ASCO Preview: Treatment Success and Costs

I have to say, I'm a little disappointed in the Follicular Lymphoma presentations at this year's American Society of Clinical Oncology (ASCO) meeting. As I wrote in my last post, I was hoping that the very low number of abstracts (only 20) when they were first released was going to rise as more were added online. But it hasn't. There's just not a lot of research on FL at this year's conference.

I tried to look on Twitter/X to see if there was anything that Lymphoma specialists were excited about. Not so far, at least not for FL. Right now, with the meeting starting tomorrow, there are a lot of oncologists posting selfies in airports, saying how excited they are about heading to Chicago. Good for them -- I always like to see oncologists that are excited about learning new things. It's a medical specialty with high burnout rates, and a get-together like this is good for them. If you have an appointment in the next month, maybe you'll notice a little more happy bounce from your doctor.  (My own oncologist, Dr. H, is part of groups making two presentations. I hope it's good for him.)

But all of that means that, at least for now, there are limited things to write about. I'm hoping in the next few days, as the research is actually presented, there will be some excitement online, and then in the next few weeks, we'll see more of that excitement as oncology websites post videos of Lymphoma specialists being excited. 

So what I'd like to share for now (in the absence of al of that excitement) is "Real-world evaluation of treatment pattern, time to next treatment (TTNT), healthcare resource utilization (HCRU), and cost of care in follicular lymphoma (FL)." As I said in my last post, there is a kind of theme in the small number of abstracts this year on "real world" data -- what happens after clinical trials are over and a treatment has been approved. 

This research looks at data related to measuring treatments in a few different ways. The researchers look at data on almost 6000 FL patients who had treatment for FL between 2019 and 2023. The researchers broke them into groups based on which line of treatment they had received -- first line, or 1L, were receiving treatment for the first time, and then 2L, 3L, and 4L had refractory or relapsed disease (their treatment stopped working or didn't work at all and so they received another line of treatment). The researchers were interested in Time To Next Treatment (TTNT) -- basically, how long a treatment works.

They were also interested in cost. A treatment that costs a lot might be justified if it works for a long time -- long enough that another treatment (and its cost) isn't necessary. In the same way, a less expensive treatment might not be justified if it doesn't last long, and a costlier treatment is necessary sooner.

It's important to point out that this research was sponsored by a pharmaceutical company. Its particular treatment, a BTK Inhibitor, is not included directly in the data, but it certainly has a stake in presenting data that favors its business. (I'm not saying they are falsifying data or anything like that. It certainly seems legitimate. But they could have chosen to not present it at all if it didn't ultimately help them.)

So, as for the results.

For first-line treatment, the most commonly used was Rituxan on its own (32% of patients in the study), followed by Bendamustine-R (27%) and then R-CHOP (22%). I find this kind of interesting in and of itself.  The Rituxan number seems higher than I have seen before. And the two traditional chemotherapies making up about half of all treatments shows that it is still very much in use, despite all of the other options that have been approved. (Important to remember that many approvals are for 3L and 4L, of course). That same order was true for second-line treatment, too. For third line, things change -- R-Squared (Rituxan + Revlimid) was most popular, Obinutuzumab is mor frequently used in place of Rituxan, and "Others" become increasingly more common than Rituxan, R-squared, or chemo combinations. All of this makes sense -- approved, well-known treatments are used first, and then less common (sometimes still in trials) treatments are used as the others stop working. 

Time To Next Treatment (TTNT) decreased with each line, no matter what the treatment. This makes sense, too. I remember being told, 16 years ago, that it was common for FL to take this path. I was told I'd likely need multiple treatments, and with each one, my FL would get more aggressive and the TTNT would get shorter. I don't think that's necessarily how it works for everyone these days -- treatments are getting better and more effective, and it seems like more patients are hitting on a treatment in 2L or 3L that gives them a longer remission. But this data confirms that, for those who do need multiple lines of treatment (that is, those who have a more aggressive type of FL), TTNT is smaller with each line.

Their data on cost is also interesting. The mean total cost of treatment (the treatment itself, the cost of a doctor's visit, etc.) ranged from $40,538 to $74,466, with the cost going up with each line. The mean total cost of care was consistently lowest with Rituxan on its own ($31,704 to $36,197), and highest with CAR-T ($501,493 to $522,378). Again, none of this is a surprise. More common treatments tend to cost less money, and less common ones tend to cost more.

