Epcoritamab + R-Squared (+ Pharmacists)

In my quest for some Follicular Lymphoma-related reading material during this slow news time, I found an article in Pharmacy Times called "Epcoritamab Plus Lenalidomide and Rituximab in Practice: A Focus on EPCORE FL-1." 

As you can guess, Pharmacy Times is aimed at pharmacists, the folks who manage and sometimes advise on medications. That's the angle that makes it kind of interesting.

It's mostly a summary of the EPCORE FL-1 clinical trial results. EPCORE is the general name for a series of studies that have looked at the bispecific Epcoritamab. The EPCORE NHL-1 study looked at patients with several types of Non-Hodgkin's Lymphoma who were treated with just Epcoritamab. The EPCORE  FL-1 study is the one described here, and is the one that got people very very excited at last year's ASH conference.  This trial involves only FL patients, and combines Epcoritamab with R-Squared (Rituxan + Revlimid, also known as Lenalidomide).

The article provides a good overview of all of the successful trials for Epcoritamab, and especially for EPCORE FL-1. This was a phase 3 global study, with 488 patients from 30 countries. Patients had refractory or relapsed disease and had previously received a monoclonal antibody + chemotherapy. Patients were divided into two groups: one received R-squared and the other received R-squared plus Epcoritamab. 

Results were very positive. After a median follow-up of 14.8 months, The Epcoritamab group had a 95% Overall Response Rate (versus 79% for the R-squared only group). Most other measures were better in the Epcoritamab group did better than the R-squared only group -- including Progression Free Survival, Duration of Response, and Time to Next Treatment. It's easy to see why people were so excited at ASH.

Safety was also good, with low white blood cells counts (neutropenia) and infections being the most common side effects. Cytokine Release Syndrome, a major concern, occurred in 26% of patients, but all cases were manageable. Other side effects are described in the article. This isn't really providing any new data, just a summary of what was already reported.

What I found so interesting, though, were the "pharmacy" aspects of the article.

For instance, the article goes into some detail about dose escalation, something that gets mentioned in most oncology articles, but not in much detail.

In the EPCORE FL-1 trial, the dosing was changed partway through. At first, patients received a smaller dose first, and then a larger second dose. But in later studies, it was divided into three steps instead of two, so patients received it more gradually. Researchers think this probably helped lessen the severity of some side effects, including CRS. 

It also goes into some detail about "premedications" -- intravenous hydration, an antihistamine, an antipyretic (like acetaminophen), and corticosteroids (preferable dexamethasone) -- as well as "postmedications," including two to three liters of oral fluids within 24 hours after receiving Ecoritamab, plus corticosteroids (dexamethasone again) for 3 days.

I can picture an oncology pharamacist reading the results of the EPCORE FL-1 in an abstract, and thinking "That's nice, but what were the premedications?!" 

And I say that with great admiration, from one amateur Cancer Nerd to a professional one.

I don't really think about the role that pharmacists play in our treatment. 

When I had my Rituxan infusions, I had a blood draw first. Then I met with the oncologist to make sure everything was OK and I was well enough for the day's dose. Then I went to the treatment room, where the excellent Nurse Sue took care of me for a few hours. But somebody had to prepare the Rituxan. Somebody had to worry about my premedication hydration and the antihistamine I needed when I had an allergic reaction. 

It's kind of cool to think that there's someone else behind the scenes, keeping an eye on things. The size of our care team is really large.

I don't ever remember talking to a pharmacist when I needed treatment, but education is certainly a job for pharmacists, and the article discusses the role that pharmacists can play when a patient needs education about any of the medications that are a part of this treatment process. 

It's just kind of nice to have a broader perspective on things. It's one more person who cares about us, and who is looking out for us. We're lucky to have these hidden angels.  

Laughter Yoga

We're in that slow period now, as far as Lymphoma news goes. It's about six weeks until the ASCO conference, and I think researchers are holding on to all of their "good stuff" now, hoping they will make a big splash at that conference. But it's also too early for ASCO abstracts to come out, so there's nothing to read there.

