ASCO: Barriers to Treatment in R/R FL

I'm continuing with my look at ASCO abstracts. In my last post, I mentioned that that you can sort the abstract search results by "Top Rated," so I looked at the "lowest rated" abstract then. I'm going about halfway down the list this time. I could look at the top of the list, but I'm guessing those will be discussed after the meeting is over, since they are likely to be about research that someone wants to brag about.

Is it just a coincidence that "top rated" abstracts tend to look at clinical trial results and other research on things like CAR-T and bispecifics, while the lower-rated abstracts tend to be about things like survivorship? Probably just a coincidence.

This abstract is called "Bridging gaps in relapsed/refractory follicular lymphoma care: Perceived barriers to treatment and clinical trial access." It looks at the special circumstances of patients who have Relapsed or Refractory disease -- that is, their last treatment stopped working after a while, or never worked at all.

It reports the results of a focus group of 25 people. A few words about what that means. If someone wanted to get the opinions abut Follicular Lymphoma from a group of people, they could do a survey (like this one from last year). The survey was answered by 337 patients from 25 countries. It's very valuable information -- all of them answered the same questions, which makes it easy to compare answers. You get a wide range of opinions.

A focus group involves a lot fewer people. Instead of filling in an online survey, a focus group is usually in person (or maybe by Zoom). The format allows the person leading the group to ask follow-up questions. And since the participants are listening to one another's answers, it often results in conversation. Both types of gathering information -- surveys and focus groups -- are valuable. But they do different things. Surveys result in breadth, focus groups result in depth.

So this group of 25 people provides some good information. They were actually divided into two focus groups included patients with Relapsed or Refractory Follicular Lymphoma, caregivers, and patient advocacy representatives. The other was made up of " multidisciplinary healthcare professionals (HCP) involved in R/R FL care in the U.S." Six HCPs and twp patients also had interviews to go into further depth about the subjects that came up in the larger groups.

Not surprisingly, there was some overlap in the outcomes from the two groups. Also not surprisingly, there were some places where they didn't agree.

The Health Care Professionals thought a few things were very important for R/R FL patients. The first was Individualized Treatment Sequencing. FL is a heterogeneous disease -- it acts a little differently for each of us, so each of us needs an individual plan for treatment. They also valued assessment for transformation, making sure patients were following closely for any signs of transformation to a more aggressive lymphoma. They also valued newer treatments when they seemed appropriate, and the need for clinical trials. They also emphasized SDM -- Shared Decision Making, where patients have some input into which treatments they would receive. 

Patients also valued many of those things. However, patients said there were varying degrees of Shard Decision Making -- some felt empowered to make decisions, while others were given limited options. The patients also said that emotional support was inconsistent, and often they only received it when the patient or the caregiver made an effort to find it. (I assume this emotional support is something formal, like access to a therapist.) Patients also valued clinical trials, but noted "limited information for refractory disease" and unequal access to trials, though some (again) were able to gain access when they made the effort to get it. Patients also pointed to how they could have a better experience with Shared Decisions Making -- by trusting relationships with HCPs, getting better access to accurate information, and engaging with patient organizations for peer support.

The researchers conclude that while Shared Decision Making is a priority for both groups, there is a need for more intentional strategies to make it happen -- better communication, patient education, and structural support.

The good thing from research like this is that is encourages more of the work to be done by the HCPs, the hospitals and cancer centers, and other people and organizations from that end of the spectrum. In other words, the people who have knowledge need to find better ways to share that knowledge with patients. They think they are, and most are doing their best. But "intentional strategies" are important -- creating formal processes to make it happen all the time, not just when a patient or caregiver asks for it. 

That said, "intentional strategies" take time to create. And oncology tends to be habit forming -- even if a new way of supporting patients is available, sometimes doctors need a push to make it part of their routine. 

So it's still going to be important for us as patients to educate ourselves, be proactive, and make sure we are getting what we need.  

The ASCO conference starts in a coupe of days, so I expect some nice press releases and video analyses to start showing up soon. I'll be sure to share the good stuff with you when I find it.

 

ASCO Abstracts Are Here! (plus, Survivorship!)

Huzzah!

