Bispecifics vs CAR-T: The Difference in Cost

Good news: It's November, so the ASH abstracts are now available online.

For those who don't know or who need a reminder, ASH is the American Society for Hematology, and every year in early December, they hod their annual conference. It's the largest gathering of blood cancer specialists in the U.S., so there is usually some good research on Follicular Lymphoma that is presented. 

I haven't had a chance to look deeply into the abstracts yet, but I will soon. And as I usually do, I'll try to write about some the research that interests me and that I think will interest you, too. 

I've been so busy lately that I actually forgot that ASH was coming up soon. I got an email from Wendy, a very well-informed reader who reminded me that it was coming up.

And that reminded me to look at some of the links I have been collecting for the last month or so. I'm assuming there will be more research on bispecifics and CAR-T, the two treatments that, in my opinion, are the ones that get blood cancer specialists the most excited.  

One of those links that I saw very recently was about a presentation at the Academy of Managed Care Pharmacy (AMCP) Nexus, a gathering of pharmacists in managed care networks. Managed care refers to health care systems that aim to manage costs while not sacrificing quality. That's the aim, anyway. The important point is, the folks at this conference are as interested in how much a treatment costs as they are in how safe or effective it is.

The presentation that caught my eye is called "Total Cost of Care and Adverse Effects Assessment of Bispecific T-cell Engagers and Chimeric Antigen Receptor T-cell Therapies for Relapsed Refractory Follicular Lymphoma." The point of the research was the heart of what I said about managed care -- it wanted to look at how bispecifics compared to CAR-T, in effectiveness and safety, but also cost.

 I probably could have predicted the outcome of this. CAR-T is an exciting development in treatment, but it's also very expensive. The cost, when it was first approved, was about $500,000, give or take $100,000. That's a lot of money. I was in a meeting recently with some other FL patients, and one mentioned that she had been told that CAR-T, without health insurance, could cost as much as $2 million. (I don't know if that's true, but it certainly made me take notice.) 

In the research from this conference, the researcher looked at TCOC -- Total Cost of Care. That would help the high cost of CAR-T make sense. CAR-T is a personalized treatment, in which T cells are removed from a patient, changed in a lab, and then put back into the patient. That personalization is going to add to the cost. In addition, because of some potentially dangerous side effects, CAR-T patients are typically admitted to the hospital for as long as two weeks -- another factor adding to the cost. 

For some health care systems, that might make the treatment worth the cost, if it is so effective that the patient will never need another treatment again.

Ultimately, the study found that bispecifics might be a better choice for managed care. That is, they can be as effective, and as safe, but cost less. 

The Total Cost of Care for the CAR-T patients in the study averaged $702,000, while the bispecific patients' average total cost was $372,000. The total cost of the drug itself (as opposed to including hospitalization and other costs) was $521,000 for CAR-T, and $183,000 for bispecifics. 

The researchers also found the cost included having to deal with side effects. 52% of the CAR-T patients had significant side effects, adding about $9000 to the cost of care, while 23% of bispecific patients had side effects that added about $500 to the cost. 

(If you're not in the U.S. and all of these costs confuse you, try using a currency calculator. I'll post one here for your convenience, but there are plenty online.) 

I really hate thinking about treatment in terms of cost. I'd much rather write about the happy news that a brand new treatment had a 90% Complete Response Rate with manageable side effects. And that's what I usually write about.

But I know it's not the reality. I know many of us get certain treatments because if someone else is paying else is paying for them, they want to spend as little as they can. And that's true whether it's a private insurance company like in the U.S. or a public system like in Canada or the U.K. And I also know that sometimes I write about exciting new treatments that aren't even available in some countries -- at any cost -- because the cost is so high that it's not worth even making them available.

So it's probably good to know some of this insider information on how much things cost and how decisions get made.

One of the frustrating things about FL treatment is that there are no easy answers, no one clear path for treatment. It would be great if we could say the first line treatment should be X, and then if a second treatment is needed, it should be Y, etc. We don't have that certainty. There are lots of treatment options available that can do a good job.