What's a Cancer Nerd to do?

Go out and find something interesting, I guess.

I came across an article today about Laughter Yoga. It was emailed to me by a Public Relations group. I get lots of press releases about health issues from PR groups, and most of them have nothing to do with what I write about. I guess technically, this didn't have anything to do with it either -- not cancer or lymphoma. But I do take a yoga class once I week, and I certainly like to laugh, so I thought it was at least worth reading.

The email describes an article from the journal BMC Pediatrics called "Healing with laughter: the therapeutic power of laughter yoga in pediatric health – a systematic review."

The article describes research laughter yoga and its benefits for children. It's a review of several studies involving a total of 305 children who were taught laughter yoga.

So what is "laughter yoga"? It's a practice that combines laughter and playfulness with breathing exercises and mindfulness. It's not necessarily what many of us think of as yoga -- no downward facing dogs or warrior poses.  But it does focus on other things that are familiar to yoga practitioners, like mindfulness and breathing. 

I you would like to see Laughter Yoga in practice, here is a nice video from the Mayo Clinic. And this one from Celeste Greene reminds us to be playful for 5 minutes. No jokes -- just deliberate laughter. They made me laugh just watching them. But, honestly, I'm a very easy laugh. Ask my wife. 

The article collected data from studies about children, and it found some positive results. The children who practiced laughter yoga had a reduction in anxiety and stress levels. It did not seem to have an effect on clinical depression or self-esteem. But it did show an increase in Salivary Immunoglobulin A (SIgA), a measure of immunity. 

So there is definitely some good that comes from laughter yoga, at least for children.

I haven't looked into whether laughter yoga helps adults in the same way, but I can guess that it does. Laughter is a known stress relief, as is some deep breathing. It all kind of makes sense. 

So this is your reminder to stop every now and then and take a deep breath. And if you can, find something that makes you laugh. It might not help, but it certainly couldn't hurt.

In the meantime, I'll keep looking for any little gold nuggets of Follicular Lymphoma news that might be hiding out there.  

Take care of yourselves. 

 

Biomarkers for FL Relapse

The American Journal of Clinical Oncology published a very interesting article a couple of weeks ago that described research on biomarkers in Follicular Lymphoma. The article is called "Surveillance Strategies in Follicular Non-Hodgkin’s Lymphoma’s Using Molecular and Genetic Markers Improve Cost-efficiencies Over Routine Imaging Studies."

The idea behind the research is that we have a difficult time identifying patients who may transform or have POD24 (Progression of Disease within 24 months). Right now, about 80% of FL patients have good responses to treatment and then experience long survivals. But about 20% either transform or relapse after treatment within two years, and this 20% tends to have a shorter Overall Survival. 

The tools we now have to identify these folks are not very effective. They include things like FLIPI,the Follicular Lymphoma International Prognostic Index.  The FLIPI was never intended to be used as a tool to guess the likelihood of an individual patient's survival. If you take this little quiz, you'll see that it includes things like age, which is kind of useless -- thousands of people live long long lives with FL no matter what their age at diagnosis. The FLIPI index was developed many years ago, and has not been very effective in identifying that 20% of patients.

Over time, other prognostic models have been developed that look at factors that are a little bit more personal. For examples, the m7-FLIP which took the original FLIPI and added some possible biomarkers. This was an improvement, but still didn't completely identify that 20% as well as it was hoped. Too many of those high-risk FL patients were only identified after they transformed or relapsed within 24 months.

Other newer prognostic tools were developed in the years after that, like POD24-PI, PRIMA23, and ICA13. The authors of the article look at how effective they have been. Like m7-FLIPI, they do a good job, but not a perfect job, being anywhere from 43% to 86% effective.

The researchers looked at all of these models and essentially tried to find the best parts of them. Each prognostic model was developed from research tat looked for biomarkers, and those studies were all looking for (and finding) slightly different things. So looking at all of the data together might find some places that they overlap or that they do things that the others don't do.    

