What: Embargoed press briefing on Hodgkin Lymphoma research from the Wilmot Cancer Institute at the University of Rochester Medical Center, with a new study to be published in the New England Journal of Medicine (NEJM). The embargo lifts at 5 PM ET on Wednesday October 16, 2024.
Who: Johnathan Friedberg, M.D., M.M.Sc., Director of the James P. Wilmot Cancer Institute
PIO Contact: Susanne Pallo - [email protected]
When: October 14th, 2024 at 11 AM ET
Where: Newswise Live Zoom Room (address will be included in follow-up email)
Moderator: Hello and welcome to today's newswise live event. We have a virtual briefing about Hodgkin lymphoma research with Dr. Friedberg from University of Rochester Medical Center. Dr Friedberg, please introduce yourself and tell us a little bit about why this study into Hodgkin lymphoma is important, and what we need to know to understand that?
Dr. Johnathan Friedberg: Hi there. Jonathan Friedberg, I the director of the Wilmot Cancer Institute at the University of Rochester. I chair the lymphoma committee of SWOG, which is an NCI funded study group to conduct clinical research nationally. I'm also editor in chief of the Journal of Clinical Oncology, and I've dedicated my career to studying novel therapies in lymphomas. Hodgkin lymphoma is a rather uncommon type of cancer. However, it disproportionately affects younger patients, the median age of patients diagnosed with Hodgkin lymphoma may be around 30, meaning half the patients are younger than that. Hodgkin lymphoma has been one of the greatest success stories in oncology. In the 1960s this was a uniform death sentence for patients, and now the majority of patients, in fact, the vast majority of patients with Hodgkin lymphoma are cured. However, there are a few issues that remain in Hodgkin lymphoma and in Hodgkin lymphoma, because we have been so successful, it's often served as a template for study of other cancers. Remaining issues for Hodgkin lymphoma include with advanced stage presentations or more aggressive presentations. There's still about 20 to 25% of patients who are not cured, and those patients need to go on and get significant toxic therapy in addition, because these are younger patients, they frequently have 50 or more years of life remaining after treatment, and what we've learned is that some of our successful treatments in the past have caused significant late side effects. So it's in that context that we leveraged this new trial.
Moderator: Reminder for media on the call the topic and the results of this study are under embargo. They're going to be published in the New England Journal of Medicine. That embargo lifts on Wednesday the 16th, at 5pm Eastern. Dr. Friedberg these existing treatments have been a big success. As you said, your study takes things further with even more successful treatment, better survival and avoiding some of the complications and future secondary cancers that can develop. Tell us a little bit more about how that has improved and why that's important?
Dr. Friedberg: Yeah, this was an exciting, really trailblazing study for several reasons. This is the first study in the United States that has included both the pediatric and the adult group of patients together. Historically, patients cared for by pediatricians or patients under the age of 18 were treated slightly differently from adult patients using different chemotherapy backbones as well as more radiation therapy, and due to a series of meetings that occurred between our adult study groups and the pediatric study group, we harmonized our approach within the context of this trial, such that a third of patients enrolled on this trial were enrolled by pediatricians. The trial took the current standard regimen, which includes a chemotherapy regimen called AVD, each of those letters stands for a drug, along with a drug called Brentuximab Vedotin, and that's the standard treatment. And half of the patients were randomized to that treatment. The other half of patients got the same AVD, chemotherapy, backbone, but instead, I got a immune therapy called Nivolumab, which is an approved drug for several other cancers, including the relapse setting and Hodgkin lymphoma. But this is one of the first large studies of this drug as part of upfront treatment of Hodgkin lymphoma. This was a one to one randomization, and in addition to including the younger patients that I mentioned, this was also open to all ages of patients. We were happy to see that the enrollment resulted in a very diverse group of patients. 12% of the patients were black and 13% of the patients came from Latino backgrounds. This means that these results can be exportable to broad patient populations, over 200 sites across the United States and Canada enrolled patients to this trial, and the results really surprised all of us and how positive this was only one year in follow up, the data safety monitoring committee recommended closing the trial early because the signal was so great that the new regimen had improved efficacy compared to the old regimen. We waited an additional year in follow-up to report these results, because we wanted the results to be meaningful, and now, with two years of follow up, the trends are actually higher, such that we're curing substantially more patients with this regimen. And in addition, the regimen was less toxic than the previous regimen. Finally, because I mentioned radiation therapy as being something that was used for the pediatric population, only six patients in the entire trial that enrolled close to 1000 patients actually received radiation. So we've largely eliminated radiation therapy as part of the treatment, and taken together, we now have a more effective, less toxic regimen that should not only have less short term side effects, but also less long term side effects, harmonized for both children and adults in the treatment of Hodgkin lymphoma.
