait period are still anxious after receiving treatment because of course, as we noted, follicular lymphoma is considered incurable. So no matter what, you know, if you're anxious, that's going to remain. So thank you for bringing that point up.

Judith Trotman (19:21)

It's their choice, you know, but it has to be an informed choice.

Hannah (19:44)
Yeah, definitely. And so how do you navigate some of these therapy decisions since there's so many treatment options and watch and wait available for follicular lymphoma patients?

Judith Trotman (19:56)
Look, it's very patient-specific approach and navigated over successive appointments and discussions with the patients. And that's often interspersed with their own Google search, which is fine. I tend to direct them as to what therapeutic approach is to read research on the internet. But the principle remains the same. I'm aiming for the most efficacious treatment that I think the patient can tolerate and tolerate well. And so the most immune suppressive therapies are given to my youngest fittest patients. And then I dial back the intensity of the chemotherapy as patients age. And I see Dr. Casulo nodding here. I think this is pretty standard approach globally. And not just as patient age, but as they start acquiring a few comorbidities, a few other health conditions and frailty even without specific organ problems. So for that reason, I don't often give bendamustine which is quite an immune suppressive chemotherapy to the elderly and prefer a more gentle sort of chemotherapy combination in those who need treatment. Obviously, if I'm very concerned that the patient may be transforming from a slow growing follicular lymphoma to something's more aggressive. Or if I've done a biopsy that shows they've got what we call a histologic transformation to an aggressive lymphoma, I will use a treatment called CHOP, which has a terrible name, but is very, very effective against this aggressive transformation.

Obviously, I'll always combine it with an antibody, either Rituximab targeted against the CD20 protein on the surface of the lymphoma cells or the next generation antibody called Obinutuzumab. whatever recipe for an individual patient that we decide to give them, there are efficacy and toxicity, what we call the eff-tox trade-offs to discuss with each patient when deciding that recipe. And then if we're talking about the initial therapy after what we call this initial induction therapy, I generally start antibody maintenance with that rituximab or obinutuzumab antibody. And I aim to give that for two years, but I only started in those who are what I call willing and well because while it has a clear effect on prolonging the remission duration, there is no overall survival advantage to using this maintenance approach. And it does come at a cost of reduced blood counts and infections. So I do stop it if it gets too toxic with too many recurrent sinusitis or bronchitis in patients, especially the elderly. And of course, I always make sure it fits in with their post-treatment travel plans because it's about their life and living well, not being tied to the hospital.

Hannah (22:59)
Yeah, thank you for that wonderful overview. And then can you share some of the survival data that you presented at ASH that may help patients and physicians have a more optimistic look?

Judith Trotman (23:12)
Yeah, look, there are so many different survival metrics that I can share. And so sort of think about what are some of the key ones that we've got from clinical trials. think the expectation from the large Prima study is that patients who achieve remission and go on to have that antibody maintenance that I was talking about will have a median of about 10 years before they need their next lymphoma treatment.

And another metric comes from the large gallium study in the sort of current treatment era that says that 90 % of these patients who achieve remission will be at that seven year mark. aside from clinical trial, we can look at population studies and sort of the aggregate of all the population studies that I've looked at suggest a good measure, a good metric to remember is that 10-year overall survival of 80 % and bear in mind that the median age of diagnosis is about 64 and death from lymphoma in that high-risk first decade after initial treatment is about 10 % of patients. I think when I was sort of researching all this, one of the most reassuring survival metrics that I got was that the 70%, the sort of two thirds of patients who remain well and in sustained remission at the two year mark after their treatment, and this sort of feeds into Dr. Casulo's talk later, that good risk patient population who do well two years after their completed therapy actually have age matched and gender matched survival. that is comparable to the normal population. then the last metric I like to quote when patients ask specifically, you know, how many lines of therapy will I need? How many times will I need to sort of face this follicular lymphoma with treatment is giving them this one to one to one ratio, sort of a rule of thirds. Because a third of patients, will receive no treatment or one treatment and another third will receive two lines of treatment and a third three lines of treatment of therapy in their lifetime. And if all those CAR T cell or bispecific antibody data proves to be promising, we will see those come down and potentially be used in the first and second line.