ASCO has published their abstracts! It's like Cancer Nerd Christmas!

If you have no idea what I'm talking about, ASCO is the American Society of Clinical Oncology. It's the largest professional group for oncologists in the United States. Every year in late May or early June, they have their annual meeting. It's the largest gathering of oncologists in the U.S., and it's where many researchers present their work -- results from phase 1, 2, and 3 clinical trials, theoretical work, research on cancer biology that might lead to clinical trials. This year, the meeting is taking place May 29 to June 2. 

About a week or two before the meeting, ASCO releases the abstracts -- the summaries for all of the presentations.  The people who go to the meetings use the abstracts to decide which presentations they want to hear and see, so they can more details. I have never been to an ASCO meeting -- it always comes at the worst time of year for my job. (The other major meeting for blood cancer research, ASH, comes in December, at the second worst time of year for my job. When I retire, I'm going to go to all of these cool meetings.)

The ASCO Abstracts were released yesterday, so I can finally see all of the cool new research that is being presented. Like I said -- it's Cancer Nerd Christmas.

I did a quick search on the Abstracts page for Follicular Lymphoma, and 29 presentations came up. That's a little less than in the past, and a few more may show up, but there are definitely a few that are worth paying attention to.

Over the next few weeks, I'll write about some of the abstracts tat look particularly interesting. And while the conference is happening, and in the days after it is finished, there will be lots of press releases and video commentary about the presentations that are most significant, so I'll write about those, too. It's usually about a month or so of ASCO news from here. It's all very exciting.

So I might as well start with an abstract right now: "e24130: Living after lymphoma: A retrospective study of survivorship outcomes from a tertiary cancer centre in rural India."

On the abstracts page, you can sort the results in a few different ways, but the default for me was "Top Rated." I don't know who is rating the abstracts or how they are rated, but I thought it would be interesting to go down the very bottom and see which one was apparently rated last (whatever that means).

And so we have "Living after lymphoma: A retrospective study of survivorship outcomes from a tertiary cancer centre in rural India."

If you've been reading for a while, you've picked up that the idea of "survivorship" is becoming much more important to me lately. Many cancer patients complain that they get excellent care when they are diagnosed and in treatment, but after all of that is over, when they are "finished," nobody seems to care. So there are many cancer centers that have Survivorship Clinics that help cancer survivors deal with the long-term physical, emotional, and mental challenges that come when cancer is "finished."

So this particular title, with "survivorship" as part of it, certainly caught my eye.

It looks at 100 Lymphoma patients in a cancer center in rural India who were diagnosed between 2012 and 2022. They were diagnosed with several different Lymphomas, including Diffuse Large B-cell Lymphoma (45%), Follicular Lymphoma (17%), Hodgkin Lymphoma (20%), and others (18%). Almost all were treated with some kind of chemotherapy (97%). Other treatments included radiotherapy (20%) and autologous Stem Cell Transplant (9%). The researchers collected information about the patients, including "demographics, disease characteristics, treatment exposures, metabolic parameters, endocrine function, bone health, cardiovascular events, secondary malignancies, and psychosocial outcomes."

They found a wide range of long-term issues that the patients had to deal with: Metabolic complications like obesity (40.4%), hypertension (31%), high cholesterol or triglycerides (56%), diabetes (31.1%),  hypothyroidism (8.4%) and vitamin D insufficiency or deficiency (76.5%).

Other health issues included osteopenia (37%) and osteoporosis (23%). In addition, "Two patients developed new-onset left ventricular dysfunction, three experienced cerebrovascular events, and two developed premature cataracts before the age of 50. Two patients developed tuberculosis post-treatment. Second primary malignancies occurred in two patients." Finally, "Psychosocial impact was notable, with five patients remaining unmarried and one experiencing marital disruption attributed to fear of recurrence and social stigma."

The researchers conclude that greater survivorship care is needed for patients in rural India.

I'd say that is probably true no matter where we live.

I look at that list of issues, and almost half of them apply to me as well. So I'm not sure it's a problem confined to rural India. One difference might be that I may have better access to treatment of those long-term health issues. My heart-related issues are under control because I take a handful of pills every day. 