Moderator: You mentioned that this new approach takes an immunotherapy drug and incorporates that into the chemotherapy. Can you tell us a little bit about how that immunotherapy drug works to allow the body to target the cancer?
Dr. Friedberg: Yeah, so this is a class of drugs called checkpoint inhibitors. And what this class of drugs does, the way I think about it, is it takes the brakes off of the immune system. And one of the reasons why cancer spread is because the body's own immune system, which normally may help fight cancer. The cancer largely paralyzes that immune system, and this drug helps to take the brakes off the immune system and helps the immune system start to fight the cancer. The story in Hodgkin lymphoma, though, is a bit more complex than that. The malignant or cancer cells in Hodgkin lymphoma have a specific chromosomal problem that results in exquisite sensitivity to this type of treatment, this checkpoint blockade, and we leveraged that sensitivity in this trial, and in fact, we have some correlative studies ongoing to try to investigate further subsets of patients that may be most vulnerable to this treatment. That said, the fact is that greater than 90% of patients two years later still remain free of Hodgkin lymphoma. So this is really broadly applicable to almost every patient with that disease.
Moderator: And if you could tell us a little bit about whether this can be implemented immediately, how are oncologists permitted and encouraged to start treating patients this way?
Dr. Friedberg: Right, We did report these results a year ago in preliminary form at a meeting, but most providers wait for a peer reviewed manuscript, which, as was stated, will be published later this week. We're optimistic that, based on the publication of this manuscript, many physicians and practices will quickly change to this new regimen. All of these drugs are approved drugs, none of them are experimental, and because the regimen is less expensive than the previous regimen, less toxic and more active. We anticipate that guidelines will rapidly change to recommend this as a preferred treatment option. Accompanying the paper in the New England Journal of Medicine is an editorial written by two other experts, and what you will see in that editorial is also a recommendation that this become a standard of care quickly.
Moderator: I'd like to introduce another guest that we have today, Jenna Cottrell, who is a survivor herself of Hodgkin lymphoma and works in the media in the Rochester region. Jenna, I'd love if you could introduce yourself and tell everyone a little bit about your experience recovering from Hodgkin lymphoma.
Jenna Cottrell: Yeah. So Hi everyone. My name is Jenna Cottrell. I work at the ABC station here in the Rochester area. I'm a sports reporter. I. I was diagnosed with Hodgkin's lymphoma back in 2017 when I was 25 years old, I went through 12 rounds of the ABVD chemo that was mentioned earlier, and I think my journey might have been a little bit more public due to my job in the community and hearing about the study and the advancements that we're talking about today made me a little bit emotional early on, because I know how life changing this will be for so many future patients. I know for myself. I, You know, bounce back from treatment really well. I've been in remission Since 2017 but the physical toll that it did take on my body, both, you know, mentally and also emotionally, was something that you know, it's a challenging journey. So to hear about the advancements, and I just can't help but feel so positive for future patients, because to hear about a treatment that works so successfully and is less taxing on the body, is just really, really encouraging, and I'm really thankful to hear about this study. And yeah, my journey was definitely something that I feel like for a lot of Hodgkin's lymphoma patients, they were not expecting again, I was just 25 but I learned a lot about myself through that journey, and to hear that other patients will have a lightened load, hopefully, is really awesome to hear.
