Tazemetostat: Official FDA Alert

The big news in my inbox this week was the official FDA Alert for Tazemetostat. 

Tazemetostat had been voluntarily pulled from the market a couple of months ago by its manufacturer after results from a trial showed that there were concerns about patients developing new cancers. The news from the FDA gives more detail about that.

Tazemetostat had been given accelerated approval by the FDA, based on results from a phase 2 trial. It is an EZH2 Inhibitor, meaning it stops or inhibits an enzyme called EZH2, controlled by the EZH2 gene, which is part of process in calls that keeps them from dying as they normally would. About 20% of Follicular Lymphoma patients are effected by this issue with EZH2, and Tazemetostat was the first treatment that specifically targeted EZH2. That was enough to have the FDA give accelerated approval, which means patients could start taking Tazemetostat outside of a trial while the larger phase 3 trial went on to confirm the results of the phase 2 trial. 

But even  when they grated accelerated approval, the FDA was aware of potential issues with secondary cancers. About 1.7% of patients in the trial had developed a new cancer.

The FDA's alert gets into more detail about this. During the phase 3 trial, the rate of new cancers went much higher, with 18 of 318 patients (about 5.7%) developing new cancers, some as soon as 7.5 months after they began treatment, though most developed them 1-3 years after beginning treatment. 

Most of the new cancwrs were Myelodysplastic Syndrome and Acute Myeloid Leukemia, though there were some other blood cancers as well. 

The phase 3 trial isn't taking new patients, but it will remain open so doctors can follow up on long-term side effects of the patients in the trial.

Obviously, there is lots of bad news all around, but most especially for the patients in the trial who developed new cancers. The rest of the patients in the trial will also have to deal with the uncertainty of long-term side effects. And the rest of us have one less treatment to rely on.

The good news, if we can still see good news, is that things were handled as well as they could be, with the trial sponsors shutting it down as soon as they could, and then making sure they are following up with the patients in the trial and making sure they are taken care of. Let's all hope they are doing OK.

I think it's very important to state, though, that this doesn't mean we shouldn't take part in clinical trials. 

It's a natural reaction to read something like this and get nervous about serious side effects. But that's going to be the case no matter what treatment we end up taking. It's worth a conversation with your oncologist about whether or not a trial is right for your situation. I talk about trials with my oncologist at least every other visit, so I know what 's available.

Trials are the only way new treatments can become available. There is no other way. I remember very early on, soon after I had been diagnosed, someone in the online support group that I belonged to said that patients who agreed to be a part of a clinical trial are "heroes." I agree. 

If you are still concerned about clinical trials, or even if you just have questions about them, the Follicular Lymphoma Foundation has a webinar coming up on Tuesday, May 26, called "What No-one tells you about clinical trials and why it matters for your care."  It's going to be an excellent webinar. Click on the link to read more about it and register. 

More coming soon. Those ASCO abstracts must be just about ripe. 

 

R-Squared: 10 Year Follow-Up

The medical journal Blood published the results of a 10 year follow-up of R-Squared. The results aren't surprising (they are positive), but it's the larger content that it more interesting to me.

The article is called "Lenalidomide plus rituximab for previously untreated advanced follicular lymphoma: the 10-year RELEVANCE trial analysis."  As a reminder: R-squared is the shirt name for the combination of Rituxan and Revlimid (also known as Lenalidomide). R-squared was the first non-chemotherapy treatment that was shown to be as effective as traditional immunochemotherapy (like R-CHOP or R-Bendamustine), though it had a different set of side effects that were just as serious. The AUGMENT trial and the MAGNIFY trial led to R-Squared being approved for FL patients who had already received treatment. 

The RELEVANCE trial involved patients who had yet not received any treatment.  The original trial was large -- 1030 patients. More importantly, it is a two-arm study, so it shows a direct comparison between patient receiving R-Squared and those receiving immunochemotherapy. In 2022, I wrote about a 6 year follow-up study.  As I said then, "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-Squared 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."

So would R-Squared hold up as well after 10 years? Yes it does.

