Biomarkers in Stage 1 and 2 FL (plus, a chance to party!)

Interesting research this week from the International Journal of Molecular Sciences. An article describes research that may have found some biomarkers in patients with Stage 1 and 2 Follicular Lymphoma.

A little background. More than half of FL patients are diagnosed with stage 3 or 4 disease. Stage 1 and 2 certainly happen, but less often than advanced disease. Stage 1 in particular is located in on place, meaning it is easier to treat with traditional radiation. Some FL patients who receive radiation don't need further treatment, and some will eventually relapse.

The article is called "Proteomic Profiling of Limited-Stage Follicular Lymphoma Reveals Differentially Expressed Proteins Linked to Disease Progression Post-Radiation Therapy." It looks at a fairly small number of patients -- just 26 -- with stage 1 or stage 2 FL, who were treated with radiation. Nine of those patients experienced progression of disease, while the other 17 did not. With two groups to compare, the researchers used "high-throughput mass spectrometry-based proteomics" to examine biopsies from the 26 patients. Basiclaly, this is a method that helps researchers separate out and identify the different substances in a sample like a biopsy.

The process found a total of 1940 different proteins in the biopsy samples, with 78 of them showing up differently in the two groups. Researchers already know what function many of these proteins serve in the body. They may be part of the path of proteins and enzymes and genes that make a cell grow and keep it from dying when it is supposed to, resulting in cancer. Perhaps not surprisingly, the researchers found that proteins that do these things were not as present in the samples from the patients whose disease did not progress.

They found two particular proteins, CASP4 and CASP8, that seemed to correlate with shorter Progression-Free Survival. They point to other research that found the same proteins in advanced stage (stage 3 and 4) FL patients. 

They hope that further research will show that CASP4 and CASP8 are reliable biomarkers for predicting disease progression in FL. That will take some time to test out, but it would allow doctors to potentially recommend more effective treatments to individual patients.

This is a small study (26 patients) involving a limited population (FL patients with stage 1 or 2 disease that have received radiation), but it has larger implications. It's another attempt to identify biomarkers to help guide doctors and predict how a disease might behave. Identifying biomarkers seems to be more and more of a priority for the Lymphoma community lately -- they were brought up by Dr. Smith in the FLF's midyear report, and are important to the identification of potential FL subtypes, to give a couple of recent examples. It might not be that the community is paying more attention to it. It could be that there has been more success lately, and that's why we're seeing more about it.

Whatever the case, it's a cause for hope. 

******************

I want to make a quick mention of a Follicular Lymphoma-related event happening in November.

I know many of you are part of the Living with Follicular Lymphoma group on Facebook. It's a good group to be a part of, and I check in every day. It has almost 15,000 members from around the world. 

On November 11, they will be celebrating their 10th anniversary with a big party in London, sponsored by the Follicular Lymphoma Foundation. And everyone is invited. 

There is currently a poll being conducted in the Facebook group asking if people might be able to attend. If you are in the UK or nearby, or are just looking for an excuse to go to London, join the group and let them know so they have an idea of how big a party this will be.

Unfortunately, I cannot make it -- a tough time of year for me to travel. But if it had been at another time, I would have bought my plane ticket.

I can't tell you how incredibly valuable this experience is going to be for the people who are able to go. It is so very rare that we get to meet with people who have had the same experience with FL as we have had. There is something so uplifting about talking to someone who can smile and say "I know exactly how you feel!" and you know that they really do. If it's at all possible for you to be there in London, then try to be there. It will be a life-changing experience for you.

 Take care, everyone.

 

 

FLF's Midyear Research Update

The Follicular Lymphoma Foundation just published their mid-year update on Follicular Lymphoma Research. It's a fairly short document, and fairly easy to read (it's written by Dr. Mitchell Smith, the FLF's Chief Medical Officer, who always does a  good job of explaining things well).

Most importantly, it's very hopeful, pointing out the progress that's being made in FL research. 

I want to point out a few things that I found interesting, though I encourage you to read the report yourself.

First, I liked this line near the beginning: referring to the name of their symposium at the ICML conference in Switzerland this year, "Charting Our Progress Towards a Cure in FL," Dr. Smith says the title "reflects how the research community is increasingly convinced that FL will be curable -- the question is how and in what time frame."

