World Lymphoma Day

I've already written something about Lymphoma Awareness Month, and why awareness is both important and difficult. But today is World Lymphoma Awareness Day, as designated by the Lymphoma Coalition. 

The Lymphoma Coalition is a group of over 80 organizations from over 50 countries whose focus is on Lymphoma patients. It's an interesting group because they focus on so many different patients from different countries with different needs. Patients in the U.S., for example, may have access to more cutting-edge clinical trials than those in some other countries. But many in the U.S. may have a successful treatment only to find their lives devastated by financial toxicity, because they are responsible themselves for the cost of the treatment. We all have different issues related to where we live, and then we also all have the same issues that come from being a Lymphoma patient -- the physical effects of having cancer, and of the side effects of treatment, on top of the emotional effects that come with a diagnosis. The Lymphoma Coalition is concerned with all of it.

And so the theme of  World Lymphoma Day every year is broad enough to cover the needs of Lymphoma patients all over the world.

This year, the theme is We Can't Wait. It gets at the urgency that we all feel as patients.

If you go to the World Lymphoma Awareness Day website, you'll see that there are two particular things that the LC thinks are urgent.

First, we can't wait to address the ways the pandemic has affected people living with Lymphoma. I don't need to remind anyone reading this that the pandemic has affected us. Many of us have "imperfect immune systems" to some extent, whether it is outright being immunocompromised, or just having our immune systems work less efficiently, or just worrying about what might happen if our immune systems are challenged by viruses we don't know much about. It's been a difficult couple of years.

Second, we can't wait any longer to track lymphoma subtypes. I don't need to remind you all about my feelings on this. It's important for each of us to understand our own sub-type (the :C says there are over 80 of them). But it's important to normalize that, too, so news articles and informational essays don't lump all of those very different lymphomas into one. 

The World Lymphoma Awareness Day website has some sharable materials, if you're on social media and want others to know more. Feel free to go there and download them.

We're halfway through our special month. I hope you've become more aware of some things, and helped others to become aware.

But more importantly, I hope you've done something nice for yourself this month. Self-care is important, and if this is our month, you have an excuse. Get a massage. Get some ice cream. Take a nap. Do something to make yourself feel good. You deserve it. If you haven't yet, you still have a couple of weeks to do it.

Enjoy your day.

 

LRF Workshops

As you may know, lately I've become a fan of workshops put on by the Lymphoma Research Foundation. I think they are especially helpful for newly diagnosed patients, but great for all of us (including those who were diagnosed almost 15 years ago, like me). And best of all, they are free and done online.

The LRF offers a bunch of different types of educational programs -- "Ask the Doctor" sessions, workshops and webinars. But there are two that I think look especially promising and helpful that I want to highlight.

The first is the LRF Virtual Midwest Lymphoma Workshop. This one will take place on Saturday, September 24, and will feature speakers from some excellent cancer hospitals in the midwestern U.S. There are some general sessions about lymphoma, CAR-T, Covid-19 -- things like that which would appeal to all of us. But for me, the big attraction is that they break out and do a dozen different sessions for specific diseases, including two separate sessions on Follicular Lymphoma -- one for newly diagnosed patients and one for relapsed/refractory patents. To me, that's a sign that these folks know what they are doing. They recognize that there are very different needs for these groups.

There's also a session on Lymphoma Survivorship -- dealing with life after treatment. The speaker is Dr. Carrie Thompson. I've head her speak on this topic before -- she's fantastic. 

The other one is kind of similar: LRF's 27th Annual North American Educational Forum on Lymphoma, October 28-30. It's similar in that there are lots of the same topics, but it's a 3 day event, so there will be even more, and in more depth. One of the things I'm looking forward to with this event is that there is a little more time to discuss research (yes, I'm still a Cancer Nerd). There's lots of focus on providing basic information, and on living with specific types of lymphoma, including FL, but there's also time to get into things like immunotherapy, biomarker research, and oral therapies. A lot of that comes in breakout sessions, meaning there is a choice of 4 or 5 different topics, so you can't go to all at once. It will require some choosing. But it will be great anyway. Lots of excellent speakers at this one, too.

I hope some of you can find time to attend one or both of these events. And if not, I encourage you to keep an eye on the LRF events page for something else that might be useful.

Why Awareness Is Hard

Many of you have probably seen the recent news about the actress Jane Fonda. This weekend, she announced that she has been diagnosed with Non-Hodgkin's Lymphoma, and has begun chemotherapy, which she will be undergoing for six months.