The median Progression Free Survival after 10 years was 110.6 months for the R-Squared group and 102.8 months for the Immunochemotherapy group.  The rate of patients with a 10 year PFS was 46.4% for R-Squared and 46.6% for chemo. Almost identical. The median Overall Survival and the median Time to Next Treatment were not yet reached in either group. (Remember that the "median" means the middle of a group, so if the median wasn't reached, it means that more than half of the group has survived and has not yet needed treatment after 10 years). The 10 year Overall Survival rate was 82.4% for the R-Squared group and 81.1% for the chemo group. The 10 year Time to Next Treatment rates were 62.2% and 66.3%. Only 9 cases of transformation occurred (3 with R-Squared and 6 with chemo). 

Comparing the 6 year follow and the 10 year follow up, it's not surprising that numbers went down after 4 more years, but more importantly, the numbers comparing the two treatments were very similar. As the researchers say, R-Squared continues to be an alternative to immunochemotherapy for untreated FL patients.  

The researchers also said this was 10 year follow-up was always part of the plan for the study, and that it would be their final analysis.

Here's what I mean when I say it's interesting in a larger context.

A few months ago, researchers published a 15 year follow-up of R-CHOP and used some statistical analysis to show that about 40% of patients in the study were probably cured. One of the big outcomes of that article was the idea that we now have a new benchmark -- other long-term studies are going to be challenged to do the same kind of statistical analysis to determine what their cure rate was. In other words, the RELEVANCE study shows that after 10 years, there isn't a whole lot of difference between R-Squared and immunochemotherapy, in terms of effectiveness. But can R-Squared match the 40% cure?

We're not getting that information here (or in the 15 year follow-up of R-Squared in the MDACC trial that was published in February) because that wasn't part of their plan. I don't know enough about statistical analysis of clinical trials to know if a biostatistician can come in later on and look at the data for a trial and make that same kind of call. But it will be really interesting to see if that kind of analysis starts showing up at conferences like ASCO and ASH and in medical journals. I'm certainly all in favor of it. I have a complicated relationship with the word "cure" after 18 years, but more studies that use that analysis and use that word might change my mind.

In the meantime, though, it's great to see long-term data of any kind to show that we have some choices. Given our own individual circumstances, there's more than one treatment available for us that will give us a chance at a good, long Overall Survival. That's some very happy news.

Odronextamab Versus the Real World

The medical journal Leukemia and Lymphoma recently published an article about the bispecific Odronextamab called "Comparative effectiveness of odronextamab monotherapy versus real-world systemic therapies in R/R follicular lymphoma." It says good things about Odronextamab, though it's the methods for the research that I find most interesting.

Odronextamab is a bispecific. If you need a reminder, bispecifics are kind of like monoclonal antibodies like Rituxan, in that they seek out a protein (CD20) on a cancer cell. But a bispecific also seeks out a protein (CD3 for Odronextamab) on a T cell (an immune cell). So it attaches to the cancer cell on ne end, and on the immune cell that can eliminate it on the other end. Bispecifics are one of those newer treatments that oncologists get very excited about (including my own oncologist). 

Odronextamab was approved for use in Europe in 2024, though it has not yet been approved for use in the United States. 

The study described in this article is interesting because of its methodology - the way it gathers and analyzes data.  

Some more background: Clinical trials are considered most effective when they are randomized, two-arm studies. What this means is, the people running the trial will decide on criteria for the trial (which previous treatments the trial participants have received, or maybe certain health conditions). The idea is to make sure that everyone in the trial is as alike as possible, so they can be compared to one another easily. As patients sign up for the trial, they are randomly placed into two groups (the two "arms" of the study). One group receives the new treatment that is being tested. The other group receives the "standard of care" -- the treatment that they would have probably received if there was no trial, a treatment that is accepted as being the most effective available. (In Follicular Lymphoma, that's complicated, because there a whole bunch of treatments that are effective for different patients.) But the idea is, you have two groups of very similar patients, receiving two different treatments, so they can be compared easily. It's the best way to argue that one treatment is better than another.