But maybe there's some comfort in that, too. Maybe if we think a certain treatment that excites our oncologist would be the right one for us, but which a payer refuses to pay for, then we know there are other options. They will be less expensive, and maybe less effective, and maybe with a few more side effects. But we have options, anyway.

That's not necessarily the happiest way to think about it. But it's certainly realistic. And cancer makes us all realists.

I hope it's a long time before you need to make any tough choices. Take care.

  

Restoration

 Hello all. I want to let you know about a new piece that I have written that was just published in Intima: A Journal of Narrative Medicine.

It's called "Restoration," and I have to say, even with as much as I write, I'm more proud of this piece of writing than I have been of anything I have written in a long time.

I won't spoil it for you, but I can tell you that the "restoration" in the title refers to two things. The first is furniture restoration. It's a hobby of mine -- finding old wooden furniture that someone is throwing away, and  fixing it up, either to keep or to donate to someone else who might need it. "Restoration" of furniture is about trying to bring the furniture back to what it once was, before age and use made it something different.

"Restoration" also refers to our attempts to restore ourselves. As cancer patients and survivors, sometimes we wish that things could go back to the way they were, before diagnosis, before treatment, before everything else that comes with cancer. But furniture can never really be "restored." You can never bring it back to the way it was when it was created, as much as it might look like it used to be. And it's the same for us -- we can never really be the person we once were. And that's OK. Sometimes "renovation" is good enough for an old chair or side table -- making it something new, not making it was it was. And maybe we're the same way ourselves.

As I said, I was really happy with the way it turned out, because it was an idea that I had been turning over in my head for a long time, trying to make sense of it. I was finally able to say what I wanted to say, in the way I wanted to say it. I hope some folks find it valuable. Writing is good that way.

So if you'd like to read it, you can find it here. Thanks for clicking.

More Follicular Lymphoma stuff coming very soon. 

Take care.  

Music Therapy for Cancer Anxiety

My most recent email from CURE Today had an article on a recent clinical trial that looked at the benefits of music therapy on anxiety in cancer survivors.

The trial results were actually presented at the ASCO conference in the spring. The presentation was called "Music therapy versus cognitive behavioral therapy for anxiety in cancer survivors: A telehealth-based randomized clinical trial." In the trial, 300 survivors of different types of cancer were split into two groups. All of them had reported anxiety for at least one month. (It probably was not hard to find cancer survivors with some anxiety.) The people in the first group were given Cognitive Behavioral Therapy. (You can read more about CBT here; in the trial, it was considered the standard of care -- the treatment that most people would get if they had anxiety.) The folks in this group met with the therapist once per week for seven weeks by Zoom or other telehealth system.

The other group had music therapy once a week for seven weeks. A separate description of the trial said this consisted of "custom treatments" created by a music therapist "that may involve listening to music, singing or writing a song."

The results showed that the music therapy was non-inferior to the CBT. In other words, the folks in each group experienced about the same reduction in anxiety. The goal of the trial was to show non-inferiority, not superiority. In other words, the researchers wanted to show that both options were useful, rather than showing one was better than the other. CBT works, but some survivors can't do, or don't like it, so having another options -- especially one that is convenient because it can be delivered virtually -- is important. 

One of the big conclusions of the study is that Music Therapy has a long-term benefit. Listening to music, or singing, or writing a song can have a short-term effect that we've probably all experienced.  Your favorite song comes on (Maybe Lizzo's "Good As Hell," to give a completely random example), and it makes you feel good to hear it or sing it or dance to it. But doing it consistently, or time, can have positive effects on anxiety as well.

 I write about music here occasionally. I'm one of those people who remember song lyrics. I'm getting to an age where I forget why I walked into a room and have to turn back around and try to trace my steps and thoughts to remember. But I can sing all the words to the theme song from the TV show "Hello Larry" from when I was 12. So I have millions of words stored somewhere in my brain that show up at times without my asking. Some songs kind of haunt me. They have innocent lyrics that make me think about difficult things. And some that are just fun and make me happy. And some that are really sad, and I like them too, because they can make me sad for just a few minutes and kind of get it out of my system. (Aristotle figured all of that out about 2300 years ago.)