Moderator: One of the things that this study predicts is that the risk of secondary cancers later in life, that is very common with Hodgkin lymphoma patients may be reduced. What's that like been in your experience, to be sort of vigilant about or getting regular screenings to make sure that you're not developing something somewhere else in the body. How does that feel? And what's that like for patients?
Jenna Cottrell: I mean, I'll be honest, it's very stressful. It is very anxiety inducing. I mean, for me, I feel like I am acutely aware of my body now and how it responds to things, and I'm very diligent about how I take care of myself. But I describe it to my friends as like, if your house is broken into and you hear a bump the night later on, your sometimes immediate reaction is, Oh no, it's happening again. And so having the knowledge that patients in the future might not have to be as vigilant and as stressed out about something like this is definitely really important to hear. And you know, I stay on top of all my doctor's appointments. Some of my friends probably think I'm crazy, but I like to, yeah, just I feel like you can realize how much of your life can be out of control. So by being someone that does take proactive measures, I think that's important. But, I mean, yeah, it's absolutely something that I think about a lot, and to know that maybe people in the future won't have it such a heavy burden of that is, it makes me happy for them, Truly.
Moderator: Dr. Friedberg, how do you think that this new treatment protocol might change the math a little bit for patients like Jenna and having to stay on top of checking for being concerned that another cancer might develop?
Dr. Friedberg: I will emphasize, it's certainly important that we follow the patients enrolled in this trial for longer period of time, and we do have plans to do that to ensure that what we predict will be the case, but it is clear that perhaps the highest risk of second cancers occur in patients who get radiation therapy, particularly young women who get radiation therapy to the chest because of the risk of secondary breast cancer, and with the ability of this regimen to largely eliminate the need for radiation therapy, we're certainly optimistic that some of those risks and concerns will go away. And I'll add that, you know, the cost and the follow up of this, you know, to try to do a trial where you're following patients for long periods of time, particularly younger patients who tend to move around and, you know, get jobs in different cities and that type of thing. It's a huge effort, and we would only have been able to do this with the support from the National Cancer Institute. Generally, industry is less interested in these relatively uncommon cancers like Hodgkin lymphoma, to primarily fund trials. So we're fortunate that the National Cancer Institute funded this trial, and it was conducted under the auspices of the National Clinical Trials Network of the National Cancer Institute that appreciates the importance of not only conducting these trials, but performing the long term follow up and ensuring that we learn as much as we can. And I'm privileged to be able to work under that banner, the swad group that is part of that National Clinical Trials Network to conduct impactful studies like this.
Moderator: Jenna, the hope is that this is going to also have fewer side effects for people getting treated for Hodgkin lymphoma. Can you share a little bit about what the challenges were like for you with getting treated?
Jenna Cottrell: Yeah, I mean, I think that they're pretty widely talked about just the fatigue and nausea, just I felt really weak. And you know, when you're 25 you're not used to feeling not invincible. So I think that hearing about things, maybe being less toxic, is definitely really awesome to hear. And I think for me, it was just mentally, honestly, was the hardest part. You know, physically I felt not good a lot. You know, I'd have moments and days that I felt a lot better. But for the most part, I think for me, it was the mental component of just feeling not good all the time and so, yeah, I think that this could be hugely beneficial for so many people. Because for me, it was just, you know, it was really hard to see. I ended up losing my hair, and that was really hard to go through treatment and then look in the mirror and not even realize and recognize yourself. So I think that just alleviating some of the systems as the some of the symptoms that feel so overwhelming at times, or at least helping really would go a long way for so many people.
Moderator: Thank you for sharing Jenna so that media here on the call can have a little more context for what this new drug treatment protocol might change for future Hodgkin Lymphoma patients. Dr. Friedberg, tell us if you can a little bit more about what next steps are for you with this research.