But I have to say, I see very little research on the long-term side effects of cancer treatment. Or maybe I should label them "very long-term side effects." After that 5 year mark, there isn't much attention being paid.

I guess the attitude is "Hey, you're alive after 5 years. Of course you'll have some health issues from treatment. And there is only so much time and money available for research, so we need to put our focus elsewhere." That's true, but if nothing else, more attention paid to very long-term side effects might mean more attention is paid to Survivorship and to the resources that are already available and under-used. (Read about research on survivorship services from a couple of years ago.)

I think I'd feel better if this presenttaion wasn't at the bottom of the "Top Rated" list." 

Wasn't that a good one to start with? Lympho Bob is feeling a little salty, as the kids say. 

I'll be sure to look at the top of the "Top Rated" list soon. I'm sure it will be much more exciting, and I'll have more positive things to say.

It's still a great Cancer Nerd Christmas, and I'm ready to open some more presents. 

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. 

 

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. 

 

FLF Webinar on Health Data

The Follicular Lymphoma Foundation's next webinar will be "Your Health Data: How It Powers Research." It will happen on Friday, March 27, at 7am PT / 10am ET / 3pm UK / 11pm UTC. 

As with all of the FLF webinars, this one will feature a Lymphoma expert and a patient or caregiver. The expert is Dr. Peter Martin from New York Universioty Langone's Perlmutter Cancer Center in New York City. He is active with a group that promotes clinical trials for Lymphoma. The caregiver is Cris Carrigan, whose wife was diagnosed with breast cancer. He also has a professional background in cancer data. He is involved with a charity in the UK called  Use MY Data, made up patients, relatives, and caregivers who encourage cancer patients to allow their data to be used for research.

Use MY Data is an interesting organization. They don't hold any patient data. They encourage patients to allow their data to be used in clinical trials and other research. I don't know of any similar organization in the US.

The fact that such an organization even exists says something important.

I completely understand patients' reluctance to share their data. We live in a world where our data of all kinds -- financial, personal, medical -- is in danger of being stolen or shared. And we want to keep it close. Like I said, I understand. I've been given opportunities to work on certain projects that seemed interesting, but then I was told my medical records would need to be accessed. I backed away. I'm happy to share information if I have a good sense that it's going to help others (that's the whole point of this blog, after all).  But I'm crazy about the idea of giving unrestricted access to my electronic health records, especially if I'm not getting clear answers about how it will be used.

But that doesn't mean I would never share it under the right circumstances. If there was data that I thought would be helpful in finding a cure or helping other patients, I'd absolutely share it.

Think about it. If there were a large database of patient information that could be accessed by researchers that could help them better understand Follicular Lymphoma, wouldn't that be great?

That's where a group like Use MY Data comes in. Their mission is to encourage data use, but also to promote responsible and accountable use. 

Still skeptical? Understandable.

Then attend the webinar and see what they have to say.  And if you can't attend live, remember that recordings of all if their webinars are available later on.

I think it's going to be a very interesting session. 

No More Tazemetostat

The news came out this week that the makers of Tazemetostat will no longer offer this treatment to patients, including patients with Follicular Lymphoma. There are too many concerns about patients developing new, different cancers.

They made an announcement about a month ago that they were stopping a clinical trial that was testing it, and now they have decided to just pull it from the market completely.  

Tazemetostat is an EZH2 inhibitor. It works by inhibiting or stopping an enzyme called EZH2, or Enhancer of Zeste Homolog 2." This enzyme is controlled by the EZH2 gene. EZH2 keeps tumors growing, so when it's not doing its job, it needs to be inhibited -- stopped by Tazemetostat. About 20% of FL patients have an issue with their EZH2, though it can also be effective on patients that don't have that particular mutation.  

Tazemetostat was approved by the FDA in 2020 based on its ability to help that 20% of FL patients -- it was the first treatment that successfully helped that group of patients. The FDA approval was accelerated, meaning it was approved based on a small phase 2 clinical trial, rather than the usual, larger phase 3 trial. The accelerated approval, as always, is based on continuing research. A larger phase 3 confirmatory trial must be run to make sure the treatment is as effective and as safe as the smaller trial suggested.

