ASH Review: MedScape on R/R FL

I'm still sifting through some of the commentaries that people are posting about what they saw and learned about Follicular Lymphoma at the ASH meeting. Today's commentary is a video, posted by the website MedScape, called "Charting New Horizons: Emerging Data and Novel Therapies in Relapsed/Refractory Follicular Lymphoma."

I guess it's technically a video, since it's posted on YouTube. But really, it's more like a podcast -- audio commentary without any real visual element. There is the option of seeing a transcript. You'll find a button in the description box below the video.

The post features two Lymphoma experts, Dr. Lori Sen from the University of British Columbia, and Dr. Cammy Maddox from Ohio State University. Their focus is on presentations from ASH that present data from studies on Relapsed and Refractory Follicular Lymphoma.

Of course, the first one they describe is the one that everyone is talking about: Tafasitamab and R-Squared. I've seen it called a "triumph" and a "practice-changer." Dr. Sen and Dr. Maddox seem equally impressed. They point out that the study was very wide, taking place in multiple countries. It was double-blind, meaning there was a direct comparison between two treatments. It had excellent results and good safety. And it showed that it is possible to combine two monoclonal antibodies -- one that targets CD 19 and one that targets CD20 -- and have good effectiveness and safety. I have to say, the more I read about it, the more impressed I am. I'm still not sure it will be the "game-changer" that some seem to think it will be. But that's  more about asking oncologists to break old habits than anything about how good the treatment is. 

The next presentation they describe is "337 Loncastuximab Tesirine with Rituximab Induces Robust and Durable Complete Metabolic Responses in High-Risk Relapsed/Refractory Follicular Lymphoma." Loncastuximab is an antibody conjugate. Basically, it's like Rituxan, targeting a protein on the surface of the lymphoma cell (CD19), but attached to it is a small drop of a chemotherapy drug. This allows the chemo to go directly to the cancer cell. In theory, this results in fewer side effects and better effectiveness. The Overall Response Rate was  97.1% after 12 weeks, with a Complete Response of 68.6%. For the FL patients in the study, the ORR was 100% and the Cr was 80%. Safety was good. A wider study is ongoing, so we may hear more about this one soon. 

The next presentation they look at is Epcoritimab with R-Squared, another one that has gotten lots of commentary since the meeting ended. I was curious about what they had to say about the possible safety issues with this treatment combination. They do mention that the study happened during the Covid pandemic, which likely affected things negatively (since the combination would affect immunity). There were no new side effects -- nothing unexpected. 

They finish by talking about how the data will affect clinical practice. Again, Tafasitamab and R-Squared have a prominent place here. In general, they seem to agree that the various presentations at ASH that excited them most are more proof that we are moving away from traditional chemotherapy and towards treatments that involve the immune system and that target lymphoma cells specifically. This has certainly been the trend for a while, and it's a good thing. They also agree that using these newer treatments effectively takes some learning on the part of oncologists. They will require active surveillance of side effects so things like Cytokine Release Syndrome don't become too dangerous.

It's an interesting video/audio, and it reaffirms a lot of what I've been reading and hearing so far.

Still a few more commentaries to sift through. If there's something good in them, I'll be sure to share.

ASH Review: 5 Year Follow-Up for CAR-T

Continuing our look at what Lymphoma experts have to say about presentations at ASH a couple of weeks ago. I'm seeing lots and lots of commentary about Tafasitamab + R-Squared (the excitement was there even before the ASH meeting began, so no surprise there).

One commetary caught my eye this morning. It's from the lead researcher for abstract #864, "5-Year Follow-up Analysis from ZUMA-5: A Phase 2 Trial of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma." 

The commentary is from an article website Health Day, and features a video (with written transcript) from a Leukemia specialist and a Lymphoma specialist.  The Lymphoma specialist is Dr. Sattva Neelapu from MD Anderson, who discusses the abstract above.

The presentation looks at data from the ZUMA-5 trial. There are a series of ZUMA trials, each looking at the CAR-T known as Axi-cel or Yescarta, but looking at the effects from different patient populations. ZUMA-5 focuses on patients with indolent NHL, including Follicular Lymphoma, who had relapsed or refractory disease. The ZUMA-5 trial actually resulted in Axi-cel being approved for R/R FL in 2021, so this research isn't about trying to show the FDA that it is safe and effective. We already knew that.

Instead, this presentation is meant to show that Axi-cel remains safe and effective. 

The study involved 159 patients, with 127 of them having been diagnosed with Follicular Lymphoma. The patients in the study had already received at least two other treatments, including immuno-chemotherapy (like R-CHOP or B-R). This presentation looks at what happened to the patients after 5 years. 

In the video, Dr. Neelapu says the Overall Response Rate was 90% and the Complete Response Rate was 75% -- even higher in patients with Follicular Lymphoma at 79%.

The median Duration of Response -- how long it kept the cancer away -- was a median of 60.4 months, or a little over 5 years. (Median means half had a longer response and half had a shorter response).

Among patients who achieved a CR, 58% remained in response after 5 years. The Progression Free Survival rate was similar at 50.4%. For patients with a Partial Response, the PFS was 6.9 months. The median Overall Survival was not reached. To get a median, you need half of the patients to have died, so after 5 years, more than half were still alive -- the researchers estimated 69% of the patients were still alive after 5 years.

Among patients with Follicualr Lymphoma, the OS was estimated at about 65%, meaning 35% of the patients had died, whether from disease progression or from some other cause. These other causes included some secondary cancers and infections, as well as non-cancer-related causes.

I their conclusion to the abstract, and in the video, the researchers say that the results show that Axi-cel may have the potential to be a cure for a certain subset of patients.

I have a couple of thoughts.

First, looking at the numbers, it's clear that CAR-T is improving. The early results from CAR-T showed that roughly 33% of patients had a long duration of response, 33% had a duration of about a year, and 33% did not respond at all. The numbers here after 5 years are a lot better. CAR-T is working, and after some time, oncologists are getting better at dealing with side effects and with identifying who will be helped by CAR-T. 

Second, that word "cure." It's a funny word when it comes to Follicular Lymphoma. Clearly, CAR-T was not a cure for a whole lot of patients in the study. But clearly, it has been a huge help to a whole lot of others. The problem with using that word is that "cure" is hard to measure. In other cancers, the 5 year mark is often used to declare someone as "cured." But FL has a habit of coming back even after 5 years, at least for some people. 

But many oncologists use the term "functional cure." If an FL patient is diagnosed at a later age and has a treatment that lasts for as long as they live, we can call that "cured." And for others, the disease may return, but in a less-aggressive way that doesn't require treatment. That makes them "cured," in a sense.

Many FL patients use the phrase "Dying with the disease, not from the disease." And that amounts to a "cure" in a way, too.

I have my own issues with the word "cure," obviously, and I may write more about that sometime soon. But for now, we at least agree that for many patients, Axi-cel CAR-T has been very successful.

I'm still sifting through some other post-ASH commentaries. I'll share more soon.

ASH Review: Epcoritimab + R-Squared

 OK, SH is over, and it's time to continue to look at some of the presentations that made some noise. We already looked at some of the FL presentations that got some attention (those presentations on diet and blood cancer had some people talking on Twitter/X). 

So now it's time to look at the presentations that are getting attention after the meeting is over. 