All of this got me thinking about conversations I've had with other cancer patients and survivors who have told me about their favorite Cancer Songs, the ones that they listen to to when they need that short-term boost. Many of them of meant to be inspirational. Some seem to have no connection to the idea of trying to pick yourself up. And a bunch of them, I confess, are songs that I don't like at all, and if I had to hear them every morning to inspire me to face the day, I'd probably stay in bed. What inspired one of us doesn't inspire all of us -- and doesn't need to.

I'm going to share the Cancer Song that I enjoy most.  I've shared it here before. It's called "Swim" by a band callad Jack's Mannequin. Their lead singer and songwriter, Andrew McMahon, is a survivor of Acute Lymphoblastic Leukemia. The song is about trying to stay afloat when things are difficult. You can read the lyrics here -- it's pretty easy to believe it was written by someone who had been given a cancer diagnosis.

So here's my question for you -- what's your Cancer Song? What music inspires you when you're having one of those tough days? Share in the comments. I'm always looking for new inspiration.

And this research is a good reminder that you don't have to struggle alone when things seem overwhelming. The trial is about survivors, but remember that anyone who has been diagnosed, and is still alive, is a survivor.  If you're having a bad day, and putting on some music makes you feel better, that's fantastic. But if things seem overwhelming, and Taylor Swift isn't helping, it's OK to find help. The study is about people working with trained therapists, not about people trying to do it alone. 

Take care of yourself.

 

FDA Fast Track Designation for EO2463

Last week, the FDA grated Fast Track designation for a new immunotherapy treatment called EO2463. (It will probably get a cooler name soon.)

Some reminders before we go any further: Fast Track designation means that a proposed treatment has the potential to do something new, and so it gets extra help from the FDA to help it through the approval process. Its a way of trying to get treatment to a group that has great need for treatment. In this case, that group is Follicular Lymphoma patients. (The news article about this is not clear about the specific population of FL patients, though the National Cancer Institute page for the clinical trial specifies relapsed/refractory patients with FL and some other indolent blood cancers.)

 Immunotherapy is a group of treatments (like chemotherapy is a group of treatments) that uses the body's immune system to work against the cancer. Our immune systems are usually good at fighting off invaders, like bacteria or viruses). But cancer cells aren't invaders -- they are our own cells, but they refuse to die like they are supposed to. So immunotherapy treatments usually work by either changing our immune cells to find and fight the cancer c ells, or changing the cancer cells so they can be recognized by our immune system as invaders.

EO2463 is a very interesting treatment that takes a unique approach to identifying tumor cells. It's a little complicated, so I've tried to do a bunch of reading and watching to help me understand it. (This video helped.)

The company that makes the treatment focuses on bacteria in our guts. Gut bacteria is kind of big news these days, as researchers are looking into all kinds of ways that our gut biome affects our health. (Though not all of those claims have solid evidence.)

The role of gut bacteria in this treatment is different. The company uses Artificial Intelligence to identify over 20 million different proteins that exist in the gut. Their AI program can help identify proteins that are very similar to those that exist in the body, especially proteins that exist on certain cancer cells.

That distinction between the gut bacteria proteins and the human proteins is important. The bacteria in our gut play important roles, but they aren't meant to leave the gut. If they do leave it, our immune system takes over. Immune cells are meant to recognize and fight off invaders (like bacteria or viruses). When they encounter one, they eliminate it and then remember it, so if they encounter it again, they can eliminate it very quickly. Gut bacteria are included on that list of invaders. As long as they stay in the gut, they are welcome to hang around, and the immune system leaves them alone.

So we have two things happening here. First, you have gut bacteria that are considered invaders if they leave the gut. Second, you have proteins from the bacteria that are very similar to proteins on cancer cells, like the CD20 protein that is on the surface of Follicular Lymphoma B cells. 

When you put those two things together, you can develop a cancer treatment. Create a treatment that targets CD20 (and some other proteins) but create it in such a way that it tells immune cells that the cancer cell is really a bacteria that escaped from the gut and needs to be eliminated. Because the treatment is engaging an immune cell called a Memory T Cell, which remembers invaders, the thinking is that the treatment will be long-lasting.