Hannah (25:52)
Yeah, all of that data is definitely really wonderful and helps have a more optimistic outlook on follicular lymphoma. So how do you patient stories and long-term outcomes help reshape the broader narrative around follicular lymphoma being incurable? And how can patients contribute to data to help us reshape this narrative?

Judith Trotman (25:52)

Okay, so I think you've already got a bit of a sense that I think that with so many patients living so much longer, many patients living well over 20 years, that our limited trials follow up data with five to 10 years of follow up is insufficient. Imagine telling the 6 % of lymphoma, follicular lymphoma patients who are aged less than 40, that the best estimates we can give them is a 90 % probability of being alive in eight years.

They want to know their probability of living more than 30 plus years. So our trials data is insufficient to tell patients. But we also have a very mobile global population. We're not just Americans and Australians, we're all citizens of the world and we're all moving around the world. And it's very hard to track us with our traditional registries.

So I feel very strongly that we actually need to go to source. We need to collect patient-derived data. And we need these self-recorded metrics from our patients to show that they're living both longer and better. I think in 2025, everyone's a digital native. And every individual story has greater power because it becomes part of that big data.

So we're pretty excited. That's one of sort of my research priorities for this next year. I've had experience in developing mobile app and web-based data sets of patient-derived data with other lymphomas, Waldenstroms and now with Hodgkin's. So we've got global plans for a followed for life app for follicular lymphoma patients in the next year. So hopefully any keen patient investigators listening out there who are interested in supporting them And being an investigator in this, do please reach out. we really do need to amplify the patient voice in this particular space.

Hannah (28:01)
Thank you so much for that wonderful overview of your abstract. And like you said, it's so important to get the patient voice in this space and it helps other patients down the line have a more positive outlook on their disease and treatment options. So thank you very much. And then Dr. Casulo we will now move on to your abstract, which was called the POD24 Challenge: Where do we go from here for early progressors?

Hannah (28:26)
So could you start out by telling us what POD 24 stands for and how it's defined in the context of follicular lymphoma?

Carla Casulo (28:34)
Sure, I'm happy to. So, POD24 stands for progression of disease within 24 months. And that essentially was a term that evolved from an observation that we made in a research project that about 20 % of patients, or one in five, will have recurrence of their follicular lymphoma within 24 months or two years. And so based on that observation, we wanted to understand whether that matters.

does it have any relevance to the patient if their disease comes back within 24 months? And so that led us to explore what impact that has on survival, what impact that has on their on transformation to an aggressive lymphoma. And we learned that unfortunately, patients that have POD 24 or who progress early will have lower survival compared to their counterparts.

who don't relapse within that period of time. So specifically, POD24 was defined in patients who are treated with chemotherapy. So chemotherapy plus immunotherapy, which is how we treat folliculone foma nowadays for the most part. However, it's been also looked at in patients who are observed, in patients who receive rituximab. And so while the impact may not be as pronounced in those patients who receive gentler treatment or who are observed,

It's still not as good biologically to have early progression. And most certainly, it's a worrisome finding if it happens after chemotherapy, because it tells us that there's some resistance, there's some biologic change in that disease that causes it to come back so soon. And we've learned that some of those patients have a different lymphoma when they relapse. Some of them have diffuse large B-cell lymphoma, which is a more aggressive form. And so I think that It's a very important observation and we're learning a lot more over the last 10 years as to what's changed, what's happened to help us understand this disease better.

Hannah (30:24)
And what are the typical outcomes for these patients with POD 24?

Carla Casulo (30:30)
So in the original publication, when you took about 450, 500 patients, those who had early relapse, they had a five-year overall survival of 50%, so meaning that half of those patients only lived about five years, which is a stark number.

On the other hand, if they didn't have any disease recurrence within 24 months, they had a 90 % chance of survival of five years.

Later on, we looked at this in a bigger group of over 5,000 patients. And this has also been studied across the world in many other data sets. We found that it may be closer to 70%, but still having a difference of survival of 70 % versus 90 % is still pretty drastic to someone, in my opinion. And so those are the main observations that that's the main kind of, I guess, difference in survival that you would expect with this development.

Hannah (31:30)
And what are some of the clinical and biological factors that have been identified as predictors of POD 24?