In the end, they came up with a model that they say is more comprehensive than the other models, and may do a better job of identifying high-risk patients as early as diagnosis. At this point, patients need to transform or relapse before they know for sure that they were in the high-risk group.  Identifying them early will allow doctors to possibly treat them more aggressively, and may in the future help to point researchers toward new targets for new treatments. 

The research team identified 10 biomarkers that seemed to only be present in high-risk FL patients. They did this by looking at data from patients who relapsed over a 14 year period. The biomarkers usually involve genetic mutations, which make them easier to identify.  

Of course, research like this is based on past results, so it's hard to know how effective it will be in actual patients at diagnosis. That's how these things often work -- it seems like it will be effective, but then they discover something else that their model hadn't picked up. And if that happens, that's OK -- that's how science works, and any step forward is great. But it does seem like this could be a step forward for a group that needs some help. 

I find it interesting that this study is being framed in financial terms. As the title says, a more effective model might "Improve Cost-efficiencies Over Routine Imaging Studies." In other words, a fairly simple genetic test that identifies a high-risk patient early on will mean fewer blood tests and scans and biopsies, and all the cost that goes with it. 

Lower costs are certainly important, and goodness knows that financial toxicity is a major problem for cancer patients. But all of the other benefits that come with improved prognostics matter even more  -- better Quality of Life, better mental health, and most importantly, improved Overall Survival. 

I'm hoping we see more data from this research in the next year or two as it gets applied to patients who are diagnosed now in the future.  I'll certainly be keeping an eye out.

 

When You Need to Take a Break

A long-time reader added a comment on my post about visiting the Grand Canyon last month. I always like to hear from people who have been reading for a while. 

This reader also pointed out that lately she has been stepping back from reading about Follicular Lymphoma. And that's good news, too.

It made me think about a message I got from a reader several years ago. I don't remember now if it was a comment or an email. But the reader apologized for not being in touch for the same reason as the recent commenter -- he was just not thinking about FL as much as he had.

I remember telling him that an apology wasn't necessary. It was an excellent thing that he had stepped back from reading and thinking so much about the disease.

This is one of several reasons why I don't monetize this blog. No advertisements. No subscriptions. No sponsors. No merchandise.  I know lots of health advocates who do those things, and I wish them luck. I know some of them have health issues that make it very hard for them to hold a full-time job, and the monetizing of their online accounts is an important source of income for them. I know I'm very fortunate to not have to be in that situation. 

But I also know that monetizing this blog would change things. A lot. For one thing, I'd be panicked every time I had a reader say that they were stepping back from reading so much about FL, and scrambling to figure out how to keep them. I don't want to have to put that much energy into this. I already put enough into it. 

It's always interesting to look at this blog's analytics -- the data that Google sends me about readers. To be clear, I don't receive any information about you as an individual. Unless you tell me who you are in a comment or an email, I have no idea who is reading the blog. 

But I do get information about how many people have accessed the blog every day, and I can see how many people from a particular country have read that day. (I've had readers from over 80 countries, which is really very cool to me.) So sometimes I will see a sudden spike in the number of readers from a particular country, and then maybe I'll get an email from someone in that country. I can make the connection -- that reader and maybe members of their family have gone back and read a few years' worth of entries. And then the activity from that country dies down. Maybe after a few weeks or months, I don't get much activity at all from them. 

I can see the rhythms of readership. Sometimes I get a whole lot of readers. Sometimes I don't get many. And then I get a lot again. 

And that's fine with me. When someone is newly diagnosed, they are looking for information. I'm happy that I can be a trusted source for them. Maybe I get lots of comments from them, maybe some emails. I welcome all of them. I love hearing from readers and I'm happy to help in any way I can, even if it's just listening to your story. (But I can't give out medical advice, because I'm not a doctor.)  

And that's the nature of this disease for many of us. It comes to us as a surprise, and it grows slowly enough that we can just not think about it much after a while. As much as I love to hear from readers, I also love to hear that someone has "graduated" and they don't think about me and the blog anymore. I don't take it personally. I recognize the rhythms.

