ASCO: Amulirafusp alfa

 As I have been saying, there really weren't a lot of presentations on Follicular Lymphoma at ASCO this year, and most of them have been focused on treatments that are already established.

But there is at least one presentation on a newer treatment. It's one that I haven't written about before. (To be clear, I'm not saying that I manage to write about everything FL-related. But this is definitely one that I haven't mentioned before.)

The presentation is Abstract #7051: "Phase II safety and preliminary efficacy of amulirafusp alfa (IMM0306) in combination with lenalidomide in patients with relapsed or refractory CD20-positive follicular lymphoma." I actually remember reading about this when I looked at abstracts from ASH in November and December, but for whatever reason, I decided not to write about it. The ASH presentation looked at phase 1 trial results. This one looks at phase 2 results.

In this research, a treatment called Amulirafusp Alfa is given in combination with Lenalidomide (also known as Revlimid, one of the Rs in R-Squared). Amulirafusp Alfa is a very interesting treatment. It worls in ways that are similar to a bispecific, but it isn't a bispecific (which attaches to a protein on a lymphoma cell, and to a protein on a T cell, a kind of immune cell, bringing them together so the T cell can elimiate the cancer cell).

Amulirafusp Alfa works by targeting two proteins on the lymphoma cell. One of them is CD20, the same protein that is targeted by Rituxan and by some bispecifics. But it also targets CD47, another protein on the cell. By attaching to CD47, it blocks something called SIRPα (Signal Regulatory Protein a). When CD47 and SIRPα interact, they send a "Don't Eat Me" signal to the immune system. When that interaction is blocked, the immune system can eliminate the lymphoma cell.

And just as a bispecific is an immunotherapy -- it allows the body's T cells to work against cancer cells -- Amulirafusp Alfa allows other (even more powerful) immune cells to work against the cancer cells, in this case Macrophages and NK/Natural Killer cells.

This phase 2 trial involves 34 patients with Relapsed/Refractory FL. All of them had a previous treatment with anti-CD20. In the study, 22 patients were evaluated; 10 of them had a Complete Response (45%), 8 had a Partial Response, making the Overall Response Rate 82%; 2 more had Stable Disease. As for safety, the side effects were considered "well-tolerated," with most pateints having descreased blood cell counts of different types, another 35% having an infusion-related reaction. About 65% of patients had a more serious (grade 3 or higher) side effect. 

It certainly seems like a promising treatment, one that works in ways that are different from what we have seen so far.  It will be interesting to see updated figures (only 22 of the 34 patients in the phase 2 trial were evaluated), and to see how this treatment goes in a larger phase 3 trial.

Definitely one to keep an eye on.

ASCO: FL Subtypes

 Before I get to another ASCO presentation, I want to provide a link to the webinar I helped with last week for the Follicular Lymphoma Foundation.

The webinar is called "FL Treatment Options: What You Need to Know." It features Professor Andrew Davies of  the University Hospital Southampton in the UK, who did an amazing job of explaining the treatment options available to us in  an easy-to-understand way, and Dr. Mitchell Smith, the Chief Medical Officer for the FLF, who asked great questions and found ways to connect what I was saying as a patient and what Prof. Davies had to tell us as a Lymphoma expert.

I really enjoyed doing it, getting to share my experiences as a patient. I really like the messages that the FLF tries to get across, especially the importance of being an informed patient who can have a good conversation with their oncologist and ask the right questions. We have a lot to be hopeful about. 

The webinar is about an hour long. I hope you can find some time to watch it. 

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Now, on to the ASCO abstract for today.

I was really interested in #7070 "Clinical and biological subtypes of follicular lymphoma revealed by tumor and immune cell states."

As you read more about Follicualr Lymphoma, one word that you see over and over is "heterogeneous," which basically means that there are lots of different types of FL. If you spend any time in an online group for FL patients, you'll see how this plays out. You'll have someone like me who could watch and wait for a couple of years and then have a very long response from just Rituxan, And you'll also encounter someone who had a very aggressive FL who needed traditional chemo and maybe several other treatments after that. And you'll have other patients with experiences somewhere in between. 

This heterogeneity of the disease makes it a challenge to treat. Very often, patients don't know if a treatment will work until they've had the treatment. In an ideal world, we'd have a better sense of that before treatment began, perhaps by a biomarker. A biomarker is some biological component (maybe a certain protein on the cancer cell, for example) that would let the doctor know that a certain treatment is more likely to work, or maybe more likely to be aggressive or transform, allowing the doctor to at least narrow down the choices of treatment. We don't really have that yet.

Every now and then, someone proposes some kind of scheme for classifying Follicular Lymphoma into subtypes, allowing us to have a better sense of what we might expect. FL will always be heterogeneous -- that's unavoidable. But it would be great to more accurately categorize that heterogeneity.