But randomized, two-arm studies are large and expensive and take lots of time. So some clinical trials are one-arm studies instead -- everyone gets the new treatment.But then when it comes time to argue that this new treatment is better than the others, it's harder to do so, because there isn't a group already set to compare it to. So the researchers have to find a study that is kind of close, that was done sometime in the past, and compare it to that study. The problem is, it won't be an exact comparison, because unlike a two-arm study, that older study might have had different criteria. One-arm studies like this aren't considered as reliable (though there are plenty of approvals of new treatments based on one-arm studies, especially accelerated approvals).

The study in this article did something a little bit different. Instead of comparing the results of an Odronextamab trial (ELM-2, which looked at 128 patients with Relapsed/Refractory FL), it kind of created its own second arm.  The researchers looked through electronic records to find patients who were treated at cancer centers similar to those in the ELM-2 study, who were R/R, and who were "real world," meaning they weren't part of another clinical trial. "Real world" research like this is less restrictive -- no criteria that exclude certain patients. 

A small digression to help explain things. Are any of you baseball fans who love statistics?  There's a baseball statistic called WAR, or Wins Above Replacement. It looks at a whole lot of statistics for an individual player, and then compares them to the average statistics for a player who would replace them if they had to leave the team. So WAR says "This player is valuable, because if he wasn't on the team and someone else was, the team would have lost 5 more games per year." It's all very theoretical, based on statistics. But it tries to show how things would be different under different circumstances.

This study seems to do the same thing. It's saying "Odronextamab is valuable because if it was available instead of these other treatments, this is how many more patients would have been successfully treated."

The "real world" patients' records were put together in something called the FLORA study. There were 88 patients who had received a total of 100 lines of treatment. Remember, these patients weren't part of a two-arm study, they were just regular FL patients whose records were examined years after they received treatment, which they received between 2015 and 2020. They received a wide range of treatments, mostly chemotherapy and immuno-chemotherapy, but also monoclonal antibodies, BCL-2 inhibitors, Stemm Cell Transplants, radiation, and some others. 

The researchers found that, compared to the real world group, patients in the Odronextamab study did better. The Overall Response Rate was 80.5% for Odronextamab vs 52.7% for the real world group. The Complete Response Rate was 73.4% vs 33.6%. Median Progression Free Survival was 20.7 months vs 11.5 months. Time to Next Treatment was 40.4 months vs. 9.7 months. 

The researchers recognzie that there are limitations with this research. For one thing, because it looks at patients from 2015 to 2020, it doesn't include any patients who received newer treatments like CAR-T or the other bispecifics that are now available. That might make things turn out differently. And, of course, because they are "real world" patients, they may have had health issues that would have made them ineligible for the ELM-2 trial. It's not really a fair comparison.

But the main ideas are still there. Odronextamab is an effective treatment for many patients, and safe enough to have already received European approval. And just like the theoretical statistical "Wins Above Replacement" in baseball, it's possible that some of the patients in the FLORA study would have had better outcomes with Odronextamab.

It's a very interesting study. I don't think it would hold up as a way to win FDA approval, but it does illustrate how effective Odronextamab is, and how great a need there is for more effective treatments for R/R FL.

I'm still looking out for news about Odronextamab being approved by the FDA. Maybe we'll get some updated news at ASCO in a few weeks.

 

CAR-T: Behind the Scenes

Fierce Pharma published a story a few days ago about Kite Pharma, the makers of the CAR-T treatment Yescarta, also known as Axicabtagene ciloleucel or Axi-cel. It's one of the three different types of CAR-T treatments that are approved for use on Follicular Lymphoma patients. (The others are Liso-cel or Breyanzi, and Tisa-cel or Kymriah). I know I often write about CAR-T as if it was just one thing, but it's a class of treatments, with a bunch of different options, not just one treatment. It's like referring to "chemotherapy" when there are a bunch of different specific types of chemo. 