That's a very hopeful thing to say!

I personally don't like to talk about cures for FL, because I've been dealing with it for over 17 years and I don't like to get my hopes up. The whole idea of a cure is complicated, given how hard it can be to measure a cure. But I do believe it will be considered curable one day, as the FLF report says, and it's very encouraging to hear that the Lymphoma community is feeling that same way. 

The report looks at three different types of research: from clinical trials that test out treatments; from translational developments that looks at biomarkers that might predict how a patient will react to treatment; and from biological research that identifies new information about how cancer cells stay alive and grow, which may open up new targets for treatments.

The clinical trials that Dr. Smith mentions are things like CAR-T and bispecifics. CAR-T is "maturing," meaning it's been around for a while so we're getting more information about how it works long-term. For example, about 50% of patients who were given one type of CAR-T remained progression free after 4 years, including about 45% who were POD24. That's great. I remember early research that had about 33% of CAR-T patients having a long-lasting response. It's improving.

Dr. Smith also points out that bispecifics don't have as much long-term data to look at, but what is there is encouraging, especially when they are combined with R-Squared. In general, there are more and more attempts at chemotherapy-free combinations, and more success with them.

One very interesting thing that he mentioned was the approval of Tafasitamab combined with R-Squared. The effectiveness is greater than most treatments currently available. However, he says, it might not be used quite as much as it could be because it requires "frequent hospital visits" and could be less effective than newer bispecifics like Epcotamab + R-squared. (As you may know, I've been thinking lately about how often Tafasitamab will be used and what might complicate that use.)

The clinical trial results are always the most interesting, because they are the easiest to understand and also the research that is closest to showing up in the doctor's office. But the more biology-based research is just as important, because they are the first steps in that clinical trial research. He mentions the research that has proposed three different subtypes of FL as well as research on the Tumor Microenvironment in FL (the stuff that surrounds the cancer cells, not just the cells themselves). 

He ends with another very hopeful quote about the state of FL research and the search for a cure:

 "It is clear the FL research community is moving from cautious optimism to genune confidence that cure is an attainable goal. By uniting scientific innovation, collaborative trials, and patient advocacy, we can accelerate the shift from managing FL as a chronic disease to eliminating it altogether. We are advancing faster than ever -- and with ongoing collaboration, the horizen for those living with FL grows ever more hopeful." 

Some excellent words to hang on to.

I encourage you to read the full report. You can find it here.

Stay hopeful, everyone.

 

Tai Chi and Qi Gong

I started a Tai Chi and Qi Gong class last night!

The exclamation point is there because I'm kind of excited about it. I've been fascinated by Tai Chi for a long time. My wife and I tried to do an online class a few years ago, and some of the moves were just too difficult to imitate when we could not have an instructor there to guide us. I finally gave in and signed up for an adult education class that meets on Monday nights. 

For those of you who aren't familiar with these things, Tai Chi began as a martial art, and it's easy to imagine some of the movements as blocking or parrying an opponent. But these days, it's mostly used as a health practice. It involves lots of slow, flowing movements, and it makes you very aware of your own body. Older folks are sometimes encouraged to try Tai Chi because it is fairly easy on the joints, and it helps improve balance.

Qi Gong is related, and even older. It also involves slow movements, deep breathing, and awareness of your own body. You can learn more about Tai Chi and Qi Gong and their health benefits at the National Center for Complementary and Integrative Health. And if anyone out there is a serious practitioner of one or both and explain things in better detail, please add to the comments.

The fact that they are often parts of Complementary and Integrative Medicine is certainly something that caught my attention. In fact, after the class was over, the instructor encouraged us to practice by watching videos that he had made for my cancer center's Integrative Medicine office. He does a lot of work with cancer patients in helping them find ways to move their bodies that are not too physically stressful. I didn't sign up for the class because of his cancer connection, though that was really nice to hear about.

 All of this reminded me of an article I had seen recently called "What are the optimal mind-body therapies for cancer-related pain? A network meta-analysis," published in the journal Translation Exercise Biomedicine. The authors looked at previous studies of mind-body therapies, practices like Tai Chi, Yoga, and guided meditation that help people become more aware of their bodies. They were interested in how those practices help cancer patients manage pain. The study found that Qi Gong and Tai Chi were best at helping patients manage pain. 