[A note to you language nerds: I know that "bacteria" is the plural form of "bacterium," but I'm calling a single one a "bacteria" anyway because I think it sounds better. Shakespeare made up words, too, and it's my blog, so I do what I want.] 

The Fast Track designation was earned by the results of the SIDNEY clinical trial. This is a phase 2 trial involving 60 patients split into 4 cohorts. As I said above, there are several different blood cancers being targeted in the trial. Patients are given EO2463 on its own and in combination with R-Squared or one of its components, Rituxan or Lenalidomide/Revlimid. 

The early results are promising. The first 13 patients have an Overall Response rate of 46%, with no severe side effects. The makers of the treatment see this as a possible alternative to watching and waiting (though it's not clear if they are targeting untreated patients.)

I have to say, I'm kind of fascinated by the approach, using AI to identify possible targets based on gut bacteria. But there are also lots of questions to be answered -- as is always the case with a phase 2 study. My guess is that there will be more information at the ASH conference, which is happening in less than 2 months. 

But Fast Track is no guarantee of success. This is definitely one that I will keep an eye on.

 

Stem Cell Transplant vs CAR-T, with a Cannoli

If you read the title of this post and are now very confused, I'll explain below. 

But before I get to that, I want to remind everyone to take the Follicular Lymphoma Foundation's annual survey. The survey will be available until October 19, so you only have a few more days from when I am posting this. It's a chance to have your voice heard - the FLF shares results with oncology researchers and clinicians, so together, we can help them understand the things that think are important for them to know about patients. 

The survey is anonymous and shouldn't take more than 10 minutes to complete. Thanks for your help with this.

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Now, about the title of this post:

CancerNetwork is the web site for the medical journal Oncology, and they sponsor a series of recorded debates called CancerNetwork Face-Offs. In these events, cancer experts are divided into two teams. Each team takes one side of a particular controversy in oncology, and makes a presentation about it. The idea is make these events educational, but also "fun" -- as much fun as anyone can have in discussing cancer.

(To be clear, I am all for fun, even in discussing cancer. It's obviously a serious business, but I can appreciate that people who are around cancer patients all day might want to add a little levity to their jobs.)

Part of the fun is in coming up with team names. So, for instance, in one Face-Off, two teams of oncologists from Chicago debate about....well, let me just copy the description at the start of the web page: "Panelists discuss various aspects of lower-risk myelodysplastic syndromes, including trial results on erythropoiesis-stimulating agent timing and novel agents like luspatercept and imetelstat, treatment sequencing and timing debates, personalized approaches based on erythropoietin levels, and complex case management balancing immediate symptom relief with long-term strategies."

The fun part? One team is named after the Chicago Cubs, and the other after the Chicago White Sox, the city's two Major League Baseball teams.  

Now, back once again to the bog post title. Some of these Face-Offs include videos of the debates. But their most recent one included a transcript of the event, with the title "Boston’s Best Did Not 'Leave the Cannoli' in Battle of Lymphoma Top Trials."

This one caught my eye for three reasons. First, it was about Follicualr Lymphoma, at least partially. Second, the oncologists on the panels were all from Dana-Farber Cancer Institute in Boston (the city where I was born and raised). And finally, the teams were named after two well-known pastry shops in Boston, Modern and Mike's. So the "leave the cannoli" is related to the pastry shops, but also is a reference to a famous lime from the movie The Godfather.  It's one of my favorite films. So how could I not write about this?

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That's a long introduction to a post, I know. I suppose you want some details of the actual face-off.

The two teams debated whether or not CAR-T was "better"than Autologous Stem Cell Transplant. It isn't really about these two treatments going head-to-head, but rather about the two teams doing their best to present information in a way that is both fun and informative.

The teams discuss the results of some recent clinical trial updates, look at case studies of patients, and then whether ASCT or CAR-T is better.

First of all, I'm not sure this is a fair fight. The last time I wrote about Stem Cell Transplants in any serious way was almost 10 years ago, and even then, the subject was about whether or not they were still a good option.  And there has been so much progress in FL treatments since then, it's hard to imagine anyone could make a strong case for Auto SCT over CAR-T.