The story reports on an interview with Kite's Senior Vice President in charge of technical operations. I'm not suggesting Yescarta is a better version of CAR-T than the others (I have no idea which is best, and it probably depends a lot on each patient's situation). But I thought some of the behind-the-scenes information was really interesting, and gives some hope for CAR-T maybe being more widely available. 

If you're new to the world of FL, or in case you just need a reminder, CAR-T stands for Chimeric Antigen Receptor T-Cells. If you know your Greek Mythology, you know a Chimera is a monster made of parts of different animals (a lion, a goat, a snake, and a dragon). A Chimeric Antigen Receptor T-Cell is also made up of different parts.  

The Kite website has a cool short video on the process. Basically, T cells are removed from the patient. T cells are immune cells, so their job is to find and eliminate invaders like viruses. They can't find and eliminate cancer cells, though, because cancer cells are not "invaders" -- they are our own cells that won't die like they are supposed to. So the T cells that were removed from the patient are taken to a laboratory where they are changed by adding a CAR gene. The CAR gene helps the cells create a receptor -- a little spike on the surface of the immune cell. Normally, T cells have receptors that allow them to attach to antigens on the surface of the invader. The CAR gene creates a receptor that lets them do the same thing to a cancer cell. They find the antigen on the cancer cell and attach to it and eliminate it.

So after the T cells are changed in this way, they are grown in the lab so they multiply. They are then shipped back to the hospital and infused back into the patient. This whole process can take 3 to 4 weeks. Once they are back in the patient, hopefully they will work as intended. And the great thing about T cells is their memory. Months or years after they encounter a virus (or a cancer cell), they will remember the antigen and send a signal to the body to create more T cells with that receptor. So when CAR-T works, it can work for a long time from just that one dose.

CAR-T treatments are exciting, but they have some downsides. For one thing, they don't always work, either in the short term or the long term. When they were first approved, they were described as being unsuccessful about 33% of patients, successful for about a year for 33% of patients, and successful long term for about 33% of patients.  Those numbers have gotten better as CAR-T treatments have been developed, but they still certainly are not perfect. 

Another issue is the potential side effects, like Cytokine Release Syndrome, or CRS. Cytokines are basically those proteins that signal the body to make more T cells when an invader is discovered. But too aggressive a response from the immune system all at once can create unintended problems, even death. This was more of an issue when CAR-T was first introduced, but doctors have done a much better job of recognizing it and managing early on. (And CRS is an issue with lots of immunotherapies, including bispecifics.) 

One of the biggest issues, though, is the cost. Because this is a bespoke treatment -- the T cells can only be used for one patient -- CAR-T can cost up to $500,000 per dose. It's a one-time cost, and some studies have shown that a successful CAR-T treatment can actually end up being less expensive than three or four unsuccessful courses of other treatments like chemotherapy. But it's still a lot more than most health insurers or health systems are willing to pay when cheaper options are available. That seems to limit its use.  

Back to the behind-the-scenes article. Another issue with CAR-T has been in the manufacturing process. It's a tricky thing. The T cells have to be stored properly and then shipped to a specialized facility. Ideally, there would be lots of those facilities so the cells wouldn't have to travel too far, and there could be lots of patients helped all at once. But that takes some time and money, and without a large group of patients paying for it, the building was slow (for all of the companies that have a CAR-T treatment). 

Apart from buildings for laboratories, the CAR-T companies also dealt with the supply of viral vectors. These are viruses that are used to carry the genetic material to the T cells. Viruses survive by getting int healthy cells and then multiplying. Viral vectors are viruses that have been changed so they won't do harm, but will carry the new gene material to the cells. But they needed to be produced, too. The CAR-T manufacturers have been improving all of those processes. 

These are some of these behind-the-scenes issues that are described in the article. I think we forget everything that needs to happen to actually make a treatment. We see it in a bag on an IV stand, but it went through a lot to get there. 

The last issue that is discussed in the article is to me the most exciting. CAR-T manufacturers are working on "in vivo" versions of CAR-T. Right now, CAR-T treatments are "ex vivo," meaning "outside the living body." T cells are removed from the body and shipped somewhere else to be changed into a form that can treat cancer. And this all adds to the cost.