Let me first respond to a comment from a reader named Peter, who wrote about my post on the "triumph" of Tasafitamab. He wrote "I’m always a bit skeptical of headlines that use superlatives (like “triumph”), especially when they’re from less scientifically rigorous sources (like fiercepharma)....A good mantra I learned to repeat to myself, back when I was first getting diagnosed and learning about lymphoma, is “if something sounds too good to be true, it probably is”. I found it the best way to try to control my own confirmation bias."

Amen to that. And it is with Peter's words echoing that I present to you "342 Fixed-Duration Epcoritamab + R² Drives Deep and Durable Responses in Patients with Relapsed or Refractory Follicular Lymphoma: 2-Year Follow-up from Arm 2 of the Epcore NHL-2 Trial." 

This presentation looks at data from a phase 1b/2 clinical trial. (This means they have combined the phase 1 study, which focuses on safety, and the phase 2 study, which focuses on effectiveness -- they use many of the same patients rather than having to start a whole new trial). There were 111 patients in the trial, and they received the bispecific antibody Epcoritamab as well as the combination R-Squared (Rituxan + Revlimid, also known as Ledalidomide). The patients all had relapsed or refractory disease (their last treatment didn't work or had stopped working). 

The results were very good -- the patients had an Overall Response Rate of 96%, and a Complete Response Rate of 87%. That's pretty great. The treatment worked well no matter what the patients' treatment history was. Patients with POD24 had a CRR of 79%, for example. After a median follow up of 24 months, an estimated 69% of patients were still responding to the treatment, and 75% of those with a Complete Response had maintained their Complete Response.

The researchers note that the study took place during the Covid pandemic, and 57% of patients reported getting Covid at some point, resulting in a number of health problems, though there were no Covid-related decisions to stop Epcoritamab.  The most common side effects were were neutropenia (62%) and Cytokine Release Syndrome (51%). At a median of 25.3 months, 17 patients (15%) were still on the treatment; 41 patients (37%) had completed treatment as it was described in the study description; and 53 (48%) had stopped treatment for several reasons: 18 of them had their disease progress, 22 had severe side effects, 7 withdrew from the study on their own, 1 died, one left because of Covid, and 4 left becuase of a doctor's decision.

So why the "If it's too good to be true, it probably is" attitude? 

A lot of the post-meeting analysis will come in the next few weeks or months, at least from oncologists and oncology-focused web sites. The more immediate analysis come from other web sites, and that's where almost all of the news that I got about this presentation came from, namely, finance and investment web sites.

In other words, at least immediately after the ASH meeting, the folks who are most excited about this are the ones who will make some money off of it. 

I've struggled with this for years, and in the United States, we're in the middle of a very controversial situation that is related to it. I won't get into that, because I don't think I can describe my feelings about it very well. 

But I also have to have a little skepticism about the excitement that a new treatment regiment is generating based mostly on a press release from the company that has developed it. It might very well be one of the ASH presentations that oncologists are excited about, and that they'll discuss elsewhere. But I'm going to hold off on my excitement until then, especially given that almost half of the trial participants dropped out before they finished. In their abstract conclusion, the researchers point out that there are no new side effects, compared to the Epcoritamab trial that resulted in its being approved for FL by the FDA and the EU. (And despite there being some safety concerns about Epcoritamab, too.) A few people are talking about it online, but no one is really bursting with excitement.

The clinical trial had a few arms, so there were patients who received Epcoritamab and B-R, for example. It will be interesting to see what oncologists have to say about all of it in the next few weeks and months. I'll keep you posted.

In the meantime, be the good critical thinkers that you are. Stay hopeful, but realistic.

ASH Preview: Practice Changers?

The ASH conference is in full swing today, so I won't be calling my ASH posts "previews" after this. But I'll do it once more in looking at an article from Oncology News Central that was published earlier this week. 

It's really easy to get excited about a conference presentation, and even easier to get excited about an abstract. the presentation itself might last an hour, and involve more detail and some audience questions. the abstract is just the summary -- the good stuff. As Dr. Leonard points out in his Leonard List podcast, that can leave out a lot of the complications that can make it a little less exciting.

And then there's the place that a conference presentation has in the whole life cycle of a research project. The best look at research comes from a publication in a medical journal. That's where it will be peer-reviewed -- other experts in the subject will look it over and point out problems and ask for changes, and if it looks good after that, it will be published. A conference presentation doesn't go through all of that review.

My point is, remember that my ASH previews, that look at abstracts, are only the first step in a long process. The things I look at here -- and that I get excited about -- won't necessarily make their way to the doctor's office any time soon, if they do at all.

Which is why the article from Oncology News Central is so interesting. 

It asks the question, "What Blood Cancer Advances Could Change Practice?" In other words, which presentations at ASH really will end up in the doctor's office some day? They asked some blood cancer experts which abstracts could be important enough to change the way blood cancer patients are treated in the future.

Follicularr Lymphoma makes an appearance. they asked Dr. Cunthia Dunbar from the National Institues of Health, who also serves as Secretary of ASH. One of her picks is "LBA-1 Tafasitamab Plus Lenalidomide and Rituximab for Relapsed or Refractory Follicular Lymphoma: Results from a Phase 3 Study (inMIND)." It's the late-breaking abstract that I wrote about a couple of weeks ago, looking at Tafasitamab added to R Squared. As I said then, "I'm guessing this is going to be the Big Story about Follicular Lymphoma when the ASH conference is over, and we'll be hearing more excitement about it from the experts who give their opinions about things." So we're getting some of the excitement a little early.

Dr. Dunbar says “Tumor cells can evolve to escape targeted therapies via loss of a single target molecule, such as CD20. This approach of using two antibodies simultaneously aims to prevent this escape, resulting in better outcomes.”

That's the only abstract that deals directly with FL to make the list in this article. But there are a few others that get at Quality of Life issues that are worth looking at. The article has a section called "Diet and Lifestyle Focus “Bold and Different” From Previous ASH Meetings." A couple of abstracts look at the influence of higher fiber intake after Stem Cell Transplant, with the idea that they may improve gut bacteria in positive ways. Another looks at a ketogenic diet–derived metabolite that might have the potential to help CAR T be more effective.

I know there's a lot of interest among many FL patients for things like dietary changes that could help us. To be very clear, all of these studies are in very early stages. They are discussed in the article by Dr. Mikkael Sekeres of the University of Miami (a Lymphoma Rock Star, to be sure). But he cautions, "We need to wait for clinical trials before we recommend more restrictive diets whole hog."

You'll notice I have not linked to those studies directly. You can find links in the Oncology News Central article if you want to take a look.  But I'm going to make you work for it. Consider it symbolic -- we often look for quick answers when it comes to things like lifestyle changes to help our cancer.  But they're never that quick and easy. So if you want to read more about them, you'll need to work for it. 

And keep in mind that these abstracts aren't saying that a high fiber or keto diet will cure your cancer. They're looking at how dietary choices may influence how well a specific treatment works. that's a very different thing.

Still, I look forward to seeing the reactions to ASH. I'll share them as they come about over the next few days and weeks.

 

ASH Preview: The Leonard List 2024

I'm doing another ASH post, this time looking at several ASH presentations at once. I'll look at them through the lens of the Leonard List.