But perhaps more significantly, they found that many of the studies they looked at really didn't find much difference in the practices. All of them were effective in helping manage pain: Qi Gog, Tai Chi, Yoga, Baduanjin (a type of Qi Gong), Dance, conventional exercise, and health education.

I think the larger point is that some type of movement is helpful, and there are plenty of ways to exercise without going to a gym (Chair Yoga is becoming very popular, I know). It's a matter of finding the thing that speaks to you and trying them out until you find one that makes you feel good.

And really, it's about feeling good. I learned very quickly last night how little I use my shoulders these days. I had shoulder surgery about 10 years ago and can't do the type of weight lifting I used to enjoy. An hour of slow movement was enough to make me very aware of my shoulders. I wasn't ever in pain, but my arms got very tired very quickly. My legs were great -- my wife and I walk a couple of miles every morning. But my arms could use some work. I assume they will feel a little better every week. I know, at this point in my life, that bad things don't last forever.

All of this is, of course, related to Survivorship -- the way we live out lives after diagnosis and treatment. I want to be able to do the things I want to do, for a very long time. When my wife and I went on a river cruise earlier this summer,  we met some very active folks who were 10 or even 20 years older than us. We want to be like them and keep moving forward.

So I encourage you to find the things that get you moving ad make you feel good. It certainly doesn't have to be Tai Chi. That's my thing. Even my wife declines to join me in that -- she signed up for a yoga class instead. Which is good for her. 

Just keep moving forward.

Three Factors to Consider in Choosing R/R Treatment

The website Oncology News Central posted an interview a few days ago with Dr. Ahmit Mehta, a Lymphoma specialist at the University of Alabama at Birmingham. It's called "Three Factors to Consider in Relapsed/Refractory Follicular Lymphoma Care." It runs a s a video, but there is also a transcript if you'd rather read, or you need to translate. The website is mostly aimed at oncologists and other health professionals, but I have to say, Dr. Mehta does a fantastic job of explaining things very clearly. I don't know if anyone out there is a patient of his, but I'd bet he's just as good at explaining things in person. 

I thought it was an interesting interview for two reasons. 

First, it focuses a lot on Tafasitamab, which I talked about in my last post. So it's kind of a timely video that way.

Second, he discusses the factors that he considers when he needs to help a patient make a decision about treating Relapsed or Refractory Follicular Lymphoma. Let's look at that first, since it's the title of the video.

When he was asked how he makes decisions about treating R/R FL, he said, "When the patient relapses, at that time, there are multiple factors we consider for second-line treatment. Usually, the way I think in my mind, is: Patient-related factors are number one, disease-related factors are number two, and number three (that I’ve added recently) is center-related factors."

I find this really interesting. I've seen lots of general descriptions about the kinds of factors that go into those decisions, but never in quite this way.   

First, the patient-related factors. (It's nice that he puts patients first, and not surprising if you watch the whole video). These factors include things like comorbidities -- the other health problems that a patient might have. Certain problems will mean that particular treatments are not a good idea, since their side effects can be aggressive and create even more new health problems. Second are the disease-related factors. Is the patient POD24 or showing B symptoms? An aggressive relapse might mean a more aggressive treatment recommendation.

And third is "center-related" factors. I thought it was really interesting that he added this consideration recently. Not all treatment centers offer every treatment, and something like a bispecific or CAR-T are only offered at a limited number of centers. If a patient will have a hard time getting to a treatment center, or staying at the center for a couple of weeks to be evaluated, then a different treatment might be considered instead.

Now, any decent doctor would consider all of those factors as well, and I don't think Dr. Mehta came up with all of that on his own. But I do appreciate the way he breaks it down, and how he shows the things that he prioritizes. As we consider our own treatment choices, those same factors are what we should be thinking about, or at least be prepared to ask questions about. 

The second interesting thing that Dr. Mehta talked about was Tafasitamab. As I wrote about in my last post, there are lots of Lymphoma specialists who are very excited about the newly-approved combination of Tafasitamab and R-Squared (Rituxan + Revlimid). Dr. Mehta is one of those specialists. He sees very real possibilities for Tafa-R-squared, as he calls it, becoming a very popular choice for R/R FL.