Dr Friedberg: Yeah. So a few things. One is, I want to emphasize, in addition to this study having such an impact on younger patients, another unmet need in Hodgkin Lymphoma is the uncommon presentation in older patients, specifically patients older than age 60, and that's a group that's really been largely unserved by previous clinical trials, and has not enjoyed the high cure rates and outcomes that I described earlier. This regimen, 10% of the patients enrolled on our trials, so about 100 patients were older than age 60, and those patients appear to do almost as well as the broader group, so we're optimistic that this regimen can largely quickly be adapted for the majority of older patients with this disease and affect their outcomes as well. One of the things we're looking forward to as far as the next step is some of the correlative studies from this we've drawn blood samples in patients over the course of treatment, and we're hopeful that those blood samples may allow us to do a couple of things, potentially develop an assay to predict patients who are not cured with this earlier so we might be able to intervene at an earlier stage, and also because it was a randomized trial comparing the Brentuximab Vedotin drug, to the Nivolumab drug, see if there are any subsets of patients that may differentially benefit from those two approaches. And we anticipate that the next study in this area will leverage some of those blood tests in order to make more of a precision approach for the treatment of Hodgkin lymphoma.
Moderator: And Dr. Friedberg, tell us a little bit more about your role there at the cancer center, and what's going on at the Wilmot Institute.
Dr Friedberg: Yeah, so at University of Rochester, I've been the cancer center director here for about 10 years. We have a very busy clinical operation and clinical program here, and in fact, we accrued the second highest number of patients nationally on this trial, right here in Rochester. We were only behind MD Anderson Cancer Center, which is the largest cancer center in the country. As far as accrual we have three large research programs here spanning the spectrum from basic science research all the way to population health and implementation science. And specific areas of expertise at Wilmot include aging and cancer as well as blood cancers and the cancer microenvironment, which means, how would the immune cells and other cells impact outcomes of cancer. Moving forward, we're looking to further build our clinical trial portfolio. Through earlier stage studies, and it's been a terrific privilege working here. But you know, this particular trial was really a testimony to collaboration all across North America, because it included Canada as well, and we have enjoyed the benefits of that through this robust result. And I think it demonstrates how for an uncommon cancer like Hodgkin lymphoma, when entire study groups get together and work together, we can really make a substantial difference for patients like Jenna.
Moderator: If anyone on the call has further questions, feel free to chat those, and I'll ask them to Dr. Friedberg for you, or if you'd like to ask them. After this is concluded, I've sent into the chat the contact information for Susanne at the University of Rochester Medical Center. She can help you to get in touch with Dr. Friedberg or to Jenna Cottrell if you'd like to ask her any questions as well. A reminder, also for everyone that this study is under embargo. It will be published later this week in the New England Journal of Medicine. The embargo lifts at 5pm eastern on Wednesday, October 16. So we ask that you not publish anything about it until after that time. And Dr. Friedberg, this is something that affects young people, and although it's considered a little bit of a rare cancer, people often considered to be particularly tragic because it can impact somebody at such a young age. Tell us what that means for you in terms of giving these young patients who you'd never dream would have had to deal with cancer, give them a little bit better approach to treat that and get through it.
Dr. Friedberg: Yeah. I mean, I think Jenna poignantly described the challenge of this disease, particularly as it presents at younger people, although I think certainly for any individual, when they get a diagnosis of cancer, it's an immediate life altering event. The Challenge at young people is that you know, many of the patients who I take care of are college students, or graduate students, since we have the university here, or people you know, like Jenna, who were just at the start of their careers, and it really interrupts life for six to 12 months. And even if the ultimate outcome is going to be very positive, for many people, that life alteration can have a profound impact on the direction of their life, where they go, you know, are they gonna go return to school? Are they going to shift jobs? And you know, it's we do our best to support people through that, but the more the treatment can be refined to be less obtrusive, have less side effects and enable patients to more quickly get back into a sense of what we'll call normalcy. I think that has significant impact for people that's hard to measure in in some sort of scale. But you know, we will learn, in addition to the blood tests that I mentioned, we're doing a number of surveys of what's called patient reported outcomes in this to try to learn what the real impact of Hodgkin lymphoma in general and these specific treatments are on people, and to say that, even though patients may be reporting less side effects, are there stress and mood alterations? And you know, some of the challenges that Jenna articulated, we're going to be able to capture those in a quantitative way so that we can understand, moving forward, how we might be able to intervene.