The Leonard List comes from Dr. John Leonard of Weill Cornell Medicine. Dr. Leonard is one of the best-known Lymphoma specialists in the U.S., and every year he publishes his List of the 10 most interesting abstracts from ASH, about a week or so before the meeting happens. He discusses them, plus a few bonus ones, on the "CancerCast" podcast from Weill Cornell. You can listen to the full podcast episode here; there's also a transcript if you want to read along or translate it more easily.

I always enjoy listening to Dr. Leonard go through his list, especially when I have already written about something that he finds interesting. I will only focus on his choices that are related to Follicular Lymphoma, but if you are interested in other types of blood cancer, I encourage you to listen to or read the whole podcast for some other great commentary.

The first time FL makes the lost is at number 7, and it actually shows up twice -- Dr. Leonard lists two related abstracts as 7A and 7B on his list.

7A is  "3749 Subsequent Primary Malignancies in Patients with Indolent B Cell Non-Hodgkin Lymphoma Receiving Frontline Bendamustine Rituximab Therapy.” In this presentation, the researchers look at the records of 6284 patients with slow-growing lymphoma (inlcuding FL, but some others, too) who received Bendamustine as their first treatment. They were interested in how many patients went on to develop another cancer after the treatment. According to their research, about 15% of them developed a second cancer, with a median time to diagnosis of 2.36 years, including lung cancer, digestive system cancer, and other blood cancers. Did the Bendamustine cause the other cancers? It's hard to say, as Dr. Leonard says, since many of the patients went on to other treatments, including radiation and Stem Cell Transplants, or simply have immune systems that make them susceptible to other cancers. The takeaway, says Dr. Leonard, is not that Bendamustine is bad or that one treatment is better than another. "To me, the takeaway here is that patients need to be monitored for other cancer. And I think that that is a really important issue for all lymphoma patients. You have to think about lung cancers and GI cancers and monitor for blood cancers, breast cancer, et cetera. And so to me, the takeaway actionable item here is really just to make sure that patients are followed and get the appropriate cancer-related screenings because they are at risk for other cancers." That's an important distinction. We're all at higher risk for other cancers; the scar on my scalp is a reminder of that. Be sure to keep up with cancer screenings.

7B is related: "3009 Impact of Prior Bendamustine Exposure on Bispecific Antibody Treatment Outcomes in Patients with Relapsed/Refractory Follicular Lymphoma." This one looks at FL patients, specifically, who have had Bendamustine, and the went to receive a bispecific antibody. Since Bendamustine can affect T cells, and bispecifics work by engaging T cells to go after the cancer cells, the researchers wanted to know if receiving Benda would make the bispecifics less effective. This is tough, as Dr. Leonard points out, becuase there can be lots of reasons why a treatment doesn't work, and like 7A on the list, lots of patients in this study received other treatments besides Benda. No matter -- the patients in the study didn't seem worse off than other patients receiving Benda when they went on to receive a bispecific. By the time most patients receive a bispecific after Benda, it's been at least a year, and their T cells have had time to recover. It's one less thing to worry about if you've had Bendamustine.

Next on the list is number 2, which isn't directly about Follicular Lymphoma, but it's really interesting to me. It's "2267 Toxicity Outcomes in Phase 1 Lymphoma Trials: Variable Reporting with High Use of Minimizing Language in Published Abstracts at International Conferences." I'm especially interested in this because I have a real interest in the language we use to talk about cancer, but also because this research affects the way I write the blog. The researchers looked at presentations from major cancer conferences (like ASH) that reported results from phase 1 clinical trials. They were interested in how safety was discussed in these presentations. There's kind of a tension here. On the one hand, phase 1 trials are all about safety; the whole idea is to figure out what dose of a new treatment will work well but do the least harm. On the other hand, someone presenting data about a new treatment wants to make it sound as good as they can, so there's a temptation to be more positive than they should be. As the research points out, you'll se a lot of language like "tolerable" or "safe" or "manageable" when talking about side effects, but there's no accepted definition for what those words mean. So it's important to look carefully at the numbers and not just rely on the language being used.

(This hits home for me, as someone who writes about clinical trials all the time. I have to force myself sometimes to bring up the potential safety issues. Just a couple of days ago, my wife was reading my last post, in which I mention that several patients died during the study. She really doesn't like to read about that. I pointed out that, first, a number of those patients died because the study happened during the Covid pandemic and had weak immune systems, something I didn't mention in the blog post, and second, it's important information and needs to be mentioned. I remember a few years ago someone talked about me on a Facebook group, and someone else said I could be too negative sometimes in my writing. It's true, I can be negative but I try hard to be just the right amount of negative, not too negative. I don't see much point in not giving you the potential bad with the good. False hope isn't good for anyone. Every treatment comes with some trade off,and we need to remember that.)

Number 1 on the Leonard List is about Follicular Lymphoma: "1652 Outcomes in Early Relapse of Follicular Lymphoma Versus Early Histologic Transformation Following Firstline Immunochemotherapy in Follicular Lymphoma." In this presentation, the researchers look at the two situations that are most troubling for FL patients: transformation and POD24. First, POD24 stands for "Progressio of Disease within 24 months." FL patients with POD24 are those who have received immunochemotherapy (like R-CHOP or R-Benda) and then have their disease get worse with the next 24 months. About 20% of FL patients will fall into this category. Transformation happens when our nice slow-growing cancer turns into a different type of lymphoma, one that is fast-growing. Both POD24 and Transformation lead to a lower Overall Survival rate. The researchers here show some evidence that there is overlap in these two groups. That is, many patients with POD24 also have transformed disease. But in looking at the bigger picture, they are being counted twice. In other words, look at 10 FL patients and see that 2 have POD24 and 2 have Transformed disease, but really it's one of each, plus one with both -- 3 patients instead of 4. That matters when statistics are put together about POD24 -- maybe the Overall Survival numbers are better of patients with Transformed disease are separated out from those POD24 patients who have not transformed. Dr. Leonard wants to see the details of the research next week, but thinks this could put even more emphasis on Transformed disease. POD24 is really a label that needs to be separated into at least two groups. It will be interesting to see what the Lymphoma experts have to say about this presentation later on. It's a big deal if it ended up #1 on the Leonard List.

Dr. Leonard also gives 5 bonus presentations on the podcast, and FL makes an appearance here, too. It's one that I have already written about a few days in the blog-- "782 Travel Burden and Travel Costs of Bispecific Antibodies in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma and Relapsed/Refractory Follicular Lymphoma. I am pleased that Dr. Leonard chose a study that looks at Quality of Life and the time and money that comes with treatment, even apart from the cost of the treatment itself. As Dr. Leonard says, "My takeaway is just that this is a factor that is interesting and important to our patients and something we don't take into account and probably we should be thinking about a little bit more. Taking 50 or 80 hours or longer out of work or other things you have to do if you're a family member or a patient, and the cost of $2,000 and $3,000 in some cases for patients to travel, this is a burden of care that we don't always think about in our practice and probably should be paying some attention to."

Excellent analysis, Dr. Leonard.

So there's the Leonard List for 2024. Follicular Lymphoma played a pretty big role this year, bigger than most years. I'm pleased I was able to describe a few important studies all at one time for you. 

I'll try to get one more preview in before the meeting starts at the end of the week. Once that happens, the previews are over and the reviews begin. I'll report on what the cancer news websites are excited about, and what the experts have to say in the days and weeks after the meeting.

Stay tuned for more.