For those of you who do drift away, go with my blessing. And if we've had some long communications by email in the past, but not in the present, know that I think about a lot of you and wonder how you are doing. I assume you're doing well. I'm tempted to email you sometimes to check in on you, but I also know that if you're in a good place, you probably don't need the reminder about the disease that you would get from me. 

So please drift away if you need to. I don't need the readership. I love having it, but I don't need it.

I plan on being here for a while.

Take care, everyone. 

 

Treatment Selection in R/R Follicular Lymphoma

The oncology website OncLive has another of their interesting video series on Follicular Lymphoma. They post these every few months -- a small panel of experts discussing issues related to FL. A lot of times, they discuss current treatments. I find it helpful to hear different Lymphoma specialists talk about how they handle particular situations, and explain their reasoning. 

The current video series is called "Optimizing Sequencing Strategies in R/R Follicular Lymphoma," though so far they only have one video posted. It's called "Navigating Treatment Selection in R/R Follicular Lymphoma," and as the title suggests, the Lymphoma experts talk about some of the factors that they consider when they are deciding on treatment for a patient who has Refractory or Relapsed disease (that is, the treatment they already had stopped working or didn't work at all).

The experts are Dr. Loretta Nastoupil from Southwest Oncology in Colorado, and Dr. Amitkumar Mehta from the University of Alabama - Birmingham. This is just the first part of a longer conversation, but they still had some good things to say.

Their focus here is on how they make decisions about which treatments to consider for a R/R FL patient. Dr. Nastoupil lists a few factors that she considers. She points out that FL is a very heterogeneous disease -- each patient is different. She says she sees patients in their 30s up to their 80s. Those groups will have very different goals. Some patients are extremely fit, with few comorbidities or other health issues to consider, which some are very frail. Some may have received single agent Rituxan (like me) while others had aggressive treatment that may have caused additional health issues. And of course, there is the issue of patient preference. Some patients want an aggressive treatment that gives them a chance at a very long remission. Others might prioritize a less aggressive treatment that does not affect their day-to-day lives as much but also is likely to mean treatment will be necessary within a few years. All of those factors make it hard say that there is an ideal second treatment.

Dr. Mehta briefly discusses the treatment landscape. He points out that two approved treatments have been pulled from the market for different reasons (PI3K inhibitors and Tazemetostat), but that some newer treatment regiments are also very promising. (He teases two of them, and says they will be discussing them later, probably in another video in the series. I assume they are Epcoritimab + R-squared and Tafasitamab + R-squared.) He says that in choosing a treatment, he tries to balance several factors -- how effective the treatment is, what kinds of side effects can be expected, and how those things  fit with a patient's individual goals. 

(I always like when Lymphoma experts make a priority of patient goals.) 

The rest of the series should be very good. It's not necessarily a presentation of anything new. That's usually how these video series work. It's more of  summary of where we are. I think that's really valuable, too.

One more thing that's worth pointing out. Dr. Mehta makes a comment about patient survival. He said when he was in training, they used to say that FL patients had a 10-15 year median survival. (He must be young. It was 8-10 years when I was diagnosed.) But he says that FL patients these days will probably have a "normal life span." Think about it. If the typical FL patient is 60-65 years old, and FL has a median Overall Survival of 20 years, that puts you right into the average lifespan of someone in the U.S.

And for you younger folks, remember that "median" means the midpoint. So if the median OS for FL is 20 years, that means half of FL patients will live longer than 20 years. I was diagnosed at 40. I fully expect to live to a normal life span. Dr. Mehta attributes this to having more and more effective treatments for R/R FL than we had in the past.

I've mentioned this before, and it's worth mentioning again.  Several years ago, I had a reader tell me that her oncologist said "If we can keep an FL patient alive for 5 years, we can keep them alive for 50." It's the same logic as Dr. Mehta's. The number of available treatments these days is so much greater than when I was diagnosed 18 years ago. We have options. And we have even more options being developed all the time.

That's what I like most about these videos. They give me hope. 

Lymph Nodes and Lymphoma

I don't usually write about stuff that's too "science-y." By that I mean the research that starts the process of trying to find a treatment. Sometimes I avoid it because it could be years before that research results in something useful (if it ever does). And sometimes it's because it's really hard to understand and trying to explain it would be difficult (for me and for you the reader).