Accelerated approval can be great. But sometimes the phase 3 trial that comes after approval shows some problems. And in this case, that problem was that the treatment may be causing secondary cancers. I haven't seen anything about how many patients developed the new cancers, or what kind of cancers. 

If you're wondering what happens to the patients in a cancelled trial: in this case, they will continue to receive treatment. The trial (called SYMPHONY-1) involved 2 groups. One received R-Squared (Rituxan and Revlimid) + Tazemetostat, and the other received just R-Squared. So patients who were enrolled in the trial will all continue to receive R-Squared. They won't be left without treatment. 

I have mixed feelings about accelerated approvals. They make new treatments available to patients who might need them. But they also risky in that they haven't gone through the full process that other treatments have gone through. On the other hand, even if there had been a phase 3 trial, the patients who volunteered for it would still be dealing with the same risks. It's all very complicated.  

The unfortunate part for all of us is that we have one less treatment available to us. And for those with the EZH2 mutation, that's even more unfortunate.  

But we can stay hopeful. There are lots of treatments available to us, and many more potential treatments on the way. 

 

 

More on the 15 Year CHOP Follow-Up

As I wrote in my last post, I have been looking for commentary from Lymphoma experts on the 15 year follow-up of FL patients who received CHOP. The researchers are suggesting that 42% of patients in the study were cured. I've been looking at Twitter/X, where there is usually a decent amount of commentary about Lymphoma, as well as in all of the google alerts I usually get.

There really hasn't been a whole lot of commentary. Most of what I have seen has been repeating the results of the study, rather than giving an opinion on it. One of the very few comments I have seen came from Dr. Mitchell Smith, the Chief Medical Officer for the Follicular Lymphoma Foundation. In a Facebook post from the FLF, he was quoted as saying:

"These findings are encouraging and confirm that some patients have very long-term remission after treatment. The challenge remains that we cannot yet predict which patients will be in this group. Follicular lymphoma is a complex cancer, and many patients live with the disease for many years with different treatment approaches. Studies like this help us better understand long-term outcomes while reinforcing the importance of continued research."​

 

The response is measured. It is positive and recognizes the importance of the research, but also makes it clear that there is more work to be done. The more I think about the study, the more this reaction makes sense. We've always known that some treatments give some patients very long remissions, not just CHOP. As I mentioned in the comments last week, I know a few people who have had RIT and are still in remission over 20 years later. That can be true for Stem Cell Transplants as well. And while I have never technically been in remission (I've never had a completely clear scan), I've been living with the disease for 16 years without needing another treatment, after I had six rounds of Rituxan. 

 

What's different here is that this research looks closely at a group of people who received the same treatment. A story about one person in remission is an anecdote, not a research study. This research is large enough, long enough, and rigorous enough, to have its authors dare to use the word "cure." But there is still work to be done, as Dr. Smith says.

 

Overall, I'd say there is reason to celebrate, but not to rest. It reminds me a little of the scene from the movie Elf (one of my family's favorites). Santa returns from delivering toys and says to the elves "We had another successful year!" The elves cheer, and Santa says, "And now it's time to start getting ready for next year!" The elves immediately go back to work. Worth celebrating, but there's work to be done.

 

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Speaking of the Follicular Lymphoma Foundation, they have started a new series on their blog called "Science Simplified." In a series of posts, they will discuss some current research in FL in ways that make it easy to understand. Their latest is called "Who Needs Treatment and When?" It discusses some of the research at this year's ASH conference, focusing on GELF criteria. GELF is a French group, Group d'Etude des Lymphomes Folliculaires. In 1997, they proposed a set of criteria for when FL needs to be treated, and when a patient can watch and wait. The FLF blog post discusses an ASH presentation that examines the GELF criteria and how doctors make decisions about when to begin treatment. 

 

You Cancer Nerds will enjoy reading about research. And the rest of you (especially those of you who are watching and waiting) might enjoy reading about the practical implications of the research. 

 

More to come soon. Thanks for reading. 

R-CHOP 15 Year Follow-Up: A Cure for FL?