ASH Preview: A "Triumph" for Tafasitamab

OK, this next ASH preview is an interesting one, not just because of the content of the presentation, but also the situation surrounding it. 

The presentation is called "LBA-1 Tafasitamab Plus Lenalidomide and Rituximab for Relapsed or Refractory Follicular Lymphoma: Results from a Phase 3 Study (inMIND)." The "LBA-1" means "Late Breaking Abstract," one that was added very recently, so it's not part of the regular numbering system.  

The abstract describes a very successful phase 3 clinical trial in which Tafasitamab, a monoclonal antibody, was added to the already well-known combination known as R-squared (Revlimid and Rituxan). An article on the Fierce Pharma web site says it "triumphs," which is why I used that word in my title for this post. It will likely go to the FDA for approval as a treatment for relapsed/refractory Follicular Lymphoma.

Before I get into the specifics of the trial, I want to explain why I think the situation is so interesting.

It's partly because I had no idea this was coming. I'm not an expert, as I have said many times before. I'm not an oncologist or a cancer biology researcher. I'm a Cancer Nerd, someone who was diagnosed with FL in 2008, and who reads and writes a whole lot about FL. I'm not an expert, but I consider myself pretty well informed when it comes to Follicular Lymphoma.

And yet, when I saw this headline on Fierce Pharma, I had no idea what Tafasitamab was, or that it was close to finishing a phase 3 trial.

The other reason it's so interesting is that I immediately searched this blog to see if I had written about it before and had just forgotten about it. And I found one post from the past that I had written. This how that post, written April 22, 2021, started out:

I like surprises.And I have to admit, this one surprised me. As much as I follow what's happening in the world of Follicular Lymphoma, I think this is the first I've heard of Tafasitamab. I searched the blog, and couldn't find any mention of it anywhere. But a phase 3 trial is just starting, looking at Tafasitamab combined with Lenalidomide (Revlimid)  and Rituxan (the two treatments that make up R-Squared). The trial involves patients with Relapsed and Refractory Follicular Lymphoma (they've already had at least one treatment that didn't work or stopped working).

 I laughed out loud when I read that. Apparently, I have heard about this treatment twice -- once at the start of the phase 3 clinical trial, and now at the end of the trial. 

This probably says more about the treatment and its maker than it does about me. Tafasitamab is also known as Monjuvi, and it was approved for use on DLBCL by the FDA in 2020 and by the EU in 2021. So it had already gone through all of the really heavy marketing and advertising that would have put it in the news. By the time I read about it, and especially since it was in a trial as part of a combination, it wasn't so "in your face" as it probably was its first time around.

So on to that "triumph" of a trial.

Tafasitamab is a monoclonal antibody, like Rituxan. But it's different in a couple of ways. First, it is "humanized," meaning it was developed from human cells, not mouse cells, like Rituxan. That has the potential to make it more effective and safer )fewer allergic reactions). The second difference is that is targets CD19, a protein on the FL cell. Rituxan targets CD20. So you have two different ways for an antibody to get to the cell. 

Tafasitamab has already been approved in combination with Revlemid (also known as Lenolidamide) for DLBCL. So you had the potential for a really great combination -- everything works together, compliments each other, and should have few new serious side effects,

And that's pretty much what the Tafasitamab + Rituxan + Revlimid combination does. The trial involved 548 patients with r/r FL. Half were given R-squared, and the other half had R-squared plus the Tafasitamab. 

The results were great. The patients in the TRR group had a median Progression Free Survival (their disease did not get worse) of 22.4 months, versus 13.9 months in the RR group. And that increased PFS was true no matter what group they looked at  -- POD24 patients, those who had received Rituxan, rhose who had recieved multiple treatments. The Complete Response Rate for the TRR group was 49.4%, versus 39.8% for the RR group. The Overall Response Rate was 83.5% versus 72.4%. 

As for safety, the results were similar for both groups. 99% of patients had some side effects in both groups (not a surprise). Grade 3 or 4 side effects happened in 71% of patients in the TRR group versus 69.5% of RR, and serious side effects were 36% versus 32%. During the study, 15 patients in the TRR group died, 5 because of disease progression and 6 because of side effects, versus 23 in the RR group (17 due to disease progression and 6 from side effects). Those death statistics are a good reminder that no treatment is without side effects, often very serious side effects.

But the bigger picture is this: adding Tafasitamab to R-Squared makes a very good treatment even more effective, and without a great increase in safety issues. 

I'm guessing this is going to be the Big Story about Follicular Lymphoma when the ASH conference is over, and we'll be hearing more excitement about it from the experts who give their opinions about things. The conclusion to the presentation abstract says this combination "represents a potential new standard of care option for patients with R/R FL." In other words, this will be the one everyone defaults to. That's a big claim. We'll see how the FDA process goes. But it will be really interesting to see what the experts have to say. Those are some very good numbers.

More to come, about this treatment and others.

ASH Preview: Travel Costs for Treatment

The Follicular Lymphoma Foundation has left their survey open for a few more days. Click here to fill it out, and be sure to ask your caregivers, spouses, and partners to fill it out as well. 

I bring this up for two reasons. First, because I want people to take the survey (especially caregivers, whose voices aren't usually heard). But second, because one of the features of the survey involves how long you'd be willing to travel to receive a treatment. It's a really interesting question that doesn't get asked much. For someone like me, with a medical school,and cancer center pretty close by, this isn't a big deal. But for lots of folks, travel to a cancer center can take a very long time, especially for a newer or more complicated treatment that can't be done in a doctor's office treatment room (something like CAR-T comes to mind).

So I'm highlighting an ASH presentation that looks at this problem: "782 Travel Burden and Travel Costs of Bispecific Antibodies in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma and Relapsed/Refractory Follicular Lymphoma."It's one of those Quality of Life research projects that needs more attention.

The research looks at patients with both DLBCL and Follicular Lymphoma, but I'm going to focus on the FL patients. (The difference between them is in how often they are given this particular treatment.)

Specifically, the research looks at Bispecifics -- Mosunetuzumab and Epcoritamab, which have been aproved for FL. These are among the "newer or more complicated" treatments that aren't available in every treatment room, so some patients with FL need to travel to get to them. Travel costs money, but it also costs time -- time in the car, in the treatment room, and away from a job. 

The researchers looked at 114 patients with FL and DLBCL over a year. They looked at the distance that the patients had to travel to get to their treatment, and how much time it took. Then they calculated the financial cost by applying U.S. government standard mileage rates (the amount per mile that people can be reimbursed for in some jobs) and how much money they lost from missing work (using average wages).

Because Mosunetuzumab and Epcoritamab require different schedules, they figured out how many doses each would require over a year, and calculated them separately.

So what did they find?

The overall average one-way distance traveled was 80.1 miles, and took 84.5 minutes. About 56% of the patients traveled less than 30 miles and 24% traveled more than 60 miles.  

When they added things up, the FL patients who had Epcoritamab traveled 4486 miles over 70 hours, costing the, $5758. The patients who had Mosunetuzumab traveled 3,044 miles for 54 hours, costing them $3907. That's significant.

I don't think the researchers are saying Mosunetuzumab is better than Epcoritamab because of the costs associated with travel. That's a very individual thing -- for someone like me, close to a cancer center, where I could receive either one, the costs probably don't matter all that much. The larger point is to make oncologists aware of these costs -- in money and time -- and to make sure they are a part of the conversation that they have with patients about treatment. It's easy to look at an article in a medical journal and say "My patients have a choice of treatment, and X looks like it is 5% more effective that Y, so that's what I will recommend." That 5% difference might not mean much if there's a 2 hour drive involved every week.