This ASCO presentation is the latest attempt to do that. They try to create categories of FL based on characteristics of the cancer cells themselves, but also characteristics of other immune cells. They looked at several thousand samples of FL cells, and found four different subtypes of FL. It's kind of hard to distinguish the four types, and in some ways, the details don't really matter at this point. It will require a larger study to see what the real world implications are, and if this proposed scheme even holds up.

They do identfy two possible future targets for future treatments -- CREBBP (CRE-Binding Protein, which is involved in cell growth) and PRDM15 (a protein involved in differentiation, where an immature cells grows into a specific type of cell).

Will those targets result in new, effective treatments years from now? Will the subtypes hold up and help doctors make better treatment decisions? Hard to say, at least for now.

But what I find most interesting is what it all says about where we are right now. For all of the progress that has been made in developing new treatments, there is still so much that we don't know.

And I find that oddly comforting. If researchers said "Well, it looks like we've tried everything, and nothing works," that would be sad. But we're constantly getting new possibilities, learning more about FL, even when things don't work out as we'd hoped. Researchers will hit on something soon -- maybe not tomorrow, maybe years from now. But we're always moving forward. I find that really hopeful.

More ASCO stuff soon.

(And remember to watch that FLF webinar when you get a chance.)

ASCO Review: Clinical Trials and Surrogate Endpoints

As I said in my last post, this is kind of a lean year for Follicular Lymphoma at ASCO. There are far fewer presentations on FL than there have been in the recent past. And no "blockbusters" -- no major studies that are being presented with new information about new treatments that we haven't seen much of (though there is one that presents data for a new treatment that I will get to soon).

Instead, most of the the FL presentations at ASCO are about refinements -- new information about treatments we are already familiar with. In truth, that's what most ASCO (and ASH) presentations every year are about anyway, and that's not a bad thing. Clinical trials can only give us a certain amount of information, and after a treatment has been approved, there's still plenty we need to know about long-term effectiveness and side effects and "real world" factors. 

So while there isn't too much this year with a high "wow factor," there is some interesting stuff to talk about.

One study is called "The clinical trials landscape in follicular lymphoma: A systematic review." It looks at how clinical trials for FL treatments are conducted and the complications that come with a disease like ours.

Some background: a clinical trial is a way of systematically testing a treatment, and ideally allows us to compare treatments to one another by looking at effectiveness and safety. The problem comes in how effectiveness is measured.

In an ideal world, we would measure by Overall Survival, or OS. In other words, we look at how many people are still alive at the end of the trial, and if there are more alive than there were in a trial for a different treatment, then we know the new treatment is better. That seems like the best way to measure the effectiveness of a cancer treatment -- it keeps people alive.

The problem, at least for FL treatments, is that FL patients tend to live a long time. The median OS, as presented by the researchers who did this study, is "over 15 years." So more than half of FL patients will live for more than 15 years after diagnosis. That's great for us patients, but less great for those who are developing treatments.

The reason is practical. If researchers have to wait 15 or more years to accurately measure OS, that means it's going to be even longer before they can get approval for their treatment and start making money off of it. That's a legitimate concern. As much as I'd love people to develop treatments based only on their love of science and their genuine concern for cancer patients, the reality is that someone has to pay for all of that research, and they want there money back. If they have to wait 15-20 years, there is much less incentive for them to invest in the first place. That's the reality.

So researchers develop "surrogate endpoints." They try to find some other way of measuring effectiveness that won't take so long. So they can say to the FDA or other regulator, "Our surrogate endpoint is 5 year PFS. If someone is able to go for 5 years without the disease progressing, then we can assume they will have a long Overall Survival." It's not a perfect system.

This ASCO presentation looks at the different surrogate endpoints that researchers have been using in FL trials. It identified 28 phase III clinical trials involving FL. It found that 79% of the trials used Progression Free Survival as its primary endpoint, with 18% using Overall or Complete Response Rate. Other surrogate endpoints included Progression Of Disease within 24 months (POD24), Complete Response at 30 months (CR30), and Minimal Residual Disease (MRD). 

About 50% of the trials included some measurement of Quality of Life, which wouldn't count as an effectiveness measure, but it's definitely a good thing to look at.

Also, about 50% of the trials involved CAR-T or Bispecifics, which brings up the possibility that Overall Survival for FL patients may increase even more. Again, that's an excellent problem for us to have, but it is still a problem, in terms of research. The researchers call for more research into how effective surrogate endpoints are, and perhaps finding new ones that will do a better job.

So while it is frustrating to know that our clinical trial system needs some improvement, it's also good to know that the reason is we are living longer, a s group. For now, that seems like a pretty good trade-off, but moving toward a more perfect system should remain the goal.