Carla Casulo (31:38)
I think that's sort of the holy grail in a way. A lot of people are asking that question. And there are, we know that there are a lot of clinical features of patients. having advanced stage, having, you know, certain clinical changes within their lymphoma, like higher grade, what we call a high FLIPI score, which is one of our prognostic markers, having certain mutations in their biopsy, although that isn't done routinely in follicular lymphoma. We don't perform mutational testing on everyone, but in those in whom we do, we've discovered that yes, that does have a role. So we know that there are clinical factors, what we call clinical factors that are patient-based, like lab tests and things like that. And then we have the molecular tumor-based characteristics. We've put a lot of these together to have new models that have said, well, if you mix the patient factor with the, you know, biopsy factor, maybe we can find something that can help us define with more precision who might be at risk. But they haven't really panned out. So we're still looking, we're still testing and understanding how that comes to pass.

Hannah (32:41)
Thank you for that. That'll be very interesting to see the clinical and molecular together, the research that comes out of that. And what treatment strategies are being developed to address the risk of POD 24 in follicular lymphoma patients?

Carla Casulo (32:56)
the majority of studies are looking at how to treat patients when that happens, when the POD24 problem happens. So we've discovered that a lot of patients actually respond really well to targeted treatments like new treatments like bispecifics and CAR T and things like that. It looks like just standard chemotherapy may not work as well.

And it probably makes sense because of what we call chemoresistance, which is what happens when lymphoma cells are exposed to chemotherapy and then not all of them die. Giving them chemotherapy again may not result in the best outcomes and the best results. the party line is that maybe giving patients who have early recurrence something new and different might be more advantageous. And so that's kind of where we're going.

In terms of at the time of their diagnosis when we meet them in the office, we really don't know with that such great accuracy, is this person going to be in that category and should I treat this person any differently? As of right now, the tools that we have are exploratory, kind of more research-based. So those are things that we are all as lymphoma doctors looking at, trying to understand and we're testing some of these models to say, well, let's see if we treat this group differently. And that's called adapted treatment, where we treat one group that's a little bit higher risk slightly differently than we would treat a group that's lower risk. And that's something that all of us within lymphoma are really excited about, myself included. So I think that's probably where we're going to end up, hopefully soon, but not quite there yet.

Hannah (34:28)
Thank you. And you mentioned this a little bit already, but why are new risk stratification strategies integrating clinical and molecular risk profiling needed? And what are some of the challenges with implementing these strategies into routine clinical practice?

Carla Casulo (34:46)
That's a great question. I think the biggest limitation is that a lot of the tools that are used to assess these mutations are just not available to the average doctor in the office. Even though I practice at a large academic medical center, some of these things are considered research still. And so if I wanted to use them rapidly to decide on who to treat, we're looking at sending the test out for specialized testing or even within our own group. The testing takes three to four weeks, which isn't so practical.

you're trying to decide how to approach treatment for someone. And so I think that the bottom line is that they're really not readily available for the day to day. So if that's the case at a major academic medical center, imagine in a community practice, maybe a small rural group where perhaps there's more limited resources or in a country where they don't have access to those types of things, it doesn't make for a very easily used way to say, hey, who with follicular lymphoma should we treat differently? And so I feel like those are the major limitations is that they're just not readily available. And then to your question of why do we mix these two models? Why do we use clinical and molecular models? the clinical tools aren't super precise and then the mutational tools aren't super precise. So the idea is if we put them together, maybe we'll increase the likelihood that we'll capture more patients.

Hannah (36:05)
Thank you for that, wonderful overview. I like how you mentioned that these treatment options are not readily available for patients all the time. I know that's an issue that many patients face with new treatments that they're excited about. So of course, I'm excited to see what happens with this profiling that is being worked on and hopefully. we can get access to patients soon as well. And then my last question for you is what further research is needed to develop effective models for identifying and treating patients at risk for POD 24?

Carla Casulo (36:40)
So another great question. think having people that are invested in this and really have a passion for it, as myself and Dr. Trotman were really passionate about this disease. And we think about it a lot. And we are always thinking about ways of helping patients. So I think putting brain power together, helping to be creative and innovative about how we can identify patients better, not just for POD 24, but for other things like transformation.