(And that, of course, is exactly what the FLF survey is getting at -- trying to get enough data to show oncologists that these things matter to patients, and that Quality of Life should be a part of any treatment decisions that they make.)

It complicates things for everyone when you start bringing in more factors to consider at treatment time. But it's so important to get that bigger picture. 

I'll keep looking for interesting Quality of Life research in the ASH abstracts, along with interesting research on treatments. Look for more soon. 

 

ASH Preview: Statistics on Watching and Waiting

 As I said in my last post, there are a lot of interesting presentations about Follicular Lymphoma  coming up at ASH, and I hope to cover a lot of them. And as I said, I want to start off with a presentation about Watching and Waiting.

If you've been reading for a while, you probably know that I was diagnosed with stage 3, grade 1/2 FL in January 2008. My disease was slow-growing enough that I was able to watch and wait for exactly two years -- I started Rituxan on my second diagnosiversary. The treatment began because of swelling in my leg, probably caused by nodes that were pushing up against something. 

Watching and waiting made absolutely no sense to me when I was diagnosed. Why would anyone choose to not get treatment? But I learned that watching and waiting made sense for some FL patients whose disease was slow-growing, because it essentially delayed using up a treatment. Back then, there were fewer treatments available, and it was assumed that the disease would come back and need another new treatment. The hope was there would be enough treatments, and enough time between them, to outlast the disease.

For a while, there was lots of research on W & W, trying to find some negatives about it. But there was never really anything discovered that upset what the previous research showed -- that there was no real difference in Overall Survival between patients who were treated right away and those who waited. I remember a researcher arguing that W & W was unnecessary because we had more treatments available, and something like Rituxan could be used a s first-line treatment because it was less aggressive than other options. That got debated for a while and then people stopped talking about that.

[I've been writing this blog for almost 17 years, so I don't remember a lot of details, but if you want to be a Cancer Nerd and search the blog for everything I've written about watching and waiting, you have that option.]

So let's take a look at this ASH presentation -- "4416 Practices and Outcomes during a Watch and Wait Approach for Follicular Lymphoma: A Study from the Australasian Lymphoma Alliance."It looks at 267 patients from Australia who were diagnosed with FL and then watched and waited.

It doesn't necessarily present anything new, but it gives an interesting snapshot about what happens when patients watch and wait. Given that I've had a couple of conversations recently about this, I'm guessing there are a bunch of you who are curious about this. Here are the bits that I found most interesting:

• For the patients in the study, the median Time to Treatment was 4.88 years (meaning half of them waited for over 5 years). About 30% of the patients were able to continue to watch and wait for 10 years. That's a long time. (I'm thinking of reader Chip, who was getting a little antsy after 3 years. It can go on for a while, obviously.
• While they were waiting, they had a median of 8 appointments with their oncologists and 2 CT or PET scans.This is pretty interesting, too. I know when I was first diagnosed, and we agreed to watching and waiting, I expected to see the doctor very frequently, and at first I did. But then we stretched out the every 3 months. In this study, if patients waited for 5 years and had 8 appointments, then they were seeing their doctor every 7.5 months. If you're newly diagnosed, keep that in mind -- patients don't need to be seen very frequently, if that's something you're concerned about. The reason is related to the second bit of information here -- only 2 scans in 5 years. Again, I thought I would get scanned every few months. But we shouldn't be exposed to that much radiation -- a scan every year is probably the most frequent you'd need, and even that is a lot of scans. I remember reading a study that said that most patients notice symptoms themselves and then alert their doctor about it.  The new symptoms (like my swollen leg) aren't found in scans or during a doctor's visit. They are found by patients. Why? Because we know our bodies and we know when something isn't right. Trust yourself. 
•  Just to be clear -- the range of doctor appointments in the study was 1 to 34, and the range of scans was 0 to 14. Don't take the median to be the goal. If your doc wants to meet or scan more or less than that, then ask why and if you're ok with the answer, then meet more or less frequently. But it's OK to ask to meet more frequently, if only for the peace of mind (I meet my doctor way more frequently than I need to, even 16+ years later, because it gives me a little comfort.)
• Complications, including patients having new symptoms, happened to 28% of the patients in the study. About 13% of them had transformed disease, where their slow-growing FL turned into a more aggressive type of lymphoma. About 12% had pain or discomfort,  3% had hydronephrosis (swollen kidneys) and 2% had thrombosis (blood clots). Most, it seems, it not have serious medical complications.
  
•  Here's a big one: There was no mortality associated with a WW approach. No one died because they watched and waited. That's worth mentioning. I know I had the fear that I or the doctor would miss something important. That doesn't happen.
• Back to scans. For those who did get scans, about 20% were for "surveillance," basically to take a look around and see what's going on. The other 80% were triggered by "clinical findings," either discovered or confirmed by a doctor;s examination.
  
• During the 5.5 years of follow up, 138 of the 267 patients started treatment -- just over half. For those who did start treatment, 38% did so because of tumors getting larger, 25% transformed, 17% had organ compromise, 7% was for potential organ compromise (I think this was technically the reason I started treatment), 7% had cytopenia (low blood counts). So for those of you who wonder when to start treatment, there are lots of reasons, and I think it's safe to say that you'll know when something is up.
  
•  This is important too: 1 of the 138 patients who started treatment did so by choice. That is, there weren't any symptoms or complications that made the doctor say "It's time to start." The patient said, "I can't do this anymore. I need to start treatment." And that's OK.  Honestly, I'm surprised it was only one. As I have said many times before, we have a disease that has emotional symptoms as much as it has physical symptoms, and for those who are watching and waiting, there are more emotional than physical symptoms. If a treatment results in too great of a physical toll, we stop doing it. If the choice to watch and wait takes too much of an emotional toll, then ask to stop. that's a legitimate choice.
• And finally, it's the same story as I heard 16+ years ago -- Overall survival was similar for watching and waiting than it was for patients being treated. 

So there you have it -- as up-to-date a picture of watching and waiting as we have. If you're watching and waiting now, and you have questions, I hope this answers them. It's such a strange situation to be in, it's only natural to have questions. At least for now, I hope you have something to compare to, and you can see that watching and waiting can be a good choice -- one that won't results in any special problems, as long as you pay attention to your body and let your doctor know when something is off.

There's another interesting watching and waiting presentation that I may write about. But maybe not  -- this one answers lots of questions, and there is so much more to share with you.

Come back soon.

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

One final push for patients and caregivers to take that FLF survey. It closes on November 19, so do it soon if you haven't yet!

ASH Abstracts Are Here!

Before I get the Cancer Nerd stuff, I want to remind you about the Follicular Lymphoma Foundation survey that I linked to in my last post. 

The survey is about how patients with FL make decisions about treatment. It should take about 10 minutes to complete, and will provide valuable information that hopefully will be presented at a medical conference next year, where it can be seen by oncologists and researchers and those who manufacture the treatments. 

This link will take you directly to the survey.

UPDATE: The FLF is getting a good response from this survey from patients, but they'd love to hear fro more caregivers -- a spouse or partner or family member or friend who helps you as a patient. If you're a patient, could you please share the link with your caregiver and ask them to take it? Caregivers don't get enough credit for how important they are in the decision-making process. This is a great opportunity for their voice to be heard.