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One last reminder:

Remember that I'll be one of the speakers the Follicular Lymphoma Foundation's webinar, "FL Treatment Options – What You Need to Know," taking place Thursday, June 5, at 12:30 Eastern Time.

You can read more about the webinar and register at this link: https://us02web.zoom.us/webinar/register/2617476619964/WN_S3L8Al8tQAOjPWBy6ERxCw#/registration

There will be a recording posted later if you can't make it (or you're seeing this too late).

Hope to see you there!

 

 

ASCO Review: Treatment Preferences in FL

It's finally time to get to some ASCO reviews.

As I said in my last post, there seems to be a much smaller number of presentations about Follicular Lymphoma this year than in the past. Not sure what that's all about. There's a major Lymphoma conference in a few weeks in Lugano, Swtzerland, and a smaller one in Texas pretty soon, so maybe researchers for those instead. I haven't seen any discussion of it online. Not a bad thing; I'm just curious.

So, as I have been promising, the first one I will look at is one that I have a co-author credit for: Abstract #11109, "Treatment preferences of patients, caregivers, and physicians in follicular lymphoma (FL): A global discrete-choice experiment (DCE) study." Authored by Mitchell Smith, Mei Xue, Erlene Seymour, Yan Meng, Julie Dodds, Todor Totev, Leah McAslan, Andrew McAslan, Robert McEachern, Paul Mollitt, Lilian Diaz, FengYi Jiang, Krysten Klein Brand (KKB), Dominic Pilon, and Keri Yang.

I don't want to misrepresent myself here. The presentation is a poster detailing the results of a survey of FL patients, their caregivers, and some oncologists. There were obviously many folks involved, and the doctors and statisticians and writers did most of the work. But there were three patients and one caregiver who added enough of our perspective on how to ask questions and what the answers meant that we earned co-author credit. Mostly, it's just really cool to see my name on an ASCO presentation abstract. 

As I said, this presentation give the results of a survey, and some of you may have taken part in it. Last November, I posted a link for the survey. If you took part, you probably remember, because it's kind of an unusual (but really interesting) way of asking people for preferences. It's called a "discrete choice experiment." In this type of survey, you are asked to make a series of choices between direct comparisons. So you might be asked if you preferred a treatment that might give you 5 years of remission, but with severe side effects, and would require 1 hour of travel? Or would you choose 2 years of remission, with mild side effects, and 3 hours of travel? The survey asks you to choose between the two. And then it gives you 10 more comparisons, with different years of remission, different side effects, and different travel times.

The idea is that you are being forced to make priorities. And those forced choices will show up as a pattern. Combine all of those choices and patterns from everyone who took the survey, and you can see larger patterns that tell you something about how patients, caregivers, and oncologists make choices about treatments.

Specifically, the survey asked questions about efficacy of treatment (how long the treatment would result in Progression-Free Survival), safety (the impact of side effects including fatigue, cytokine release syndrome (CRS), and nerve-related issues on quality of life), and convenience (the way the treatment is administered, how long the treatments take, and the time needed to travel to the treatment center). The choices aren't real treatments, just hypotheticals to get people to make a choice and create a pattern.

The survey was completed by a total of 337 patients, 37 caregivers, and 29 oncologists from 25 countries.

There were some interesting differences in the way the groups responded.

 Patients preferred treatments with a longer Progression Free Survival, mild or no impact of fatigue, CRS, and Nerve-related events. They preferred oral tablets over infusions. And they would rather have treatment twice per week for three months rater than ongoing treatment forever with a doctor's appointment every 3 months. And they'd prefer as short a travel time as possible.

All of that makes sense for patients. There's a kind of "let's get this over with" attitude that lots of us have. 

All three groups (patients, caregivers, and doctors) ranked PFS as most important. Again, this isn't very surprising. We all want our treatments to be effective for as long as possible.

But after that, there was a little bit of a difference. For patients and caregivers, the next most important thing was treatment convenience (oral tablets, less time in the doctor's office, and less travel time). But for the oncologists, the second most important thing was safety (less severe side effects). 

This makes sense, too, in many ways. The doctors who took the survey were mostly oncologists who saw patients and also did research. In a clinical trial, efficacy and safety are the most important things, so maybe that's what they are kind of trained to look at. For patients and caregivers, the treatment experience is about making it all as easy as possible, and getting it over with as quickly as possible, and moving on. 

That difference in preference should not be seen as oncologists not caring about patients' day-to-day lives. Quite the opposite. But they see that caring through a different lens. Quality of Life matters for all three groups; it's just playing out differently, based on lived experience.  