Or on the other hand, who is going to do phenomenally well and we can leave them alone and have them have a perfectly healthy normal life without worrying about their disease. I feel like that's just as important for someone to know when they meet you because you can really just help them take a deep breath and just be okay. Know that they're going to be okay. I feel like that's super valuable. So I think brain power, creativity, innovation, merging of the minds and collaboration is the is key to getting this, moving the field forward.

Judith Trotman (37:40)
Absolutely, I think what Carla says about collaboration is just so important. Collaboration with basic biological scientists, molecular scientists, collaboration with our industry partners who are developing these novel new therapies. And the patients who have POD 24, the patients with histologic transformation,

patients who have multiply relapsed disease, they're significant minority populations and those partnerships with industry really drive us to find better solutions for these patients. But I just want to echo again what Carla said. You know, there is a majority population who do very well and we need to better identify that majority as much as identifying the minority who really need extra special attention.

Carla Casulo (38:37)
Absolutely.

Hannah (38:42)
Absolutely. Thank you. Like you both said, collaboration will be so important for moving the field forward, not just for POD 24, but for everything relating to follicular lymphoma. my final question is what message from ASH should give patients hope about the future of follicular lymphoma?

Judith Trotman (38:43)

Oh, well, I think the key message is that there is more than hope. There is a growing certainty that most patients with follicular lymphoma can live a long life in mostly good health, empowered by all those therapies that we have and those that are emerging.

I tell my patients at diagnosis that I have every expectation that they would live to be an old woman or an old man. And that's the baseline that we should be setting for ourselves, even if there is a minority who don't achieve that.

Carla Casulo (39:37)
I completely agree. I think to practice medicine, you have to be an optimist. But that's especially the case if you're a lymphoma doctor. And I'm always a glass half full person. I'm always super excited about new things and treatments. And I feel like it's only an upward trajectory. So I'm very excited about what the future holds. I feel like the ASH meeting always leaves you with that sense like you're brimming with hope that good things are to come. it's just like, it just fills you with a lot of energy and you come out of it like, I'm gonna do this, I'm gonna do this, I'm gonna do that. And so I feel like it's just, it just really energizes you and it's a great way to know that other people feel the same as you do about this.

Judith Trotman (40:18)
And that's one other thing perhaps we could finish up by pointing out. Come back full circle to about the ASH meeting and the attendees. Hannah, there are people like you, there are people who are leaders of some amazing patient organizations and there are a lot of follicular lymphoma specific patient organizations around the world who are now at the table and who are insisting quite rightly that they have a say in the design of trials, in the conduct of trials, in the prioritization of the research that we do. Because we as clinicians, can get overexcited with the biology and the bad players. And we really are increasingly recognizing that this is a partnership that we do have with our patient and their care community.

Hannah (41:10)
Absolutely. Thank you so much for that shout out. definitely feel very grateful that I get to bring the patient voice to these conferences and clinical trials and everything that I work on. It's so important. thank you both so much for your overview of your sessions and the ASH conference as a whole. This has been super informative and I've loved getting your perspective of hope and optimism for our follicular lymphoma community here at Health Tree. So thank you again so much for joining us today and sharing the incredible work you're doing on behalf of follicular lymphoma.

Carla Casulo (41:45)
Thank you, Hannah. I'm so grateful for the invitation as well and just really so happy that you're a part of this and helping patients get the

Judith Trotman (41:45)
Absolutely.

Hannah Loosle (41:56)
I loved this interview. It was so great to hear about all of the exciting things that came out of ASH for follicular lymphoma. It was really hopeful to hear Professor Trotman talk about the way we can reframe follicular lymphoma from being incurable to being able to achieve a functional cure for many patients.

I also appreciated Dr. Casulo's remarks about how important innovation and collaboration are to move the field forward as it relates to not only pod 24, but every aspect of follicular lymphoma. The conversation was so informative and uplifting really provides a lot of hope for the future of follicular lymphoma treatment. you want to keep learning about the ASH conference or any of the specifics we talked about today, we have some additional resources you can look at related to today's topic. We have tons of ASH recap videos and articles that I will link in the description.

Thank you for joining us today on the Health Tree Podcast for Follicular Lymphoma. I hope you learned something new. us again next time to learn more about lymphoma research and what it means for you.