First of all, and most importantly, I'm sure we all wish Jane Fonda an easy time with treatment, a successful outcome, and good health. We all know how it feels to hear those words, "You have cancer." And we all know how tough it is to deal with the day-to-day anxieties that come with a diagnosis and treatment. It's just not something anyone would (or should) wish on someone else.

Now, to be a little critical. As many of you know, I have a real pet peeve with people being "diagnosed with Non-Hodgkin's Lymphoma." I've read about 25 news article that describe Jane Fonda's announcement, and most also provide some background information about NHL. It's an attempt to be helpful. But to me, it's not as helpful as it could be.

Why? Because, in some sense, there is no such thing as "Non-Hodgkin's Lymphoma." Depending on who you ask, there are anywhere from 40 to 90 different types of NHL. Some are slow-growing, like Follicular Lymphoma,  where people can go years without needing treatment. But some types are very aggressive, like Burkett's Lymphoma, where lymph nodes can double in size with 24 hours. 

And some of the articles do make this distinction. But at the same time, they also mention statistics like the survival rate for NHL. That makes no sense to me -- how can you lump in the survival rate for FL with Burkett's or another aggressive lymphoma and have it mean anything? Who is that educating? 

Part of the issue, of course, is that Jane Fonda announced her disease as NHL, rather than as a specific subtype. And that's very common -- the actor Jeff Bridges did the same thing when he was diagnosed not too long ago. I can't be critical about either one of them -- they make the choices they make in dealing with the disease. We all make our choices, often in the same way. We aren't necessarily pubic figures, but we choose who to tell and how to tell them and how much information to give. People do things in the way that makes most sense to them, and they may not be the way I would do them. That's especially true in the days right after diagnosis, when everything is so new and scary and incomplete. I can't be critical.

But the larger lesson here is, this is Lymphoma Awareness month, and it's up to us to be aware. It's easy for someone else to read an article (whether it's about Jane Fonda or just about Lymphoma in general), and come away with an incomplete picture. It's up to us as patients to be aware of our own disease, and understand it well enough to use that information to help ourselves. For some (like me), that means knowing nearly every detail of the disease and its treatments, because for me, knowledge is power. But for others, that might mean knowing as little as possible, because all of that detail just creates more stress. Better to trust the oncologist to make the right decisions. And that's fine too. We make those decisions for ourselves.

But it also means that, for those of us who can, we pass along our knowledge and educate others -- we make others aware. 

From what I've read in her announcement, she seems very optimistic, and is not planning on letting the disease or her treatments keep her from doing the things that she finds important. That's another great lesson from all of this. Live your life.

Awareness is hard these days because there are so many sources of information, all competing for our attention. Some are great and helpful; some are horrible; many are incomplete. Being aware is a complex thing -- it's intellectual, but emotional, and social. Do what you can.

Lymphoma Awareness Month

It's September, and that means it's Lymphoma Awareness Month!

Hurray!

If you've been reading for a while, you now I have mixed feelings about this month. On the one hand, I am very much aware of Lymphoma -- I've been living with it for almost 15 years. I don't need a reminder tat the end of every summer.

On the other hand, cancer awareness months in general are not really for the people who have that cancer. It's more important that others become aware of them. And that's true for a couple of reasons. 

First, people need to be aware of cancers because it might help them avoid those cancers. I site like Know Your Nodes from Lymphoma Canada can help people understand what their lymph nodes are and what they are supposed to do. And that means they might know their nodes well enough to know when there is a problem. That knowledge may help them catch a cancer early enough to treat it.

Second, people need to be aware of cancers because it may help with raising money for research for certain cancers. In the U.S., there's no doubt that the cancer that people are most "aware" of is breast cancer, and people and businesses donate lots of money to help breast cancer patients and fund research. Whatever you feel about pink ribbons (and cancer patients of all kinds have some very strong feelings about them), we all know what they mean. That kind of awareness is very effective.

There's a third reason to want to raise awareness. It can help as patients understand that we're not alone.

I was in a meeting yesterday with some other cancer patients about a project we might all be working on in the future. It's always interesting to talk to other cancer patients. We have so many common experiences. We shared some information about our own cancers, and how people often misunderstand them. We talked about the stupid things people have said to us that were hurtful, and that people didn't realize were so hurtful. We talked about the kinds of things that cancer patients need. And even though we had four different cancers -- all very different cancers -- we realized how much we have in common. There's something about cancer that's just different from other diseases. 

So maybe that is the value of awareness months -- it gives us a chance to share with one another. There's great value in knowing that others have been through the same thing you have been through. The details might be a little different. But the experience is the same.