One last bit of statistical analysis that hit me hard:

"On average, patients were willing to accept reductions of 1 y of PFS for treatment requiring <30 min of travel vs >2 h, 0.7-1 y to receive treatments with less impact of AEs on QOL, 0.6 y for oral tablets vs blood collection and intravenous infusion, and 0.5 y for 3-mo treatment vs continuous duration."

As I said this is statistical analysis. No one was asked "You say you want 5 years of PFS. But how many months would you knock off that number if it meant you could take a pill instead of an infusion, or you'd have to travel for 30 minutes instead of 2 hours?" I don't think I could answer that question directly. I'm not sure any of us could. 

But that's what makes a discrete-choice experiment so interesting. By making choices, we create patterns, and someone looking carefully at those patterns can say "Reducing travel time means you'd be willing to need treatment again one year sooner than you otherwise would." It's fascinating to me.

The conclusion to the abstract is incredibly important: "Insights on differences between preferences highlight the importance of informed discussion and a balanced, individualized approach to treatment selection."

We al want the same thing, whether we are patients, caregivers, or doctors -- to knock out this cancer for as long as possible, and to do it as safely as possible while disrupting the patient's life as little as possible. But how much we value those things is going to be different for each of us. Having a conversation about it with our doctor is so very important, so everyone knows what is important when those decisions have to be made.

It was a great experience to be a part of developing and analyzing this survey, and I am appreciative of those who asked me. I hope I'm able to do something like this again in the future.

But for now, I'll keep reading and reviewing this year's ASCO presentations on FL. I'll have more for you soon.

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One more thing -- remember that I'll be one of the speakers the Follicular Lymphoma Foundation's webinar, "FL Treatment Options – What You Need to Know," taking place next Thursday, June 5, at 12:30 Eastern Time.

You can read more about the webinar and register at this link: https://us02web.zoom.us/webinar/register/2617476619964/WN_S3L8Al8tQAOjPWBy6ERxCw#/registration

Hope to see you there!

 

I'm Back! There's Work To Be Done!

I'm back again, and ready to write some more!

My wife and I just spent 10 days in Europe on a river cruise down the Rhine. A few days in the Netherlands, then Germany, France, and Switzerland. We saw many cool things, ate good food, and met interesting people. 

We've been trying to make travel a priority. We went to Italy a couple of years ago, and we starting planning our next big trip on our way home from this one. We were both lucky when we were much younger to have been able to travel, and that got harder after we had kids. Now our kids are grown, and we think about the health issues that both of us have. I'd be very sad if, one day when we're older, we looked back and say "Remember when we used to talk about traveling? That would have been nice." We don't want that to happen.

So we do what we can to make it all work. Traveling takes time, and money, and energy -- and there are times when it seems like we don't have much of any of those things. But we decided to prioritize these experiences.

To put this in cancer terms -- that's kind of what Survivorship is all about, isn't it? It's about making decisions that let us live the life that we want, on our own terms. So we'll keep driving our 12 year old car as long as we can. I'd rather drink a Kölsch in Cologne than impress the neighbors with a new CL55.

As I said, we met some wonderful people on our trip, especially a group of four from Pennsylvania, two couples who are lifelong friends. They truly made the trip something special. We enjoyed spending time with them.

And of course, as you get to know someone, there is almost always a cancer connection. It's hard to escape. One of our four new friends is a three-time cancer survivor. We shared stories -- of the awful things people have said to us about cancer, and of the importance of trying to laugh sometimes. But mostly we didn't talk about cancer. We drank wine and talked about our kids and won a trivia contest. Like I said -- survivorship. 

I hope you are all able to do the things that make you happy. It feels very good.

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I have been able to look at the ASCO abstracts for this year, and so far, I'm not seeing much about Follicular Lymphoma. I'll start reviewing them soon, including the one that I am a part of (I know I've been promising that -- I'll get to it very soon).

In the meantime, the Follicular Lymphoma Foundation has put out the official announcement for their webinar next week. Here's one of their social media posts:

 

 

I'll be one of the speakers for the webinar, which is happening next Thursday, June 5, at 12:30pm Eastern Time. I'll talk about my Follicular Lymphoma treatment experience. You'll also hear from Dr. Mitchell Smith, the Chief Medical Officer for the Follicular Lymphoma Foundation, and Prof. Andrew Davies, Professor of Haematological Oncology at University Hospital Southampton. They're both going to be fantastic. 

You can read more about the webinar and register at this link: https://us02web.zoom.us/webinar/register/2617476619964/WN_S3L8Al8tQAOjPWBy6ERxCw#/registration

If you have questions for any of the panelists, you can submit them on the registration form. 

And if you can't make it to the webinar, the FLF will post a recording on their website after it is over.

I'm really looking forward to it. The FLF is a great organization, and I'm honored that they have asked me to be a part of this. 

It's good to be back. More to come very soon.