But an "in vivo" version -- "in the living body" -- is one where the CAR genes are put into the patient, where they can find the T cells and change them. This is a whole lot harder. "Ex vivo" T cells are isolated in a container, all by themselves. "In vivo" T cells are floating around in the bloodstream with lots of other cells, so the "in vivo" process needs to find them first, and then go through everything that happens now in a laboratory.  That's a big challenge.

But if they can overcome that challenge, it might change the game in big ways. The process would be much less expensive -- the patient is the laboratory. 

That's not going to happen anytime soon -- the interview mentions this process happening "over the next decade." But it would be a huge change to FL treatment. 

It's fascinating to me to look a little deeper into a process that we don't think much about. And I love to see how excited people are about possibilities. It's a constant moving forward.

There's so much to be hopeful about.  

 

Cancer-Sniffing Dogs

 New from the Journal of Clinical Oncology: "Canine Olfaction Combined With Bayesian Modeling for Multicancer Detection From Breath Samples: A Phase II Study in India."

Of all the ways to detect cancer, the best has to be dogs who can somehow smell it.

(I know, I know -- the "best" is the cancer detection test that works the best at detecting cancer. But a colonoscopy doesn't love you unconditionally. That would make a great slogan on my Lympho Bob t-shirts, if I actually had any for sale.)

I'm fascinated by cancer-sniffing dogs. This study took place in India. The idea is that training dogs to sniff cancer might be especially helpful in what the authors call "low and medium income countries."  Cancer detection can be very expensive. Dogs will work for very little -- a couple of biscuits and a pat on the head.

Seriously, though -- as the authors point out, dogs have been trained to sniff cancer for 30 years. The first known cancer-sniffing dog was standard schnauzer named George, who was able to detect skin cancer. Studies that looked at cancer-sniffing dogs have mostly been small, and have taken place in higher-income countries. 

For this phase 2 clinical trial, 3275 patients were enrolled. 1773 were used in training the dogs, and 1502 in the actual testing. For the tests, patients breathed into cotton surgical masks, which were then stored at -20 degrees Celsius. 283 of the patients actually had cancer -- one of seven types (head and neck, breast, lung, gynecologic, upper and lower GI, and genitourinary cancers -- there were no blood cancers among them). Each mask was sniffed by three different dogs, and the collective results were combined.  The dogs correctly detected about 90% of the samples with cancer, and about 91% of those without cancer. They were just as accurate with stage I and II cancers as with later stage cancers -- important for those cancers where early detection can increase survival.

You might not have access to the JCO article, so you can read more about it here. The company that did the testing is called Dognosis. They are working on a system that will use AI to help pick up the signals that the dog is giving. (If you've ever trained a dog to do any kind of scent work, you know it can be hard to pick up their signals on your own.)

And if you're wondering what breeds of dogs were involved, they were four Beagles, one Labrador, one Labrador-Indie mix, and one Dutch Shepherd-Belgian Malinois mix. There was less than 2% variation between the dogs, meaning it really didn't matter which dog was doing the sniffing. They all did equally well in detecting the cancers. 

The reason I find all of this so fascinating is because I have owned two standard schnauzers -- like George, the first cancer sniffing dog. Our first, Strudel, was about a year old when I got my cancer diagnosis. If she noticed anything, she didn't let me know. Our current dog is Katara, who is 5. She didn't say anything about either of my skin cancers. Maybe I just haven't been listening very well.

 

We've actually done some scent work training with Katara, just for fun. And we've learned a lot about how sensitive dogs' noses are -- about 10,000 times more sensitive than a human's nose. Out trainer explained it to us this way: when we humans smell a chocolate cake, we smell a chocolate cake. But a dog can smell the flour, the eggs, the sugar, the cocoa, etc.  Their noses are really amazing instruments.

So if you have a dog, give them an extra hug today on behalf of all the work that other dogs are doing for us.

 

 

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.