But I read some Lymphoma research this morning that I think is fairly easy to explain, and which might actually be useful relatively soon.

A large group of researchers just published a piece in Nature Cancer called "Reprogramming of stroma-derived chemokine networks drives the loss of tissue organization in nodal B cell lymphoma."

The research is about the "architecture" of lymph nodes and how the nodes change with different types of Lymphoma. The researchers think that understanding those differences might help explain why some Lymphomas are slow-growing and some are fast-growing. And understanding those difference could lead to new treatments.

First some background. I think we all know what lymph nodes are. Many of us (though not all of us) became very familiar with them because they swelled up before we were diagnosed. And now every time we have any kind of bump or lump on our bodies we run to google to find out if there are lymph nodes in that part of our body. Lymph nodes are part of the immune system. They filter out bad things and help fight infections because they contain immune cells. When they are working well, they swell up. When they aren't working well, they stay swollen because there are too many immune cells -- a blood cancer.

The folks who did this research looked at the "architecture" of lymph nodes -- how they are divided up inside. Architects often design buildings with lots of apartments, so imagine a lymph node in that way. It's one structure with lots of apartments, and each apartment has its own separate family. So one apartment contains some B cells, a type of immune cell that is often called out first when there is an infection. (As you probably know, Follicular Lymphoma is a cancer of the B cells.) Another apartment contains some T cells. There are a bunch of different types of T cells, and they generally get called into action when the infection gets a little more serious. 

Now imagine there is a manager for this apartment building, someone who keeps the peace and make sure everyone is getting along. In the lymph nodes, this is what is called a Stromal Cell. These cells have a bunch of different jobs, but in the lymph nodes, they help keep everyone happy. They know that the B cell family in apartment 2A doesn't get along with the T cell family in 3B, so the Stromal cell makes sure they don't leave the apartment at the same time. When things are working well, this situation works out fine. The cells all get along, there's no cancer, and when there is an infection, the right apartment gets called on to do their job.

What the researchers found was that this same situation also happens when there is a slow-growing, indolent cancer like Follicular Lymphoma. The B Cells might have a bigger apartment in FL, but the architecture pretty much holds. Everyone does their job.

But when the cancer turns more aggressive, like with Diffuse Large B Cell Lymphoma, those walls don't hold. The Stromal Cells can't keep everyone in their apartment at the same time. It seems like that is where the problem begins. Imagine the apartment manager doesn't show up for work one day, or maybe had a few too many drinks the night before. He can't control all the cells in their separate apartments. 

What happens from there is a "vicious cycle." As T cells are called into action, they release pro-inflamatory signals. Basically, they start ringing the doorbells of other T cells and asking them to come out and play. And then those T cells start ringing the door bells of other T cells. Not only do they all come out and play, some of them stay inside and start knocking down the walls of the separate apartments. When this happens, it usually results in an aggressive Lymphoma like DLBCL. 

Wat the researchers found that is so important is that first, it's a problem with the Stromal Cell that seems to cause the bigger problems. And second, this loss of architecture isn't a result of the problem, it's the cause of the problem. 

My explanation is, of course, an oversimplification. The lymph nodes don't have actual walls dividing things. It's more like spaces where different cells hang out. But the comparison works -- when the apartment manager doesn't do its job, the building is a mess.     

Because the researchers seem to have targeted one cause of all of this, the Stromal cells, they are hoping that they can use that information to more accurately diagnose a patient, and then potentially find a treatment that targets the Stromal cell or some other part of the process that leads to the problem. 

It's very early research. It could be years before anything comes of it, if it ever happens at all.

But it's one more small piece of the puzzle that is Follicular Lymphoma. And that's something to be hopeful about.

Surviving in the Grand Canyon

I'm back!

You probably didn't even know I was gone, but I'm back from a week in Arizona, about 2500 miles from my home. My wife and I spent a week in Sedona, the Verde Valley, and the Grand Canyon. 