 Thanks for considering it.

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

Now, back to that Cancer Nerd stuff.

The abstracts for the ASH meeting are now available!

ASH is the American Society of Hematology, and their annual meeting is the largest gathering of blood cancer specialists in the United States. It takes place in early December every year. This year is it December 7-10.

Much of the meeting involves presentations of research on blood cancers and other blood-related diseases. (It's in San Diego, California, so I assume some of the meeting involves brightly-colored drinks with little umbrellas in them, too.)  About a month before the meeting, ASH published the abstracts -- summaries of what the presentations will be about, so those in attendance can plan out which sessions they want to go to. 

Every year, I like to go through the abstracts related to Follicular Lymphoma and preview some of the more interesting ones. My quick search says there are 329 abstracts for Follicular Lymphoma. You can see them yourself here.  

Some years, there isn't much that's very interesting. But this year, even a quick look at the titles is getting me excited. 

First, though, a few things that I am not seeing in my quick look at the abstracts.

First, I'm not seeing any game-changers. Some years there's a presentation that is so important that they move it to a very big room so they can fit all of the people who want to hear about it. (The last one of those for FL was when they discussed the results of the R-squared trial.) I don't see any of those this year. And that's OK.

I'm also not seeing too many new treatments. There are a few, but not as many as some years. These re usually reports of phase 1 and 2 clinical trials, which means they are very early in their process. They're always exciting, but don't always play out as one would hope, and they aren't heard from again. I do see a few, though, and I'll try to highlight the exciting ones.

What I am seeing is a lot of research on treatments that have already been approved. Some are "real world" studies, looking at a treatment outside of a clinical trial, so there are fewer restrictions on who can actually receive the treatment. Some are combination studies, looking at treatments that have been approved on their own to see how they work together. Some are long-term follow-ups to approved treatments.

Those kinds of presentations are really interesting, too, because they teach us more about the treatment and how effective it is for certain patients. They can be less exciting than a presentation for a treatment that hasn't been approved yet, and that comes with the promise of big change. But those less-exciting presentations often give us incremental change. No big leaps forward, but they do move us forward. And that's a great thing, too.

I'm also seeing some presentations about Quality of Life issues. That's excellent -- researchers are paying attention to it, and oncologists will be hearing about it. There's more to treatment than just how effective it is. There's everything that happens when we live our lives outside of the treatment room. That matters a lot.

I see a couple of presentations about watching and waiting that I'm excited about (and might start off with, since I'm always interested in it).

Finally, there's an "Education Program" about FL that;s in a big room. It's not presenting anything new, just educating oncologists about what the latest is for Follicular Lymphoma. There's one presentation during the session called "Follicular Lymphoma: In Pursuit of a Functional Cure."  The description of the presentation, from Dr. Judith Trotman, and Australian oncologist, says "In this talk, Dr. Trotman will provide the survival data to equip clinicians in framing optimistic initial conversations with most patients at diagnosis of advanced stage FL. She outlines the expectations of longevity and a"functional cure" for many." A functional cure is the idea that many of us will get a treatment that lasts so long that we don't need another, even if we still have some evidence of the disease still hanging around and remaining stable.

That one looks great, and I hope I can get access to a recording of it after it is over. Unfortunately, ASH doesn't provide special registration rates for independent cancer advocates the way ASCO does, so I'd have to pay for access. Maybe I'll get lucky and they'll post the video for free someplace.

So look for some interesting ASH previews in the next few weeks. Always a special time.

(And don't forget that FLF survey! Caregivers, too!)

More to come very soon.

 

Please Take This Survey about Follicular Lymphoma

Hello all.

I'm finally putting up that post that I promised last time. 

I'm linking to a survey here, and I'm asking you to please consider taking it. The link comes directly from the Follicular Lymphoma Foundation, so it is safe.

https://hab.medefield.com/wix/01234/p979123129511.aspx

The FLF developed this survey (I helped a little bit!) to better understand how patients with Follicular Lymphoma make decisions about treatments. It can also be taken by caregivers and physicians to get their input as well. (The survey will direct you to a different version after it asks you if you are a patient, a caregiver, or a physician.)

The survey is open to residents of the United States, United Kingdom, Canada, Australia, and Spain. You can see the survey in English or Spanish. The announcement for the survey is available on the FLF website if you'd like to read a little more about it.

The survey should take about 10 minutes to finish (maybe 15 minutes if you read slowly and carefully like I do). It is completely anonymous.

The survey will first ask you some basic information, and then it will describe the survey methods for a few screens to make sure you fully understand what you need to do. I don't want to give too much detail here, but it will basically ask you to choose between two hypothetical treatments (they aren't real, or even in development). They will distinguish between the two treatments by showing how type are different, in terms of how long you are likely to be in remission, what kinds of side effects are common, and how it is administered. You'll choose the treatment that you would prefer. You'll do that 11 times. 

It's not hard at all, once you read through the descriptions of how it all works. 

The FLF plans to present this information at a future medical conference. They hope the information will be seen by researchers and influence how they develop new treatments. (For example, if the survey showed that patients with FL would overwhelming prefer one way of administering treatments, then maybe researchers will be sure to develop treatments that can be administered that way.)

So this is your way to potentially have a hand in how research gets done in the future. Very cool. 

 

Thanks for taking the survey. It helps all of us.

 

National Workshop: Lymphoma Research Foundation

Well, I have a post that's all written, that I had planned to put up this weekend, but I need to hold off on showing it to you. I'll explain later.

For now, here's a reminder that the Lymphoma Research Foundation is holding its virtual National Lymphoma Workshop on November 16. This is a day-long event, completely online, and it's all about the latest research in Lymphoma ("Understanding Lymphoma Basics and Current Treatment Options").

The workshop is chaired by Dr. Neha Mehta-Shah of Washington University in St. Louis, Dr. Craig Portell of the University of Virginia, and Dr. Carrie Thompson of the Mayo Clinic. I'm not as familiar with the work that Drs. Mehta-Sha and Portell do, but I've written before about Dr. Thompson, who does  a lot of research on Surviorship and Quality of Life. I think she's great. I'm sure the other two will be equally good. 

I attended one of these in the past, and it was excellent. You can expect to hear information that it meant for patients who are newly diagnosed,  those who are relapsed/refractory, and information about survivorship. There will also be a session devoted to Follicular Lymphoma, where they may talk about treatment options, clinical trials, and new therapies. And there will be a chance to submit questions for the experts to answer.

Registration is required. You can find out more details and get the registration link here.

I'll have more for you soon. This is about my busiest time of the year for me, with lots of work stuff, plus some really interesting cancer-related advocacy work that I'm doing. I'll try to share more about it when I can stop and take a breath.

Stay well.

Watching and Waiting and Wondering

There was a comment on a post from earlier this month from an anonymous reader that made a good point -- lots of what we read is based on what has happened to a group of people, but there is a lot of variation within that group. So much of what happens to patients with cancer is very personal, in the sense that each of our situations is very different from other patients'. I think that's especially true of patients with Follicular Lymphoma, since our disease is so variable. People with the same diagnosis (grade 2, stage 4, whatever) can have incredibly different experiences. It's good to remember that.