The big news in the world of Follicular Lymphoma this week is an article in JAMA Oncology describing results of a 15 year follow-up of FL patients who received R-CHOP (or CHOP + Radioimmunotherapy). The study suggests that 42% of the patients in the cohort have been cured of their FL. It's a big deal because it's really the first time anyone had seriously suggested that FL might be curable.

There's a lot going on in this study. It's worth looking into a little further.

The article is called "Treatment of Follicular Lymphoma With CHOP and Anti-CD20 Therapy: 15-Year Follow-Up of the SWOG S0016 Trial." The goal of this analysis was to see how many of the patients in the trial were cured after 15 years. They determined which patients were cured by a statistical method called "cure modeling," which provides an estimate of how many patients were cured.

I think that's important to note here. Part of the problem with determining whether someone is cured has been the nature of FL. With many other cancers (as I'm sure you are aware), if a patient is disease free after 5 years, they are often considered cured. That's harder with FL, since some patients will have the disease return after 6 years, or 10 years, or 15 years. So it's risky to say someone has been "cured" of their FL. 

And it's why many FL experts use the term "functional cure" instead. Someone can be diagnosed at 65, get a Complete Response, and never need treatment again, and die of something unrelated at 85 years old. Were they "cured"? It's hard to say. But they lived a life as if they were cured -- it was a "functional cure."

So this study defined "cure" using statistical methods because it's really difficult to say whether or not someone was cured the way they could for patient with something like colon cancer.

I won't pretend to understand the statistical analysis of the cure modeling, but I will say that since the article was peer-reviewed, it would have been approved by other experts in statistics before it was published, so I don't have any doubts about the analysis.

The SWOG study itself involved 531 patients. They received either R-CHOP or CHOP-RIT between May 2001 and October 2008. I don't write about CHOP much these days, so a reminder: CHOP is a traditional chemotherapy made up of four components (Cyclophosphamide, Hydroxydaunorubicin/doxorubicin, Oncovin, and Prednisone). It's been around for a while, and it's still a very popular treatment. R-CHOP is CHOP combined with Rituxan (rituximab/mabthera). When R was added to CHOP about 30 years ago, it increased its effectiveness. It's pretty standard now to include R with CHOP. RIT, RadioImmunoTherapy, is a treatment like Zevalin. It's essentially something like Rituxan, which can find the CD20 protein on a Lymphoma cell, but with a tiny bit of radiation attached to it, so the radiation can be delivered directly to the cancer cell. 

So of the 531 patients in the study, 267 received R-CHOP and 264 received CHOP-RIT. The 15 year Overall Survival rate was 70%, about the same for each of the two groups, though the RIT group had a better 15 year Progression Free Survival (the cancer didn't come back for 15 years for 47% of the CHOP-RIT patients, versus 34% of the R-CHOP patients). 

The cure modeling estimated that 42% of the patients in the study had been cured. The highest cure rates were in patients with low FLIPI scores and normal β2 microglobulin levels, essentially the patients with the lowest risk. (You can read more about FLIPI levels here, but keep in mind that it doesn't say anything about you as an individual, even though it seems like it does.) This isn't a surprise, really -- we expect less aggressive version of FL to be less problematic and more successful with treatment.

One important finding of the study was that the rate of relapse declined over time. For the first 5 years after treatment, 6.8% of patients in the study relapsed. But between years 15 and 20, just 0.6% of patients relapsed. So the longer the patients went in the study without relapsing, the less likely it was that their disease would come back. 

That's really important. Think back to the idea of "functional cure." It's hard to say someone is "cured" because the disease might come back after 10 or 15 years. But this study shows that it's much less likely to happen, so someone can be more confident after 15 years that the "functional cure" is an actual cure.

Te conclusion to all of this from the researchers is that maybe FL isn't incurable after all. The call this a "paradigm shift" -- a complete change in the way we think and thus the way we act. It could mean that doctors have very different conversations with patients, and that maybe R-CHOP is presented as a possibility for someone who might want a cure. It also has implications for future research.

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As I said, there's a lot happening here. This article was published about 4 days ago, and I've been waiting to hear what other FL experts have to say. So far, I haven't seen or heard much, but I think everyone is trying to take some time and digest it all. Paradigm shifts don't happen in 4 days -- they take years for everyone to break out of the way they have been thinking for so long (at least according to Thomas Kuhn).   