Maybe that's the best way to "celebrate" this month. Find a way to connect with other patients, Consider attending a workshop or program from a group like The Lymphoma Research Foundation. Join a support group, in person or online. Find a story about Lymphoma and comment on it and ask questions. It's not so much about becoming aware as it is about sharing that awareness.

I hope this is a good month for you. Maybe it gives you an opportunity to stop and reflect, and think more about where you are right now. And if that's hard, that's OK. We all have periods in our lives as cancer patients when we just can't think any more about being a patient. Hopefully, those moments pass, and we find some peace.

Happy Lymphoma Awareness Month.

Tumor Microenvironment in POD24

Well, the winners of the Social Health Awards were announced yesterday, and unfortunately I did not win either of the awards that I was a finalist for. That's fine -- it really was an honor to make it to the finals, and the winners of all 10 awards do really amazing work. So I'm happy for them. And I thank you all again for all of your support, during the awards nominations and over the last 14+ years. 

I'll keep doing what I do.

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

Very cool research from the Journal of Hematology and Oncology, getting us one step closer (we hope) to figuring out the mystery of POD24.

A little background first. POD24 (sometimes called EFS24) stands for Progression of Disease within 24 Months. It's the idea that, for Follicular Lymphoma patients who have recieved successful immunochemotherpay (like R-CHOP or B +R), if the disease returns within 24 months, their outcomes are worse than other FL patients. Some research published earlier this year suggests that the media 5 year survival for FL patients is about 90%, but for POD24 patients, it's about 50%.

Figuring out POD24 is a big priority in the Lymphoma community. There are so many unanswered questions about FL in general, and even more for POD24. There have been lots of attempts to find biomarkers for POD24 -- something in the cells or the genes -- that can help doctors identify POD24 patients early on and treat the disease aggressively.  Or, even better, create new treatments that will act on those biomarkers in some way.

The research published in JHO is the latest attempt at finding biomarkers. The article is called "Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry." It involves some pretty heavy science, but I think it's fascinating.

A lot of cancer research lately focuses on the "tumor microenvironment." Basically, this is research that works on the assumption that cancer cells don't just survive because of what is in the cell themselves. Instead, they rely on things happening on their micro-environment -- the area that is right around the cell. There must be something nearby that is protecting the cell in some way.

This research looks at the ways that the body's immune system protects FL cells. The body does produce abnormal cells from time to time, and typically, the immune system recognizes them as problematic, and takes care of them before they can become an issue. But sometimes, something happens that allows them to slip past the immune system and become a problem. That's what might happen with POD24, according to this research -- the immune stystem not only allows the FL cells to keep growing, but might play an active role in protecting the cells.

Our immune system is kind of amazing. It has lots of different layers, so certain cells kind of float around and take care of simple problems. If they can't handle a problem, a different set of immune cells comes in to help, and sends out signals to even more immune cells. And if they can't handle it, even more powerful immune cells come in to help. 

(Of course, there are downsides to all of this. Our body reacts to all of this immune activity in ways that can be problematic, too. Cytokine Release Syndrome, for example, is a potentially serious side effect of CAR-T therapy that happens when the immune system is over-activated.)

 As for the research in the article, the researchers found that the tumor microenvironment -- the area that surrounds the cancer cells -- created a barrier to the FL cells, so immune cells could not get to them. They did this by recruiting certain immune cells (regulatory T cells) and macrophages (very powerful immune cells). It is especially important that the cancer cells can control the regulatory T cells, since these are the immune cells that control (or regulate) how the body is going to respond to an immune problem. 

The researchers looked especially at proteins that were on the immune cells that were causing the problems, and identified which cells had certain proteins or were missing certain proteins. (If you're interested in the specifics, the article says:

"More FL-cells in the peri-follicular regions suffered CD8⁺T cells attacks under simultaneous protection of regulatory T cells (Tregs) and/or macrophages compared with that in the follicles irrespective of POD24. During POD24, increased CD163⁻ macrophages with PD-1 ligand upregulation and decreased CD8⁺T cells with upregulated LAG-3 expression around FL-cells were observed in the follicles.")

The details matter to researchers, because those are the potential targets for any new treatments. Immunotherapy is all about using the body's immune system to treat cancer, either by changing the immune cells to recognize cancer cells, or by changing cancer cells so the immune system can control them. The researchers in the article hope that identifying those specific cells, and the specific features on those cells, can eventually lead to treatments that can target them.   

And that's the other really important thing to remember about this research: it's still just taking place in a laboratory, looking at cells and not at whole, complete people. This is very early research. In fact, it is published as a letter to the editor, rather than a peer-reviewed article. In other words, the research hasn't been reviewed by other researchers yet to validate it.

So while it's valuable, it will be a long time before it leads to any new treatments.