The anonymous reader who left the comment followed up with an email, and we had a very nice exchange over a couple of days. (I'm always happy to get emails and comments  from readers.) His name is Joel and he's fairly recently diagnosed. He shared his story, and some of the details were very familiar. Joel was diagnosed at 40 (same as me). Grade 1, Stage 3 (me too!). Very active and healthy (I was running 5k and 10k races at the time). Diagnosis was kind of accidental (I was getting over pneumonia and a large node showed up on a chest scan, and then another node popped up near my hip). Very similar stories!

I hope the similarities continue. I feel like I've had a very lucky path as a patient with FL. The disease has remained fairly slow-growing for me and hasn't caused me too many problems. I know that's  not true for everyone.

One of the other things we talked about was making treatment decisions, especially for that first treatment. As you might know, if you've been reading for a while, my FL was slow-growing enough at first that I was able to watch and wait for two full years before I needed treatment. And then I had six rounds of Rituxan. I haven't needed treatment since then -- almost 15 years. 

Like I said, I know how lucky I am.

At about the same time we were having this exchange, I got an alert about a new article from WebMD called "Follicular Lymphoma: Why “Watch and Wait” May Be the Best Approach." A better title might have added "for some patients." It's obviously not true for all patients with FL, which the full article makes clear. And that's the point of all of this -- we all have different situations, even of they seem similar on the surface.

I made a video a few years ago that introduced a WebMD slide show on what patients should do their own careful research. It is, sadly, no longer online. WebMD can kind of a mixed bag. They can be incomplete and alarmist sometimes, and really useful at other times. I think this article on watching and waiting is actually pretty good. It explains the idea well, and gives what I think is solid advice on whether or not it is appropriate, and when it is time to switch from waiting to treating. I remember seeing an article on watching and waiting right after I was diagnosed, when I was first doing internet research and trying to figure out what FL was. I remember seeing the article and thinking "Who the heck would get a cancer diagnosis and not have treatment?" A month later, that was me. It says something about how poorly that article was written. I think the WebMD article would give good advice to someone who was trying to make that decision. 

It's rare that someone who has just been diagnosed has a clear enough head to be able to do that kind of research and make an informed decision. (Joel is a full-on Cancer Nerd, based on our exchange. I can confirm.) Much easier to see clearly when the initial shock of a diagnosis has work off. That's one advantage of being diagnosed with a slow-growing cancer like FL -- for many of us, we have some time to learn and then make decisions. 

And after we've had active treatment, we hopefully have time to continue learning and being prepared for any future decisions (if that's how we choose to deal with it -- pushing it out of our heads completely is also an acceptable choice).

All of this has been going through my head for the last few days, since Joel first wrote. Getting a new diagnosis is so hard. I am grateful that I found an online support group for NHL with some people who were willing to share their stories and give some information. I grew pretty close to some of them, and I still keep up with their lives. It's so important to share what we know. And it doesn't have to be all Cancer Nerd-y stuff, either. Just our living through what we have lived through is worthy of sharing, and incredibly valuable to other patients. If nothing else, it gives them hope. They know there's a tomorrow. Sometimes that doesn't seem like a sure thing, especially when you've just been diagnosed.

So I hope Joel, and any other folks who were recently diagnosed, are doing well and finding the knowledge and support and comfort that you need. 

Take care, everyone.

Pembrolizumab (Keytruda) for Follicular Lymphoma

The medical journal eJHaem just published an article called "A Phase 2 Study of Frontline Pembrolizumab in Follicular Lymphoma." It's very interesting to me for several reasons, most importantly because it reports the results of a clinical trial for Follicular Lymphoma. But there are others, too, which i will get to.

Pembrolizumab is also known as Keytruda, and it is a very important treatment in cancer. It is a PD-1 inhibitor, meaning it stops the effects of PD-1, or Programmed Death 1. It's a very cool immunotherapy treatment. PD-1 is a protein that is an important part of the immune system, because it keeps immune cells from doing their job too well. If an infection occurs, PD-1 keeps the immune system from attacking too many cells, which would result in an autoimmune issue, where the immune system attacks healthy cells. It send s a"programmed death" signal to some immune cells, basically telling them to stop working. 

In terms of cancer, PD-1 works on immune cells that could be going after cancer cells. So a PD-1 inhibitor stops the PD-1 from stopping the immune cells. In other words, it allows the immune system to work on the cancer cells. 

What makes Pembrolizumab so important is that it works on lots of different cancer cells. We usually think of cancer in terms of body parts -- breast cancer, colon cancer, blood cancer. When we think that way, it makes us think of the cancers as all being very different. A traditional chemotherapy that works on breast cancer probably won't work on lung or brain cancer. 

But the discovery of PD-1 changed all of that. PD-1 is present in the cells of lots of different body parts. So Pembrolizumab has been approved for use in patients with lots of different types of cancer -- melanoma, several lung cancers, classical Hodgkin's Lymphoma, urothelial carcinoma, head and neck cancer, and renal cell cancer. Former U.S. President Jimmy Carter received Pembrolizumab; he might be its most famous user.It's been a real game-changer for many patients with many types of cancer.

But not Follicular Lymphoma. 

I've written about Pembrolizumab and FL a few times. The first time was in 2016. I looked at a couple of pieces that Dr. John Leonard had written about new treatments for FL, and he mentioned a phase 2 study of Pembrolizumab and Rituxan. In the other times I've mentioned it, it was usually to say that results from a study weren't as strong as researchers had hoped. 

And that's the case with this one, too. It look at a phase 2 study of just Pembrolizumab indolent B cell lymphoma, including FL. In this fairly small study, 9 patients with Follicualr Lymphoma were enrolled. The Pembrolizumab wasn't very effective -- 3 of the patients had a partial response, 3 had stable disease, and the other 3 had their FL get worse. Safety wasn't much better than effectiveness. Two of the patients had grade 3 (serious) side effects. Both had transaminitis (high levels of liver enzymes and the blood) and one of them also had hypophysitis (an inflamed pituitary gland).

All of that was enough for the researchers to say "Frontline pembrolizumab for FL is associated with limited responses and a clinically significant rate of IRAEs. Alternative strategies for targeting the TME [Tumor Microenvironment] in FL should be explored." in other words, this one isn't working.

It certainly makes sense to give Pembrolizumab a try in FL. Why not? It works in lots of other cancers, even in another blood cancer (Hodgkin's Lymphoma). But for whatever reason, inhibiting PD-1, at least with this treatment, just doesn't do the job. 

As I said, the results are most interesting to me, but there are some other things about the article that are also interesting.

First, I love the title -- "A Phase 2 Study of Frontline Pembrolizumab in Follicular Lymphoma." If this had been a successful trial, the results would have been given to us upfront, something like "Pembrolizumab Induces Durable Response in Follicular Lymphoma: Results of a Phase 2 Study."I learned that lesson long ago. When you're writing an email with good news, put the good news in the subject line. If it's bad news, make the subject line neutral and bury the bad news in the middle of a paragraph halfway through the email. It's fascinating that the same strategy turns up here.

But even more fascinating is that the bad news turns up at all. It is very rare to see a negative study get published. I could find dozens of examples in this blog over 16 years of reports of phase 1 and phase 2 studies that were very enthusiastic, but were never heard from again. The later studies weren't successful, the researchers never reported the results. I would love to see more negative studies published. They can be just as helpful as the successful ones.