The conclusion that the researchers came to was that things were tougher for FL patients as they had more lines of therapy -- treatments don't last as long, meaning greater financial costs, but also greater physical and emotional costs. They say "These findings suggest the need for better treatment options for patients with FL, especially in 3L and 4L." 

I don't think anyone is going to argue with that conclusion.  We've known for a very long time that patients have greater needs as treatments stop working. But it also helps justify approving and using a new BTK Inhibitor, should one become available. (And that's not a criticism of the sponsor of the research -- it just shows that there is a need that they are hoping to fill. It's data that confirms what we already know.)

So I'll keep reading and watching and listening, and hope that something very exciting pops up soon, as oncologists start to attend sessions at ASCO. It's all still very exciting to me, regardless.

ASCO Abstracts!

The ASCO Abstracts are finally available!

If you've been reading the blog for a few years, you know how much I love this time of year. The ASCO conference (the annual meeting of the American Society for Clinical Oncology) starts next week. It's the largest gathering of oncologists in the country, and the place where many researchers try to present their findings, knowing they will have a large potential audience.

Before the conference begins, the abstracts are released. It's like Christmas for Cancer Nerds -- those who are planning to attend can read summaries of the research and decide which presentations they want to go to. As I have said, I've never been able to attend an ASCO in person (it's never a good time of year for me), but ASCO allows to patient advocates to see some extra stuff online, so I'm looking forward to a deep dive.

So far, there are only 20 abstracts available when I search for "Follicular Lymphoma," which is fewer than usual. However, the email announcement that I got last night said that "over half" of the abstracts are now available, so I suspect a few more will trickle in soon.

Twenty isn't a lot, but I can see a couple of trends already.

First, there are three abstracts for Odronextamab. This is the bi-specific that was denied approval a couple of months ago by the FDA, but only because they didn't have enough data yet, not because of safety or effectiveness issues. The three abstracts look at data from three different trials -- one comparing Odronextamab + chemo with Rituxan + chemo in previously untreated FL; another that looks at Odronextamab on its own in previously untreated FL; and a third that looks at Odronextamab + Lenalidomide compared to Rituxan + Lenalidomide (R-Squared) in refractory/relapsed FL. They're certainly testing it in lots of different situations.

Similarly, there are several abstracts for Epcoritamab, another bispecific. It has already been approved in the U.S. and Europe for aggressive lymphomas, and it got quite a bit of attention at the ASH conference in December.  Same with ASCO, with several more abstracts looking at its effectiveness in combination with other treatments for FL.

Finally, one more trend -- a bunch of "real world" studies. These are research studies, usually from just one cancer center, that happen after a treatment has been approved. The idea is that a clinical trial usually limits who can participate. For example, it might not allow patients with heart disease in the trial, since that would make it harder to tell if the treatment being tested has caused heart damage. It makes sense. But a "real world" trial doesn't have so many restrictions. The researchers want to know what happens to everyone who has the treatment, not just the group that was allowed in the trial. There seem to be a larger-than-usual number of presentations with "real world" in their titles. That could be that there are fewer overall, so they stand out more. Or it could be that there are more treatments being approved that can now be studies outside of trials. Either way, real world studies tell us more about how a treatment actually works.

One thing that also stands out is how few CAR-T presentations there are. We may see more of them in the next week, as the rest of the abstracts come in. It's important to keep in mind that what's available so far isn't what's hot or popular; if anything, it means the people reporting on the research are earlier. (Presentations about active trials, for example, might wait until the last minute to make sure they have as much data as possible. Real world studies don't have the same urgency, since they're reporting on a treatment that has already been approved. They don't need up-to-the-minute data.)

In addition to FL presentations, I'll look at some of the other research out there, especially things dealing with survivorship and quality of life, which have become more important to me lately.

Check back soon. And if there's something super-exciting that has the whole meeting abuzz, I'll get that out right away.

CAR-T Approval by FDA

Last week, the FDA granted accelerated approval to Breyanzi, also known as lisocabtagene maraleucel or Liso-cel, to patients with relapsed or refractory Follicular Lymphoma who have received two or more prior systemic treatments. Liso-cel is a type of CAR-T. This is great news for many of us, since it makes the treatment available to lots of patients.