If you're fairly new to all of this, and don't know what a Stem Cell Transplant is, here's a quick description: Patients who receive a Stem Cell Transplant receive very aggressive chemotherapy, aggressive enough that it pretty much destroys their immune system. It can take up to 30 days for the body to recover that system. But that leaves the patients vulnerable to all kinds of problems, since they have no defense against even the weakest virus. So they are given a Stem Cell Transplant, putting immature immune cells into their bodies that can grow into immune cells quickly -- maybe within 7 days -- leaving them much less vulnerable.

There are two types of Stem Cell Transplants. An Autologous STC uses the patients own stem cells. Tey are removed from the body before the patient receives chemo and then put back in after the treatment. An Allogeneic SCT uses immune cells from a donor that are a match. The danger with an Allo STC is that the patient's body can reject someone else's cells. The danger with the Auto STC is that those removed cells might have some cancer in them. Auto STC is considered less aggressive, but Allo STC usually had a greater chance of a cure, when it was successful.

(A Bone Marrow Transplant is very similar to a Stem Cell Transplant. The same dangers apply.) 

You can see how an Auto STC could be compared to CAR-T. They both involve removing immune cells and then putting them back in later. But the CAR-T cells are changed in ways that help them to locate cancer cells and remove them them. The Auto STC cells are just going back to their job of being immune cells - they aren't necessarily targeting cancer cells.

It's an interesting debate overall, even if the Auto STC folks had the harder job.  

And to be clear, Stem Cell Transplants are still used. There's no definitive answer when it comes to Lymphoma treatment. Every patient's needs (including their financial situation) has to play a part in the individual decisions about treatment. CAR-T is great, but it's not the best choice for everyone.

Cancer Nerds will enjoy reading this transcript. And whether or not this is your idea of "fun," it is always interesting to me to see experts delve deeply into a topic, present some interesting data, show how it applies to real people, and help us stay informed.

 

Mental Health Awareness Day

Today is World Mental Health Day. 

I found out about it because a notice popped up on my computer. The notice featured a green ribbon, which is the color for mental health awareness.

Of course, Lymphoma awareness uses a lime green ribbon. But the mental health ribbon looked kind of lime-like on my computer, so I had to look it up and make sure we weren't sharing the same ribbon color. These things are important. (Not really.) 

But when I saw that the two ribbons might be the same color, it seemed very appropriate to me, particularly for Follicular Lymphoma. As I have said for a long time, for many FL patients, the symptoms and side effects of the disease are not physical, but emotional, mental, and spiritual. Lots of us were asymptomatic at diagnosis, and maybe stayed that way for a long time. For me, it was two years of watching and waiting.

But even with no or few physical symptoms, there are plenty of mental ones during that watch and wait period.  (The Follicular Lymphoma Foundation just did a webinar on Watching and Waiting, and of course, issues related to mental health were a major part of of the discussion.) 

And there are plenty of other times during our lives as FL patients when mental health issues are important. Certainly at diagnosis. It's such a surprise for many of us, especially when we're asymptomatic. I've spoken with so many FL patients who say they were in the best shape of their lives when they were diagnosed -- again, myself included. That shock takes some time and effort to deal with. Even those of us who suspected that there was an issue still have the shock of having it conformed. "You have cancer" might be the scariest words in the world, despite all of the advances in cancer research in the last 20 years. 

And then comes treatment, and all of the mental health issues that come with it. Uncertainty over whether it will work, or whether there might have been a better choice. Fear of physical side effects -- still a huge concern for so many patients. And the mental health issues that come with being physically weakened by treatment, and having to worry about finances and every day life.

And then, post-treatment. the fear of recurrence. Even that one is different for us as FL patients. We've been told since diagnosis that the disease is incurable, and chances are good that it will return even after successful treatment. Dealing with that possible return has its own special mental health challenges.

And then, there's the mental health challenge that I think doesn't get talked about enough -- guilt. There's the survivor's guilt of going through treatment. There's the guilt that comes from being in an online group and realizing that others have had it much rougher than you have, and wondering if yu have anything to tell them that's helpful.

I'm not listing all of these mental health challenges because it's in any way fun. 