And I absolutely understand that. We (meaning much of the Lymphoma community) get so locked in to the idea that "newer is better" -- that every new CAR-T or bispecific or inhibitor must be an improvement over chemotherapy -- that's it hard to see a study like this and not be skeptical. It's certainly my own reaction to it, and I immediately start with a long list of "Yes, but" statements. "Yes, but it's just a statistical estimate, not an actual look at the patients." Or "Yes, but 42% is hardly a cure for all of us." Or, "Yes, but it's still a fairly small number of patients in the study, compared to the thousands that are diagnosed every year."

Particularly for me as a patient who was diagnosed 18 years ago, and who has been told this is incurable for all of that time, it's pretty tough to suddenly think otherwise, and even tougher to think the cure might be from chemotherapy.

That's why I'm especially impressed with the statement from Dr. Jonathan Friedberg from the University of Rochester Wilmot Cancer Institute. He was one of the authors of the study, and he's the one who is talking about paradigm shift (see the story that came out of the Fred Hutch cancer center where he is quoted). He's a Lymphoma Rock Star, doing cutting edge research on FL, and he's willing to look at the data and say "Maybe it's chemotherapy after all." 

The few comments from Lymphoma specialists that I have seen have been positive. It's clear that no one expects R-CHOP to suddenly replace bispecifics and CAR-T. But it could mean that conversations with patients are different. For some patients with low risk disease, and who are otherwise healthy and can tolerate the side effects, maybe R-CHOP is an option. CHOP contains an anthracycline, a type of drug that can be very effective but can also cause long-term heart issues. That kind of factor will need to be taken into consideration. 

I saw one commentor who said this study will have an effect on future research in a couple of ways. First, long-term studies of FL treatments will be measured against this. It's really interesting that this come out just after a 15 year follow-up of R-Squared. It's a much smaller study -- only 79 patients. But could the same cure analysis be applied to it? Could it be applied to a larger study of 500+ patients? If it was, could we make a direct comparison between the two treatments? It will be hard to look at any long-term study of an FL treatment now and think "Yeah, but....does it have a better cure rate than 42%?"

Another way this might change research is that there might be a greater emphasis on second-line treatments. That emphasis already exists, in some ways -- most new treatments get approved for relapsed/refractory disease first, and then as first-line treatments. But this cut back on the number of treatments that do that second step and get approval as a first-line treatment. In other words, we could possible have something closer to an agreement on how newly diagnosed patients are treated, and that treatment could be traditional chemotherapy. 

That's not to suggest that everyone will be getting chemo from now on. There are and will be lots of options out there, and more to come, for a long time. But I expect those conversations to happen.

I'm going to keep an eye open for more commentary about this. I expect some of the oncology websites to have videos of experts discussing this. I'm hoping for more debate-style videos, with multiple experts arguing for and against using R-CHOP. They would be more enlightening to me.

But I think the main take away for all of us should be the same thing. For at least some FL patients, a cure may be possible. For the first time, people seem willing to say so. 

Exercise Recommendations for Cancer Survivors

I've seen two articles in the last couple of weeks that are focused on the importance of exercise for cancer survivors. As you probably know from reading, I have become more and more focused on the role of survivorship lately -- the things we do after diagnosis and treatment that can improve our Quality of Life. 

The articles about the importance of exercise has especially caught my eye for a few reasons. 

First of all, I've been in Physical Therapy for a knee problem for a few months. I've been strengthening my leg muscles to help stabilize my knee, and I'm remembering how much I used to enjoy those kinds of exercises. I don't go to the gym much these days, but the PT work is a lot like a gym workout.

Second, for the last few weeks, I've been attending a yoga class. I tried a Tai Chi class, which I was excited about, but I had to stop it because of my (unrelated) knee issue.  I'm enjoying the yoga class, which is called "Yoga for Healthy Aging." The movements are gentle, but it's still a workout, and the focus is on things like flexibility and balance that we all need as we age. I'm the youngest person in the class; one man introduced himself by saying "I've been doing yoga since I was 83 years old." How's that for inspiring?