Some background first. CAR-T is not a single treatment (even though I know I am guilty of writing about it as if it were). It' a broader category, like chemotherapy or immunotherapy, with lots of different options under that umbrella. So there are a few different versions of CAR-T that have been approved for different cancers, and many more in different stages of development. But they all work in basically the same way -- T cells, a type of immune cell, are removed from the patient's body, manipulated in a lab so they recognize cancer cells, and are then put back into the patient to do their job. 

Liso-cel had already been approved for some aggressive blood cancers, including FL grade 3b, which is an especially aggressive type. But now it is approved for more FL patients, those with r/r disease (their last treatment stopped working, r didn't work at all) who have had at least two other treatments. 

The approval is based on a phase 2 clinical trial called TRANSCEND-FL. Like other accelerated approvals, this one is not based on a large phase 3 trial, but rather the smaller phase 2. Despite that, there seem to be fewer concerns about safety than with other trials, since Liso-cel has already been approved for other cancers, and safety issues are fairly well-known by now,

The phase 2 trial was very successful -- the Overall Response Rate was 95.7% in 94 patients, and after a median follow-up of 16.8 months, the median durability of response hadn't been reached (meaning more than half of the patients still had a response to the treatment). 

Safety was not a concern, in that there were not any new side effects. The most common were cytokine release syndrome (CRS), headache, musculoskeletal pain, fatigue, constipation, and fever. The approval included a "Risk Evaluation and Mitigation Strategy" for Liso-cel, meaning they recognized the potential seriousness of CRS and nerve problems, and made sure there was a plan to deal with any patients who showed signs of them before they became serious. And that includes the "black box warning" that has already been required. 

So, as I said, all of this is great news for FL patients. Even for those of us who do not qualify (including me), it shows that CAR-T is effective for more and more of us. We're waiting on more trial results for CAR-T treatments for other FL populations, including those who need a first-line treatment. Maybe we'll get an update in a few weeks at ASCO. 

Speaking of ASCO -- for those who don't know, this is the American Society for Clinical Oncology, and their annual meeting happens in early June -- I'm still waiting for them to release their abstracts so I can see what kind of research will be presented. I was once again allowed to register for free as an independent cancer advocate, which means I'll have access to more information that usual. Not everything, but lots of things. I'm looking forward to sharing what I learn. And a big THANK YOU to ASCO for allowing independent advocates like me to participate in this way. Not every medical organization is so generous.

More reasons for hope, coming soon. 

 

Cancer Newsletter

I spend a  lot of time reading about cancer, as you probably know (or you can probably tell). 

I get lots of stuff in my email inbox about cancer, some of which I asked for, and some of which I did not. (I was contacted by a public relations aggregator years ago. They send press releases to journalists and bloggers, and they asked if I wanted to be included. I said yes, so about 20 times a day I get an email from someone pushing a product or a story related to "health" in some way. Very occasionally, it's something useful. Mostly it isn't anything that I want to write about. But I do enjoy knowing what is being pushed when it comes to "health."

One thing that I did receive that has been useful and interesting is a newsletter called Breaking Cancer News. That title sounds fake, to be honest. I fully expected it to be a newsletter full of stories about one product that was really questionable. But the first time I received it, I spotted a name that let me know it was legitimate. 

The name was Jamie Reno, who is the editor of the newsletter. He's also a long-time journalist who used to write for Newsweek and Healthline and a whole lot of other publications. I know the name because he has also been diagnosed with Follicular Lymphoma about 22 years ago. He wrote a book called Hope Begins in the Dark, which tells the story of 50 patients who were diagnosed with Lymphoma. And if my memory is correct, he was an early user of RadioImmunoTherapy (RIT).

So if it's cancer-related, and Jamie Reno's name is on it, I feel like I can trust it.

I signed up to get Breaking Cancer News sent to me once a week, and I am enjoying it (as much as someone can enjoy reading about cancer). The stories are written with a general audience in mind, so they're easy to understand (unlike most of the stuff I link to in this blog). And the stories deal with current issues, as the name of the newsletter suggests. Not necessarily about things like FDA approvals or clinical trials. More about issues that affect all patients, caregivers, and advocates.  

For example, in this week's issue, there's a short commentary from Jamie Reno about how politics is keeping a cancer funding initiative from being passed in Congress. Then there's a story on multi-drug resistance -- how cancer cells can find ways to survive multiple treatments, and what researchers are trying to do about it. And finally there's a story on some of the latest developments in cancer prevention and detection. 