Still, I think it's pretty fascinating research, and it tells us something about how researchers are thinking about Follicular Lymphoma, and especially about how to handle the POD24 problem. It really is a priority for researchers, and even though it only affects about 20% of FL patients, it's nice to hear that those who are having the most difficulty are getting the attention.

And any new knowledge about FL and what makes it incurable is bound to help all of us. 

Secondary Cancers in Follicular Lymphoma

On my last post, a reader asked if I could write about other malignancies in Follicular Lymphoma treatments. My guess is that the request came because, in discussing the updated results of a trial in my last post, I mentioned the rates of secondary malignancies in the patients in the study -- that is, how many patients developed new cancers besides FL.

I'm not surprised at the request. As I was writing that, I kind of made a mental note to look into that statistic a little more, but the original full article didn't get into a whole lot of detail. But I also know that writing a statistic like that without any context is a nice way to get some people worried. My apologies for that -- I know how worrisome statistics can be, and as I've said in the past, the times that my disease has worried me most have been because I've read some statistic and it got stuck in my head.

So I want to add some more context to that statement, and give a little more information from the past couple of years about secondary malignancies in FL.

But first, I'll remind everyone of something important -- I am not a medical doctor, or a cancer researcher, or a biologist. I'm just a cancer patient who reads a lot. If you have concerns about your disease, the best person to talk to is your doctor.

Now on to the recent research.

I actually wrote about this topic a few months ago, describing research done this year on secondary cancers in Non Hodgkin's Lymphomas, including FL. The research describes a study of patients with NHL in Sweden, looking at a large database of 30,000 patients that tracked how many of them developed a second cancer after treatment. The study compared the 30,000 NHL patients with another database of 30,000 who did not have NHL, and compared how many of them developed cancer over time. Doing this allowed the researchers to see how much more likely a lymphoma patient was to develop cancer than the general population. If a study just said "FL patients have a 12% chance of developing a secondary cancer," that might seem bad. But if the same study says everyone in the world has a 10% chance of developing cancer, then to me, that 12% doesn't seem quite so bad. 

You can read the original article in the link above, and read my (non-expert) commentary, but the conclusion comes down to a few things.

First, Lymphoma patients do have a higher risk of developing secondary cancers than the general population, according to this study. However, that risk also stayed steady over the years in the study (1993 to 2014), and actually decreased for some cancers or Follicular Lymphoma patients. The decrease seemed to come from more patients receiving treatments other than traditional chemotherapy (like CHOP or Bendamustine), which generally cause fewer secondary cancers. Let me explain that again: in the early years of this study, before Rituxan and other non-chemo treatments, FL patients were more likely to develop secondary cancers because they were more likely to receive chemo. As more non-chemo treatments become available (Ritixan and other monoclonal antibodies, R-Squared, Inhibitors, CAR-T and other immunotherapies), the chances of developing a secondary cancer become smaller.

Let's look at another study, this one from 2021 that looked at over 13,000 FL patients from the Netherlands. It's called "Risk of second primary malignancies in patients with follicular lymphoma: a population-based study in the Netherlands, 1989-2018." It's very similar to the study of FL patients in Sweden, and comes up with some very similar results.

The Swedish study found that 11% of FL patients eventually developed a secondary cancer, while the study from the Netherlands found that about 12% developed one. Patients were more likely to develop a secondary cancer the farther out from their diagnosis that they went. This makes sense -- in the general population, older people are more likely to develop cancer than younger people. 

The cancer most likely to be found? Squamous Cell Carcinoma of the skin. (Interestingly, William also commented on the last post, pointing out that his wife, an FL patient, has had several basal and squamous skin lesions removed. Thank you, William -- you're always on top of things, even before I ask.)

Other secondary cancers include myeloproliferative neoplasms (MPNs), and myelodysplastic syndromes (MDS), which can lead to leukemias (although the article from Sweden had good news about this for FL patients), and solid tumor cancers of the mouth, stomach, colon and rectum, and  kidney.

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

So what to make of all of this?

I think it's fair to say that secondary cancers are just unavoidable for a segment of the FL population -- a little over 10% of us. As the study from the Netherlands points out, our higher risk of secondary cancer comes from treatments like chemotherapy that can damage DNA and cause irregular cells to develop. But the fact that we have a cancer that affects our immune system is also an issue, according to those same researchers. Our bodies don't have as strong a response to factors that might cause cancer as others might have.

So what can we do about it?