One thing I thought was interesting was that he said R-Squared was currently the most popular second-line treatment for FL. I haven't seen evidence of that, though I'm also not someone whose job it is to know such a thing. But anecdotally, it seems to me that lots of FL patients are receiving R-CHOP or B-R, especially if they didn't receive chemo as a first line treatment, as well as CAR-T or bispecifics. I wonder sometimes if doctors who work in academic medical centers, where cutting-edge treatments are developed and tested, have a different perspective on things than doctors in community clinics, where old habits tend to rule. 

Or maybe Dr. Mehta is correct, and more and more doctors are using R-squared as a second treatment for R/R FL. And if that's true, then the jump to Tafasitamab shouldn't be hard. (But, as I said last time, I have my doubts, still.) 

Overall, it's a very good video, and those of us who have already had treatment would find it very interesting. The video is about 15 minutes long, and as I said, there's a transcript available as well.

I hope you get a chance to watch or read.

Tafasitamab: New Standard for R/R FL?

I've been seeing some discussion online lately about Tafasitamab, and its promise for treating Follicular Lymphoma. There are a few people who think it could become the standard treatment for Relapsed/Refractory FL, given the success of the clinical trial that led to is approval a couple of months ago.

But all of the positive talk got me thinking more about how certain treatments get to be so popular, and why others never really seem to catch on.

Part of my thinking this ways comes from a conversation I had recently with someone about RIT (RadioImmunoTherapy). This type of treatment involves taking a monoclonal antibody (something like Rituxan) and adding a tiny amount of radiation to it. Because the antibody seeks out a protein on the lymphoma cell, the radiation gets delivered right where it is needed, so there is less damage to cells that don't need the treatment. It was all the rage when I was first diagnosed, and I know a few people who received it many years ago and who a very long remission because of it.

However, it never really caught on the United States. The rules for a treatment like this required that an expert in nuclear medicine administer it, rather than a regular clinical oncologist. To be able administer it, the doctor would need 400 hours of training (if I am remembering this correctly). So very few people received RIT, even though trials showed it was very effective and there were a few different options available.

It's an example of a good treatment not getting to patients who would benefit from it.

So when I see the headlines about Tafasitamab -- that it might be a "game changer," or a "new horizon," or a "new standard," I have to wonder if it's really going to happen. (The "game changer" headline comes from a website that uses that phrase once a week about some new cancer treatment. The articles are generated by Artificial Intelligence. That's a whole different blog post.)

The reasons for excitement over Tafasitamab are pretty clear. In the InMIND trial, the phase 3 trial that led to its approval, 548 patients were either given R-Squared (Rituxan + Revlimid/Lenolidomide) or R-Squared plus Tafasitamab. The results were great. The Tafasitamab group had an 83.5% Overall Response Rate (versus 72.4% for the R-squared group) including a 49.4% Complete Response (versus 39.8%) and a median Progression Free Survival of 22.4 months (versus 13.9 months for R-Squared). Safety was comparable to R-Squared alone. You can find a good summary of all of the side effects here.

But here's why I'm a little skeptical about Tafasitamab becoming a new standard. One of the very enthusiastic pieces I saw about this said that this new combo would be a potential replacement for patients who would be eligible for R-Squared. This makes sense, given that it was shown to be more effective than R-squared. But how many patients would be given R-Squared in the first place?

About a year ago, the Follicular Lymphoma Foundation conducted a survey of FL patients from 49 different countries. One question asked which treatments the patient had received. In that survey, only 6.2% of respondents had received R-Squared. That's not a huge number. But if that's the ceiling -- if the Tafasitamab combination is going to replace it for some patients -- I'm not sure how much of a "game changer" it's going to be for patients in general.

I want to be clear about a couple of things. 

First, and most importantly, I'm not a doctor. I remind you all of that every now and then because it's really important for you to remember. I have not formal medical training. I'm not an oncologist or a cancer biologist (or a scientist of any kind). I'm a Cancer Nerd -- a patient who reads a lot, and then thinks and rights about what I read. So why listen to me? Good question. The most important person to listen to is your own doctor. 

Second, I want to be clear that I'm not anti-Tafasitamab in any way. Just the opposite. I hope it gets to the patients who would benefit from it. I still have a lot of frustration over RIT. I think it could have helped a lot of people 15 years ago, and it was frustrating t see it not being used. (Search for "RadioImmunoTherapy" on this blog and you can see my long history of frustrated posts.)