None of this is about Follicular Lymphoma, specifically, but it does provide some interesting context on the larger issues that affect cancer patients and researchers. I like the big picture it provides me.

The header on the newsletter says it was developed in partnership with the organization Teen Cancer America, which focuses on helping young people who have been diagnosed. And the newsletter's tag line is "Plain talk about what's hot and hopeful in the cancer arena -- for young people and anyone else who's listening." But don't be fooled -- there's good stuff in there for all of us.

I don't have any affiliation with the newsletter or the organization that sponsors it. I've been reading it for a few months now, and it seemed like something worth sharing. I hope you'll find it interesting.

Improved Outcomes for Transformed FL

The journal Cancer Medicine  published a very interesting article lest month called "Outcomes of the transformation of follicular lymphoma to diffuse large B-cell lymphoma in the rituximab era: A population-based study." It describes a large research study that compared the outcomes for patients who were diagnosed with Diffuse Large B Cell Lymphoma (DLBCL), an aggressive type of Lymphoma, with those who were diagnosed first with Follicular Lymphoma and whose disease then transformed to DLBCL. There's lots of interesting data here, but the most important is this -- in the last 20 years, outcomes for FL patients with transformed lymphoma are greatly improved.

It is important to note that this is a "population study," meaning the researchers didn't look at individual patients. Instead, they looked at a large database called the SEER (Surveillance, Epidemiology, and End Results). You're probably in it -- oncologists upload anonymous data into the SEER database so this kind of large study can be done. Population study look at trends, rather than individual patients. But because they are looking at large numbers of patients, the results can be very interesting.

For this study, the researchers were interested in patients with transformed FL who were diagnosed between 2000 and 2020. This time period is known as "The Rituxan Era." Rituxan was approved by the FDA in 1997, and there were big improvements in FL patient outcomes once Rituxan started getting mixed with traditional chemo, and then with other treatments. As the researchers note, small studies focused on transformed FL are inconsistent in what they reveal, so they thought a large study like this would be helpful.

And it is indeed large. The researchers found 50,332 FL patients in the database who were diagnosed in that 20 year period, along with 95,933 patients who were diagnosed with primary DLBCL (in other words, they didn't have FL first). Of those 50,000+ FL patients, 1631 had disease that transformed. 

That in itself is very significant to me. When I was diagnosed (in 2007), I read in many places that as many as 50% of FL patients would end up with transformed disease, which was alarming to me. Over time, in the small studies that I read, the numbers would usually come as closer to 15 or 20%. That's slightly less worrisome. But in this large study, only 3.2% of FL patients transformed to DLBCL. That is, obviously, a significantly smaller number. 

(I'm not suggesting the old research was wrong, or the new research is wrong, or that transformation is no longer a big deal. Just that the smaller number is very surprising to me.)

In fact, it's important to note that one of the things the researchers make clear is that transformation has a serious impact on Overall Survival. For patients with transformed disease, the OS rate at 10 years was 56.6%, with a median survival of 137 months (a little over 11 years), with a range of 2 months to 21 years. For patients who did not have transformed disease, the 10 year OS was 64.8%,  with a median survival of 194 months (about 16 years), with the same range of 2 months to 21 years. So clearly, transformation is still a big deal.

But the larger point they're trying to make still holds true --  compared to the time before Rituxan, outcomes for transformed FL are better. 

A few other interesting bits:

• Patients who had received Radiotherapy or who Watched and Waited had better outcome after transformation than those who received traditional chemotherapy or a combination of chemo and radiation. (they don't get into why this might be so, but my guess is that it has less to do with the treatment itself and more to do with how aggressive the disease was before transformation. FL patients who watch and wait tend to have less aggressive disease; those who get chemo tend to have more aggressive disease. All of that is entirely my own, non-expert guess.)
• Patients whose disease transformed soon after their FL diagnosis (within 18 months) tended to do better than those with later transformation (after 18 months). I wonder if this had to do more with how long it took to discover the transformation, rather than the actual transformation. Again -- my non-expert guess.
  
• There are more options now for treating transformed FL, obviously. The recommendation used to be a Stem Cell Transplant. That's still an option, but no longer automatic, especially as more FL patients have traditional chemo "reserved" as a later possibility.

It's fascinating to me that, even 16 years after I was first diagnosed, we still have lots of unanswered questions about transformation -- and about so many other aspects of Follicular Lymphoma.  But despite the lack of answers, we are still seeing overall improvement as a group. And that's worth celebrating.

