ASCO: Exercise and Cancer

A reader left a comment on my last post that I want to address here, rather than in the comment section:

Thank you for ASCO coverage. Seems ASCO's headline grabber this year was the "Structured Exercise Program Improves Survival Outcomes in Patients With Stage III or High-Risk Stage II Colon Cancer" story. Do you think this study translates to FL folks, especially in terms of recurrence and survival? I just noticed current Mayo study along the same lines for indolent NHL lymphomas CLL and MZL. Any "there" there?

I have been reading about this presentation, and I was considering writing about it (especially since there is so little to write about Follicular Lymphoma this year. 

My quick take on it is this -- it's a study that describes a very specific research project, and was reported with some headlines that make it seem to affect many more people than it actually does. It is both excellent research and a good lesson in reading carefully.

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Let me start off with one of the headlines that describe this study (from NBCNews.com, which shouldn't be so clickbaity): "Exercise may benefit colon cancer patients as much as some drugs."

Now, clickbait is a headline that is meant to get you to click on it and visit the page. If I'm being fair, the title I'm using for this blog post is kind of clickbaity, but that's the point -- the title doesn't fully represent what the content of the article says, exactly. There were a lot of articles that did something similar, speaking in very general terms about the study to make it more attractive to readers. It's a very common tactic in popular science writing. The NBC News headline makes it sound like exercise is a substitute for more traditional cancer treatments for anyone with colon cancer.

That's not the case. Exercise didn't cure anyone's cancer.

But that's not to say it isn't an important study. From what I read, when the presentation was finished, the oncologists in attendance actually gave a standing ovation. So what the study actually says is still pretty important.

The presentation is #LBA3510 "A randomized phase III trial of the impact of a structured exercise program on disease-free survival (DFS) in stage 3 or high-risk stage 2 colon cancer: Canadian Cancer Trials Group (CCTG) CO.21 (CHALLENGE)."

The study looked at 889 patients with colon cancer from Canada and Australia, median age 61. About 90% of the patients had stage III colon cancer, and the other 10% had high risk stage II. The patients all had surgery followed by adjuvant chemotherapy (that is, chemo that was meant to "clean up" any remaining cancer).

It's worth repeating this, given the headlines -- all of the patients had surgery and chemotherapy. Traditional cancer treatments played a huge role in making them cancer-free. Exercise did not cure or prevent their cancer, at least in this particular study.

After chemotherapy, patients were split into two groups. The first group was given Health Education Materials (the abstract calls this the HEM group) that promoted good nutrition and exercise. The second group was given a Structured Exercise Program (they are the SEP group), supervised by a Physical Activity Consultant, who met with them twice each month for three years. The specific physical activity was chosen by the SEP patient. It could have been working out in a gym or it could have been just walking for 45 minutes per day. But it was structured, supervised, and done regularly. 

The results were fascinating. With a median follow-up of almost 8 years, 93 patients in the SEP group had their cancer come back, compared to 131 in the HEM group. After 5 years, the disease-free survival (DFS) was 80% for the SEP patients and 74% for the HEM patients. The 8 year Overall Survival was 90% for SEP and 83% for HEM.

This was a fairly large stage 3 clinical trial, not just observations or reports from patients, and that's what makes it so impressive. The patients in the trial reported in with their consultant every two weeks for 3 years. All of this is enough to make it pretty clear that the difference in the two groups with the physical activity that one group performed. Exercise didn't cure anyone's cancer, but it might have helped keep 90% of the patients alive for 8 years.

Now, I want to be clear about something else -- the reader who left the comment wasn't implying that exercise alone was a replacement for conventional treatment. The reader is clearly reading carefully, even referencing another Mayo Clinic trial on blood cancer. That reader is being careful.

That said, I don't know the answer to their question, Do you think this study translates to FL folks, especially in terms of recurrence and survival? I just noticed current Mayo study along the same lines for indolent NHL lymphomas CLL and MZL. Any "there" there?

This is a good time to once again remind everyone that I am not a medical doctor, and the best person to ask about treatment and lifestyle choices is your own oncologist. 

But I will say, for what it's worth, as a non-expert, I think exercise is an excellent idea, whether you are watching and waiting, in active treatment, or post-treatment. Moving our bodies is always a good thing. 

One of the great details from this study is the range of exercise that the participants engaged in, and the fact that it was their choice. I've heard it said that the best exercise that you can do is the one that you enjoy enough to keep on doing it. Sometimes when we think of a "structured exercise program,"  we imagine going to a gym and having a trainer yell at us as we push large amounts of weight. If that's what you enjoy, keep doing it. But if a 2 mile walk every morning is your thing (as it is with my wife and me), then keep that up. And if you have physical issues that make that harder, then find something else -- a shorter walk, or chair yoga, or water aerobics. But keep moving.

The best part of all of this was the enthusiastic reaction of the oncologists in attendance. I hope this means there will be follow-ups -- more rigorous studies on the benefits of exercise, whether it's post-treatment or during treatment. 

So I certainly hope there is some "there" there. We'll know for sure when the results of the Mayo trial get presented or published.

In the meantime, I encourage you to do two things:

1) Read carefully.

2) Keep moving.

More soon. 

 

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!