Third, I spent two nights watching the Olympics. I love cheering for the "old" athletes -- anyone over 30. More inspiration to get up and move.

Because I like to move my body, and I find that I feel better when I do.

The first of the two articles I saw was the JAMA Network from last week, called "Leisure-Time Physical Activity and Cancer Mortality Among Cancer Survivors." This article reported on research that looked at six different large studies from the past. The studies each looked at survivors of bladder, endometrial, kidney, lung, oral cavity, ovarian, and rectal cancer. The participants in the studies completed surveys and had their leisure-time physical activity tracked 1976 through 1997. There were 17,141 cancer survivors in the combined studies.

The researchers found that even low amounts of moderate to vigorous physical activity resulted in lower risk of death from cancer for patients who had been diagnosed with bladder, endometrial, and lung cancer. Doubling the recommended amount of exercise was associated with lower risk of death from cancer for patients diagnosed with oral and rectal cancer. For some patients in the study, their risk of death from cancer improved when they exercised even if they were inactive before they diagnosed. 

Now, there are all kinds of reasons why this doesn't really prove anything for us. There were no blood cancer survivors at all in this study, and it took place many years ago. But it's one of many that show that movement can be beneficial for cancer survivors; the first words of the Introduction the study are "The role of physical activity (PA) in mitigating cancer risk is well recognized." 

At around the same time, I saw a article from last month from Cancer: Interdisciplinary International Journal of the American Cancer Society. It's called "Exercise recommendations for older adults living with and beyond cancer: A consensus statement by the Advancing Capacity to Integrate Exercise Into the Care of Older Cancer Survivors expert panel."

The idea behind this was that there are lots of recommendations for older folks to exercise, but none that take into account the unique needs of cancer survivors over 65. This article presents some guidelines for how that group of folks should consider exercising.

To be clear, it doesn't recommend specific exercises, which is kind of the point. It assumes a few things -- first, that some cancer survivors over 65 do not move as much as they should. Second, that they have specific needs as cancer survivors. And third, that everyone's situation will be a little different. That's important. My exercise needs aren't the same as yours.

So the guidelines are kind of general. They start with the idea that someone who is a recent survivor should get a full medical evaluation before they begin exercising, and should the be evaluated by someone who understands how to make sure someone can handle the exercise they might want to do. They recommend tests for things like mobility and balance -- things that can be affected by the side effects of the disease or by treatments. They also recommend that an expert help design an exercise program, make sure that it is being followed safely and correctly, and that behavioral support is also offered (because it's pretty easy to get discouraged when you start exercising and you can't do everything you wish you could).

The principle guiding all of this is that barriers and risks should be kept as low as possible. The program should be manageable and enjoyable, not creating more mental or physical problems than the person started with.This is ultimately about Quality of Life -- being able to do the things that you want to do. That can be a struggle for some of us, especially as we get older, and especially as we deal with the effects of cancer. 

So, to me, the personal message from all of this is to keep doing what I'm doing. My wife and I still walk about 2 miles every morning with our dog. I'm in physical therapy for my knee, not ignoring problems until they get worse. I wish I had enjoyed Tai Chi as much as I had hoped I would, but that's OK -- I'm trying yoga instead. And if this doesn't work out, I'll try to find something else. But I'll keep trying and keep looking.

As we get older, my wife and I seem to collect doctors. We have a new health condition or  new prescription every six months or so. But we also have goals, like continuing to travel. And so taking care of ourselves physically becomes very important to us. Quality of Life -- doing the things that we want to do. 

So wherever you are physically, I hope you'll take some inspiration from the Olympics and try to start moving more. (And take advice from your doctor first.) I had lots of inspiring Olympic role models from the U.S. to choose from, but I have to say, the most impressive to me was Johannes Høsflot Klæbo, the cross country skier from Norway. He won every cross country event, from a sprint of 1,585 meters (about one mile) to a 50 kilometer race (about 32 miles). At one point, he was running uphill on skis at a pace of a 6 minute mile. Just amazing to be that great in so many different ways.

Take your inspiration where you can. But keep moving forward.