Patient-Derived Lymphoma Spheroids

That post title is a lot, but it's the subject of some very cool recent research on Follicular Lymphoma that might be a big help to us someday.

The Blood Cancer Journal just published an article called "Patient-Derived Follicular Lymphoma Spheroids Recapitulate Lymph Node Signaling and Immune Profile Uncovering Galectin-9 as a Novel Immunotherapeutic Target." There's a lot of science in that title, and even more in the article, but as I said, it's very cool research.

The article describes the use of something called a Lymphoma Spheroid. As the "sphere" in the name implies, it's kind of a ball of lymphoma cells plus some other things. And here's why it's important.

Before a cancer treatment can be tried out on people in a phase 1 trial, it needs to go through a whole bunch of "pre-clinical" steps. After a possible treatment is developed (and there's whole bunch of steps to go through with that, but that's another post), the next step is come up with a target for treatment, and then figure out if the new treatment will work on that target. This is usually done "in a test tube," mixing the treatment with some cancer cells.

But it's much more complicated than that. Think about it -- if I put some cancer cells in a test tub and then added some gasoline, the gasoline would almost certainly kill the cancer cells. But that's not helpful -- you wouldn't want to put gasoline into your body. It would kill all of your cells, not just your cancer cells. So you need a treatment that will work on the cancer cells but do minimal damage to healthy cells. That's a little bit more of a challenge.

Even then, it gets complicated. A treatment can work fine in a test tube, but then fail when it's given an actual patient. Why? A big reason is the microenvironment for the cell. This is everything that physically surrounds the cell. And the microenvironment plays a huge role in cancer cells surviving. People (you may have noticed) are not just individual cells; we are complex systems. Change one thing in a person, and you're likely to change a bunch of other things. You bang your toe, and soon your back hurts, because you're walking differently. With a sore back, you don't sleep well. Without sleep, you need more coffee. This makes you jumpy and you can't sit for long. this makes your sore back worse. 

You get the idea. Works the same for cancer cells. You try to kill a cancer cell, and something else gets in the way -- an immune cell, an enzyme, a protein. If it was easy to kill cancer cells, you wouldn't be here reading this.

The idea of a Lymphoma Spheroid is an attempt to deal with this challenge. It's been around for a few years, with some interesting research already being done with it.

Rather than just putting an FL cell in a test tube, the Patient-derived Lymphoma Spheroid attempt to create a 3D model of what's happening in the body -- recreating as best it can the microenvironment that the FL cell exists in. The researchers mixed together a formula with about 60% tumor B cells, and then added about 13% T cells that have the CD4 protein, and another 3% that have CD8. The researchers found that this mix kind of organizes itself into something that resembles what's happening in the patient's body, with the spheroid doing things like producing things like PD1 and CD3 that are already targets for treatments.

Just as important, it's showing that there are new targets for Lymphoma researchers to create treatments for, like CD39, a protein on the surface of the cancer cell. Some other research found that Obinutuzumab and Nivolumab, an anti-PD1 treatment, might be effective. 

The article from this week used Patient-Derived Lymphoma Spheroids to show that a protein called galectin-9 can lessen the effectiveness of Rituxan, and so they are proposing that galectin-9 would be a good target for future treatments. 

The most important thing with all of this is not just the "Lymphoma Spheroid" part of it, but the "Patient-Derived" part. Follicular Lymphoma is heterogeneous -- it shows up in very different ways for different patients. That's why there is no real agreement on what the best way to treat it is. But the Patient-Derived Lymphoma Spheroid takes cells from each patient. In other words, this isn't an attempt to study how FL behaves. It's an attempt to study how your FL behaves. We're all different, so recreating your personal microenvironment should, at least in theory, tell your doctor which treatments are likely to work best for you. that's what "personalized medicine" is all about.

Will this ultimately change things? Hard to say. Lots of cool things turn out to work less effectively than we'd hoped, once they get tested out on a large group of patients. But there's already a growing body of research that is showing some success. Time will tell.

But for me, getting (and sharing) a little bit more insight into the process for developing treatments is also the cool part. I often see (and share) research that is much farther along, and the closer it gets to the doctor's office, the more exciting it is. But there is a whole lot of work that goes into that journey from a test tube in a lab to an intravenous tube in a treatment room, and I like the reminder of that.

More good stuff to come. The ASCO abstracts are due out very soon....