But take another look at the FLF survey. The treatment type that most patients have had? Chemotherapy, with 60%.  

And that's not necessarily bad (it can be very effective) and it's also explainable in some ways (FL patients can live for a very long time and treatment types were limited 15-20 years ago).

But I also think it's true that FL patients can be over-treated, given more aggressive treatments than necessary. (I'm getting this from a couple of conversations with oncologists.) People get chemo who don't need chemo, and maybe could do just as well with something like Rituxan.

So why so much chemo? I  read a comment from an oncologist once that doctors are creatures of habit. If they have always recommended chemotherapy, and it has worked well, there's not much reason to change to something else. It's hard to argue with that logic. As a patient, if my doctor said "My previous patients have done really well with Bendamustine," I probably wouldn't argue.

But I think that's ultimately what this is all about. Very few of us patients argue.

And I don't really mean "argue," as in getting mad at the doctor. I mean, few of us know enough to have a conversation with a doctor that might lead to a different option. Why chemo? What are the other alternatives? Why not them? Can you recommend someone else I can talk to for a second opinion? 

It's not really about arguing so much as asking questions. And that can be hard to do when you've just been told you have cancer. 

But it's what I hope you will do, especially with Relapsed/Refractory FL, when we've had some time to think and learn and perhaps plan. We don't all have the opportunity to get a second opinion, or to question the decisions that a doctor or a health plan make for us. But if we can? That's how change comes, and how good treatments get to people who need them.

Stay informed, and stay well.

 

Happy Lymphoma Awareness Month!

September is Lymphoma awareness month. 

It's Blood Cancer Awareness month, so it's also Leukemia and Myeloma Awareness Month, too. But I think most of us are concerned with Lymphoma, so we'll stick with that.

I always struggle with the idea of "awareness" at this time of year. Like most of you, I'm very aware of Lymphoma -- my own, and of the disease in general. But this month isn't really for us. It's about helping others be more aware of it.

Part of that is encouraging others to be aware of their own bodies. That's a big part of cancer detection -- knowing when something is wrong and then getting it checked out. Lymphoma Canada has a "Know Your Nodes" quiz that's very informative. Take it yourself and encourage others to take it, too.

And if you're comfortable, share your story. You can do that with the people you know, or share it on social media, if that's something you take part in. Or you can share it through the Follicular Lymphoma Foundation's website. 

I think that's very important. There was a time, not too long ago, when people wouldn't even say the word "cancer." It made cancer seem like a shameful thing. That led to all kinds of problems -- people not going to the doctor even if they suspected something was wrong. Isolation after diagnosis and during treatment -- exactly the time when patients needed others. And then the weird gilt that so many of us feel. Silence isn't good, at least in general. But as I said, share your story if you're comfortable doing so. There's no sense in making yourself feel worse by doing something you don't want to do.

And, of course, continue to educate yourself. Learn all you can about the disease. Not everyone wants to do this, and I understand that, too. I had an oncologist who told me that some patients didn't ever want to hear anything about the disease -- just did everything the doctor said. I get that, too. I had a loved one with cancer (not a blood cancer) who just couldn't stand the idea of doing any kind of research, for lots of reasons. But if you're here reading this, you're probably someone who likes to be informed. So keep that up -- keep finding good sources of information about FL and learning what you can. I'm always happy to share what I know on this blog, and to help people be informed, but remember that I'm not a doctor, and the best source of information is your own oncologist.

Still, there's much that we can teach one another, so I always recommend listening to other patients who can provide good information. 

I recommend The FL Community Podcast, which I wrote about last month. Their latest episode is available now. The hosts focus on Managing Treatment Side Effects in this episode, discussing common FL treatments and the typical side effects that come along with each. Nicky, one of the hosts, is a clinical nutritionist, specializing in oncology patients, so she offers some tips on eating well to manage particular side effects. This is a great example of what I mean about awareness -- well-informed patients telling stories and offering advice based on real experience. It's the kind of information that we often forget about when we are planning for future treatments. 

I hope everyone has a great month. Do something extra to increase your own awareness, and to share your knowledge with others. And be sure to do something to treat yourself -- a walk in a favorite place, or a meal that makes you happy, or a day off from work -- something that brings you joy. You deserve it.

Stay well.