Moderator: A question here in the chat from someone in the audience, is this the first time this kind of therapy has been tried in Hodgkin's, is the first attempt at an immunotherapy to treat Hodgkin's?
Dr. Friedberg: So in the relapse setting, the immunotherapies have been tested before and are known to be active in the upfront setting, there were a couple of small studies, like studies that enrolled about 30 patients that demonstrated the safety of the combination. And before we opened this very large national study. We needed some of those preliminary data. Those were in general, single institution experiences at some of the large cancer centers. So this is the largest study to date, and really the definitive study of this regimen.
Moderator: And what do you think is next on the horizon for immunotherapy as applied to treating cancer?
Dr. Friedberg: Well, I think we're in the midst of an immunotherapy revolution in the treatment of cancer. For decades, people tried and it failed, and within the last 6 to 10 years, we've seen dramatic changes in. Not just Hodgkin lymphoma, but many more common cancers like lung cancer and melanoma. You know, I think we've heard that Jimmy Carter celebrated his 100th birthday, and we knew that for the last 10 plus years, he's had metastasis in his brain that were treated with immunotherapy drugs similar to the nivolumab drug that we used in this trial that said, unfortunately for many of the more common cancers, although immunotherapy seems to work, it's not a definitive cure, and a lot of the research now is looking to join immunotherapy with other standard approaches to see if that one two punch, so to speak, may ultimately be curative.
Moderator: A question in the chat you mentioned that this information was previously reported, was that at a medical meeting, or where was that?
Dr. Friedberg: It was previously reported last year at ASCO, the American Society of Clinical Oncology, as a plenary abstract. So not 2024 but 2023 ASCO, it was presented there.
Moderator: Okay, thank you, Dr Friedberg. If we have any other questions, please feel free to enter those into the chat. We have another question, what about Hodgkin lymphoma made it ideal for this treatment?
Dr. Friedberg: So again, I think a couple of things. One is the specific vulnerability that we know the Hodgkin lymphoma cells have that makes this treatment particularly impactful. And in the relapse setting, the response rates of single agent nivolumab in Hodgkin lymphoma are higher than just about any other cancer or any other cancer, so that made it particularly promising to bring this drug as part of the upfront setting. The issue, though, is, and the challenge is, that when you have a disease like Hodgkin lymphoma that is curative, you have to be somewhat conservative in making changes. You wouldn't want to take patients like Jenna and give them a new regimen that is like it's not as effective, because if you have a treatment that is working and curing most patients, you have to be very careful on how you build upon that. And it was really the balance of the significant promise of efficacy which fortunately bore out, as well as the understanding that this was less toxic, that made our study group particularly enthusiastic to move this forward.
Moderator: Another question from the chat, how concerned were you that the patients had neutropenia, as compared with this is a little bit in the weeds for me. But how concerned were you that 232 patients had neutropenia of grade three or higher as compared with the patients with the other treatment regimen?
Dr. Friedberg: Yeah. So I think the question is referencing, if you compare the side effects between the Brentuximab and the nivolumab. A lot of the side effects are driven by the chemotherapy and are going to be in both arms. But it was clear that most of the side effects had higher levels with the Brentuximab as compared to nivolumab. The one side effect that we saw that seemed higher in the nivolumab arm was neutropenia, and that's low blood counts, low white blood counts that can result in an increased risk of infection. Now, the subtlety here was, in the trial, we knew that neutropenia could be a risk with the brentuximab, so we required or mandated the use of what's called growth factor support or treatment to help abrogate the neutropenia in the brentuximab arm, and greater than 90% of patients actually got that treatment in the nivolumab arm, where we were hopeful that this wasn't going to be necessary, only 50% of patients actually got the treatment to help abrogate the neutropenia. So it's really not surprising that we'd see a slightly higher risk of neutropenia. The issue isn't so much the neutropenia in itself. It's, you know, did that neutropenia lead to infections or hospitalizations or fever and neutropenia which is really the dreaded risk, and we did not see that, so it seems to be more of an isolated laboratory issue, rather than something that was of consequence leading to increased infections.