Anyone who has been to the Grand Canyon will tell you that words can't describe it and pictures can't capture it. But I'm going to give you a picture and share some thoughts anyway.

 

My wife and I had actually planned a trip to the Grand Canyon almost 30 years ago. I was going to Phoenix for work, and we had hoped to both go and spend a day or two at the Canyon. My wife was pregnant at the time with our oldest, and about a month before the trip, the doctor put her on bed rest because of a complication. Not only no travel, but no getting out of bed for more than a couple of minutes at a time. It was a very stressful few months. But mom and baby stayed healthy, and we had a beautiful baby boy. 

So now, almost 30 years later, we had the chance to try again, and we took that opportunity. We traveled with a group called Road Scholar. They aren't sponsoring the blog or anything, but I'm going to mention them because we've enjoyed our trips with them. They handle the details and make it easy for us to travel. We're at a point in our lives where we are happy to let someone else book our hotels, plan our meals, and do the driving. We just show up and enjoy ourselves.

As I said, words can't really describe something like the Grand Canyon, considered one of the seven natural wonders of the world.  And really, the details don't matter. But I will say that my wife and I spent a small amount of time on the Bright Angel Trail that goes down into the Canyon. We didn't go far -- less than a mile of the 16 mile trail. It was very hot and we were feeling the thin air. But we'd learned that less than 1% of the people who visit the Grand Canyon ever go below the rim. We felt like we had to have that experience.

Even going just a few hundred yards down the trail gives you a completely different perspective. You see things that you can't see from the rim. Your view is completely different. You become a part of something that 99% of the people around you are not a part of.

And for me, that's an important part of being a Cancer Survivor. 

My wife and I are getting older. And with age comes the usual slowing down. One or the other of us seem to have a new doctor or a new medication or a new diagnosis every six months or so. We're still reasonably healthy.  But we know that can change. We want to experience some things now while we can. For us, that means making travel a priority.

I mentioned the 30 year delay in seeing the Grand Canyon for a reason. I think lots of us put off doing things that we'd always wanted to do. For us, life got in the way. We had three kids, and dealt with everything that comes with having kids. They tend to take up your time, and your priorities change. And that's fine.

But then cancer comes along, and priorities shift again. There are so many more "what if" thoughts that come into our heads. Sure, I'd like to travel , but what if I pay for this trip to [insert your dream trip here] and the Follicular Lymphoma comes back? What if I feel awful while I'm traveling? What if I'm so worried about it all that I can't really enjoy myself?

We got tired of the "what if" thoughts and decided to just go with it anyway. There's always a "what if." We can't let that get in the way. Because there's one thing even worse that feeling unwell on a trip. It's looking back in 10 years and saying "I wish we would have done it anyway." If the Lymphoma isn't going to go away, we just pack it in the carry-on bag with the sunscreen and the granola bars. There's no sense in sitting at home staring at each other -- me, my wife, and the disease. It's coming with us. But we're all going.

Because that's what Survivorship is all about -- deciding how you will live your life after the diagnosis. 

You are the one who decides.

For us, we have decided that there's too much of the world we haven't seen, and we want to see it while we can.

Maybe you're not able to see the Grand Canyon, for whatever reason. You can't walk down from the rim and get a new perspective on the world. 

But I'll bet there's plenty of the world you haven't seen that's already all around you.

My wife tells the story of living just outside Washington DC. One year when she was in her 20s, her brother had returned home and the two of them went for a walk in downtown DC. They were walking near the Washington Monument when they realized that neither of them had ever been to the top of the monument in their whole lives, despite living 10 miles away. So they want to the top, and they saw the beautiful views of their hometown.

They didn't travel 2500 miles to do it. They traveled 10. And they changed their perspective and saw the world in a new way.

That's Survivorship. It doesn't have to take a lot.

I hope you'll do something fun today, maybe something you've put off for a while. I hope you'll do something to change your perspective on the world and your life. If you are able, I hope you'll start planning that trip you always wanted to take. 

You are the one who decides what your life will be after diagnosis. Don't worry about the disease. Bring it with you and have a great time.