I'm listing them because I've been through each of them myself.I think there is something very special about reading or hearing about someone else's problems and realizing that you are not alone in having that problem. If, for example, you feel some kind of guilt related to your FL, know that you're not the only one. There's some comfort in that.

Which is ultimately what "awareness" days are about. They're about a collective understanding of something, and hopefully, a collective resolve to do something about it.

The FL Community Podcast's most recent episode is on mental health issues. It's worth listening to; you'll get an even greater sense that you're not alone in feeling what you're feeling.

And remember that if having Follicular Lymphoma gets a little overwhelming sometimes, that's OK. There are places online to have conversations with other FL patients and to get some reassurance. (And I'm always happy to listen, and to offer advice if I'm asked for it. I respond to every email that I receive.) And if talking it through isn't working, talk to your oncologist's office for advice on mental health professionals that might be affiliated with your cancer center. It's ok to seek professional help if that's what you need. 

I hope everyone has a great day today. Do something nice for yourself. 

 

Acalabrutinib + R-Squared for FL

The journal Nature Communications published an article a couple of months ago (I know, I'm behind on things) called "Frontline acalabrutinib, lenalidomide and rituximab for advanced stage follicular lymphoma with high tumor burden: phase II trial." 

It's a follow-up on some research that was presented at the ASH conference in 2023.  

In this study, researchers added Alcalabrutinib (also known as Calquence) to R-Squared. Alcalabrutinib is a BTK inhibitor. Just like other inhibitors, its job is to inhibit, or stop, something from happening -- in this case, Bruton's Tyrosine Kinase, an enzyme that is necessary for B cells to develop. B cells are, of course, the type of immune cell that includes the cells that can lead to Follicular Lymphoma. And that's what happens with a BTK inhibitor. The BTK enzyme does its job too well and won't die off, meaning the B cell won't die, leading to cancer. A BTK inhibitor stops that process and lets the cell die the way it is supposed to. 

Alcalabrutinib is already approved for some other blood cancers -- Chronic Lymphocytic Leukemia (CLL), Mantle Cell Lymphoma (MCL), and Waldenström's macroglobulinaemia.  So it makes sense that researchers are trying it with FL. However, there have also been several other BTK inhibitors that are effective with other blood cancers, but not FL.

The presentation at ASH in 2023 showed that this combination of Alcalabrutinib was very promising. The research is from a phase 2 clinical trial with 24 patients (a pretty small number). The patients had not received any treatment yet. The Overall Response Rate was 100%, and the Complete Response was 92%. After 26 months, 6 patients had their disease progress. The most common serious side effects (grade 3-4) were low neutraphils, a type of white blood cell, 58%, liver function test elevation (17%), infection (12.5%; 2 out of 3 related to COVID19), anemia (8%) and skin rash (8%). 

The Nature article was meant as a follow-up, looking at some longer-term data. The researchers were especially interested in what they call CR30 -- how many patients were able to maintain their Complete Response after 30 months. For them the CR30 rate was 65%. I'm not sure how that compares to some other treatments, but it seems positive. (This is a single-arm study, meaning they didn't split the patients into two groups so they could compare two treatments directly).   

After a median follow-up of 43 months, the median PFS (Progression-Free  Survival) was not reached, meaning more than half of the patients had not progressed. The PFS rate after 2 years was 79%, and for 3 years it was 62%. The POD24 rate was 17%, meaning 17% of patients who had a response had their disease return within 24 months. About 20% of FL patients are POD24, so this seems roughly in line with that number. 

Overall, the numbers look very promising. It will be interesting to see how this goes in a larger phase 3 trial.

I think what's really interesting, though, is the number of articles I've seen recently that look at R-squared triplets -- combinations if Rituxan, Revlimid (Lenalidomide), and something else. It makes sense. R-Squared has been shown to be as effective as traditional chemotherapy, but with a different set of side effects. SO instead of combining a single agent with chemo, researchers are hoping a combination with R-squared will increase effectiveness, hopefully without increasing side effects. That seems to be the case with this triplet, making a BTK inhibitor more effective than it has been on its own.

 Time will tell.