Well, for me, I've always tried to be vigilant about how I feel. I see a dermatologist every year, who checks me for possible skin cancers. If skin cancers are the most common secondary cancer for FL patients, that seems like an easy one. I also get whatever regular screenings I'm supposed to get (just had a colonoscopy a few months ago, and I have an annual physical every year). I like to think that I am in tune with my body, and I know when something doesn't seem right. I don't take chances with my health, and if something is bothering me and a doctor dismisses it, I don't take No for an answer when I want it followed up. Self-awareness and self-advocacy won't stop cancers from happening, but they may help them get caught early, when they're more treatable.

As far as self-advocacy goes, I think it's very important to talk to your doctor about treatment options when the time comes for treatment. Bring up concerns about short-term side effects, but ask questions about long-term side effects too. If you have heart issues or a family history of hearty issues, that's worth mentioning. And if you have concerns about developing a secondary cancer, that should be discussed as well. Hopefully, your oncologist can give you information to ease your fears, or suggest another treatment that might be as effective. If not, try to get a second opinion from someone who does that for you. But also understand that sometimes the best treatment might be one that increases the chances of a secondary cancer. 

I also like this advice about secondary cancers from MD Anderson Cancer Center. To me, it puts things in perspective. Secondary cancers can develop for reasons that have nothing to do with cancer treatments -- some cancers are hereditary, for example. I try my best to not obsess about the decisions I have made.

I'd like to be able to end on a positive note, which is hard, but I'll go back to what I said about self-awareness and self-advocacy. Secondary cancers are not inevitable, but they do happen. Before treatment, ask questions about possible long-term side effects. Use that knowledge to be aware of your own body and possible changes to it, and be sure that any concerns you have are not dismissed. When a patient has a recurrence of FL, research shows that most of the time, the recurrence is found by the patient. Not by the doctor, or by a scan, or by a blood test. But because something didn't feel right to the patient.

So trust yourself and your ability to know your body.

And in the meantime, enjoy your life as best you can.

R-Squared Is Still Great

The Journal of Clinical Oncology has an update on the RELEVANCE trial. The very short summary is:  R-Squared is still great for Follicular Lymphoma.

Just as a reminder -- R-Squared is the name given to the combination of Rituxan and Lenalidomide (also known as Revlimid). The combination has already been approved by the FDA for FL patients who had already received another treatment. In short, the trials that led to the approval found that R-Squared was as effective as Rituxan + chemotherapy + Rituxan Maintenance. It was also considered more or less as safe as the chemo routine -- there were different side effects with R-Squared than with chemo, but not necessarily more dangerous side effects.

The approval was a big deal -- it showed that a non-chemotherapy treatment could be as effective as a chemotherapy. To me, that was a big deal in a sort of emotional sense, too. Many patients fear the word "chemotherapy" because they have probably seen its negative effects on family and friends. So to be able to tell a patient "this is NOT chemo" might make the emotional and psychological burden of cancer treatment just a tiny bit easier, at least for some people.

The article is called "Six-Year Results From RELEVANCE: Lenalidomide Plus Rituximab (R²) Versus Rituximab-Chemotherapy Followed by Rituximab Maintenance in Untreated Advanced Follicular Lymphoma," and it is an update on the trial that compared R-Squared to Chemotherapy in patients who had not yet been treated.

As the title suggests, this article reports on a six year follow-up of the 1030 patients in the trial (a pretty big number of patients). One important element of a treatment is durability -- sometimes a new treatment will take care of the cancer immediately, but then the cancer can come back in a matter of months. A six-year follow-up is a pretty good indicator of durability.

The results of the study showed that R-Squared remained just as effective after 6 years as it had been up to that point. The Progression-Free Survival (showing that the disease didn't get worse after 6 years) was 60% for R-Squared and 59% for R-chemo. Overall Survival was 89% for both groups. The transformation rate (the slow-growing FL turned into a fast-growing cancer) per year was 0.68% for R-Sqaured and 0.45% for R-chemo, and secondary primary malignancies (patients developed a new, different cancer) was 11% for R-Squared and 13% for R-chemo. There are some other statistical comparisons as well, but they all say the same thing -- R-Squared is as effective as R-chemo, and as safe.

The conclusion is pretty straightforward: R-Squared is a safe, effective alternative to chemotherapy for FL patients who have not yet been treated. 

This article is an update of a presentation made at ASH last December. Because it has been published, it is now considered peer-reviewed. That means the data has been checked by other experts. 

It's great news for us -- or for those of you who have not yet received treatment, anyway. R-Squared is not yet approved by the FDA as a first treatment for FL (it has only been approved for patients who have already had two other treatments). It will be interesting to see if this update leads to an FDA application for approval (though they don't seem to be in a big hurry). If so, that's one more option for FL patients.  

And that's good news.