Moderator: And if you could give us just a layman's understanding summary of neutropenia.
Dr. Friedberg: Yeah, so, one type of white blood cell is called the neutrophil, and the neutrophil’s job is to help fight infections. And when you give chemotherapy to patients, in addition to killing the cancer cells, it can kill some normal cells. And some of the normal cells that are particularly vulnerable are the neutrophils. And if you knock the neutrophils down too low, patients can be vulnerable to significant infections, and sometimes those infections can be life threatening. So that said, this is part of the cost of doing business right now. And in fact, you expect neutropenia to occur with many of the chemotherapy regimens we use for lymphoma, and as I mentioned or implied in the last response, we do have some agents that we can use to help at least shorten the duration of neutropenia. And the number of patients on this trial that had to be admitted to the hospital for infection or develop severe infections were not higher despite the higher rate of neutropenia in the nivolumab arm, in fact, they were lower than what we saw with brentuximab.
Moderator: And therefore the risk of getting those infections at a level of severity that they would have to be hospitalized. You're saying that your immunotherapy approach was, was performing better than the traditional approach?
Dr. Friedberg: Correct, that's right, yep.
Moderator: Any other questions for Dr Friedberg, please feel free to chat those to us. Another question here about the two year survival rate you achieved a 92%, would it be accurate to save this effectiveness was 92% or what would you what?
Dr. Friedberg: Yeah, so the 92% refers to what's called progression free survival. So that's not simply overall survival that also includes, you know, basically what we're saying is that at two years, 92% of the patients did not relapse, did not have progression of Hodgkin lymphoma and did not die. So you know, it was a composite endpoint that included all of those issues. If you look at overall survival, it was higher than that, as you would expect early on in Hodgkin lymphoma, because even if somebody relapses with Hodgkin lymphoma, they can sometimes live for a long time. The standard endpoint in studies of Hodgkin lymphoma is progression free survival, because we think that best predicts the future if you can keep people disease free and alive for two years. Generally speaking, it's very unlikely that beyond two years, you're going to have a lot of events. And therefore we're quite optimistic these results are going to be durable. But of course, it's going to be important to follow these patients for a longer period of time.
Moderator: Tell us a little bit about how you'll perform that follow up process, and for how long with these trial participants?
Dr. Friedberg: Yeah, so written into the trial, we have expectations, and it's really part of clinical care that patients will be seen a few times a year, initially and then annually through at least year five, occasionally. During those visits, they will also have imaging to make sure that the disease is not recurring. So those formal visits will be captured, and you know, we'll be able to provide study updates moving forward again. Parallel to those clinical evaluations, will be the patient reported evaluations, and some of those things will get to the point of, like, you know, how, how many of these patients who are interested can become pregnant? Are there fertility concerns, the you know, some of the lifestyle issues that Jenna mentioned, how many of these people are, are working and are, is depression and anxiety an issue? So we're going to be capturing all of those types of things in follow up. And because the National Cancer Institute is funding this, we have the ability to follow patients for even a bit longer than would be conventional, because we think it's gonna be very important, given the youth of these patients to have an understanding even eight to 10 years later, how they do.
Moderator: Thank you, Dr Friedberg, with that, we'll wrap things up. Just a quick reminder for everyone, these study results are under embargo until Wednesday the 16th, at 5pm Eastern. They will be published in the New England Journal of Medicine. If you have further follow up questions you'd like to ask Dr Friedberg or Jenna Cottrell, please contact Susanne at the University of Rochester Medical Center. I've put her contact information into the chat once more. We will have a video and a transcript available for this if you've already registered to attend today's event, you're on the list to get those once we have those pieces of information available, and if you didn't register and you'd like to receive those, please send an email to [email protected] so that we can add you to that list. With that, I will say thank you to Dr Friedberg and to Jenna Cottrell and to everyone at University of Rochester Medical Center and the Wilmot Cancer Institute for working with us to put together today's event. Thank you all very much for joining namaste and good luck.
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