But those studies were also probably commercial, and if a business has sent millions of dollars trying to develop a treatment, they really have no incentive to advertise to the world that the treatment didn't work out. More likely, the company died and the people working for it moved on to something else.

What makes this study different is that Pembrolizumab was already a successful treatment, already making billions for its makers. The authors aren't business people; they are academics and researchers, doing a study with a treatment that has already been approved. They really do have some incentive to share what they learned, even if the treatment wasn't successful. The study was successful -- we learned something from it.

So I'm enjoying this "failure," because it is so rare to read one. I don't think we've seen the last of Pembrolizumab for Follicular Lymphoma. There are still some studies out there. Maybe one of them has just the right combination or the right dosage to make it work. It would be great to add FL to that long list of cancers that Pembrolizumab can treat successfully.

But in the meantime, as the authors of the article say, it's time to try something new and stay hopeful.

FLF Patient Survey Results

The Follicular Lymphoma Foundation published the results of its recent survey of Follicular Lymphoma patients. The survey focused on immunotherapy and communication preferences. There are some really interesting results, even for someone like me who spends a lot of time thinking about FL.

The FLF, for those who don't know, is an organization with a global mission. They provide information and support for FL patients, including funding some important research. If you haven't been to their website, it's worth a visit.

Their global mission is reflected in the survey. They include results from 791 FL patients from 49 different countries. 

One question that they asked was which treatments the patients had received. Almost 60% had received some kind of chemotherapy. 18.2% had Rituxan or Obinutuzumab on their own. 6.2% had R-squared. And 19.5% had received some other treatment. That's always interesting to me, as someone who reads (and writes) about new treatments a lot. It's easy to think that traditional chemo must be on its way out. But even with newer possibilities, chemo remains not just one options, but the option for many patients. And of course, it's a very effective option for many patients.

Along those same lines, only 1.6% have received CAR-T and 2.9% have received bispecific antibodies. Those are very small percentages, given how much excitement there is around them.

Part of the issue is they are approved for a very small percentage of patients. And then there is the cost associated with something like CAR-T.

But this is all a very good reminder for myself that what I write about is often the future, and not the present. All of the excitement, all of the clinical trials, all of the research -- that might be the reality for us in the future. But right now, patients are much more likely to get chemo, or Rituxan, or even R-squared. They are the "standard of care." It's definitely worth understanding what kinds of treatments are out there, because not every oncologist will go to the newer stuff.

Along those lines, another interesting result from the survey -- respondents were asked to rate their awareness of immunotherapy from 1 to 5. The average was 2.16. The FLF says this result was pretty consistent no matter what country they came from. That's very low. There's a critical need for information among FL patients.

When asked which types of sources they found most helpful, or would like to see more of, the respondents said Educational videos featuring healthcare professionals were most helpful. (The FLF has a bunch of these on their website.) Next came testimonials or surveys from other patients, then scientific articles, and then Frequently Asked Questions from other patients. None of these really surprise me, and it's good to see that healthcare professionals are most helpful. Patient stories are great, and I love reading them. But I've also seen lots of less-than-helpful information from other patients. It's good to see FL patients are valuing good information.

That said, the FLF would also love to hear patient stories as well. If you're interested in sharing yours, read more here about how to do it. 

There are lots of other interesting results from the survey, but I want to highlight one more. Just 9% of FL patients in the survey said they have participated in a clinical trial. They seemed really low to me. So I looked at an article from the Journal of Clinical Oncology from earlier in this year that looked at how many cancer patients in the United States have participated in a clinical trial. 

That article said that just 7% of cancer patients in the U.S. have participated in a clinical trial for a treatment. So the FL population seems more or less in line with that. But that article pointed out that clinical trials are only one kind of research that cancer patients can participate in. Almost 13% have been involved in biorepository research (where a tissue sample is saved for later examination), 7.3% in registry research (where their medical records are used for studies), 3.6% in genetic research, 2.8% in Quality of Life research, and  2.4% in economic research. So while we should all at least consider clinical trials for treatments when appropriate, we should also remember that there are lots of other ways to help with research.

So the Follicular Lymphoma Foundation survey is pretty interesting, and I encourage you to read the article that discusses the results. And while you're there, take a look around the rest of their website. Lots of god stuff there,

Humor and Cancer

About a month ago, I came across an article in the Journal of Clinical Oncology that I thought was interesting, and I forgot about it until this morning. It's from a special section of the journal called "The Art of Oncology," where they publish personal stories from doctors and other healthcare professionals (and occasionally patients). The rest of the journal mostly deals with the science of oncology, with heavy research. But the art of oncology is about other things, mostly dealing with people. That part is a lot messier than the science.

The article I looked at was called "Just Humor Me," and it's by an oncologist who argues that the cancer clinic is an appropriate place for laughter. (If you are sometimes hesitant to read the things I link to because they can be hard to read, then try this one. Very readable.)

I would certainly agree that the cancer clinic is a place for laughter. But I think pretty much every place is a place for laughter. I'm not the only one. The author shares some research: "One survey of patients undergoing radiotherapy in Ottawa found that a stunning 86% of patients felt that laughter was somewhat or very important to their care, whereas 79% felt that humor decreased their level of anxiety about their diagnosis. If we had a drug that decreased anxiety levels in 79% of patients, had minimal to no side effects when used correctly, and cost the health care system zero dollars, should not we be using it?"

That's a very good point.

I used to write a lot more about cancer humor (search for "cancer humor" in this blog and you'll see some of those early posts). I think I do less of it now because humor is still important to me, but it's maybe less vital to my health. When I was first diagnosed, humor was definitely a coping mechanism, which is common for many patients (or Follicular Lymphoma or any other disease or condition). There was definitely a sense for me of "not letting cancer win" by taking away something I love -- laughter. 

I remember, a few days after getting diagnosed, my parents came to visit, so they could see how we were doing and try to gauge how out young kids were doing. My parents were in the other room playing with their grandchildren, so I finished making dinner and set the table. My mom heard me banging around the kitchen, and came to see if she could help. Too late; I had already gotten everything ready. So I said, "I did it all. Nice. Make the guy with effing cancer do all the work." She laughed, which was what I expected. Then she hugged me and said, "WE shouldn't be laughing at this." To which I said, "We can't ever stop laughing at this."

A few years later, after she was diagnosed with ovarian cancer, we all went to a baseball game. She and got in line to get ice cream for everyone. As we got to the front of the line, I whispered to her, "You should tell the ice cream guy you have cancer. Maybe he'll give it to you for free." She laughed. "I can't do that." But after she ordered, she said very quietly, "I have cancer." The young man didn't hear her, or didn't know what to say, and as we walked away, Mom said, "I didn't even get free sprinkles." It made me laugh. 

I laugh, too, at the absurdity of it all. I went to the dermatologist a couple of weeks ago to follow up on my skin cancer surgery from about a year ago, and as I got undressed, the nurse turned her back on me. Which was polite and appropriate. But all I could think of was, "Why bother, nurse? Do you know how many people have seen me without my clothes on in the last 16 years? Doctors, nurses, residents, technicians, probably a few janitors. The idea that it would embarrass me is absurd." I didn't say that out loud, but I thought it. The sheer ridiculousness that I got diagnosed with cancer at age 40 when I was in the best shape of my life is worth laughing it. 

I guess I write less about cancer humor these days, too, because I have a better sense of who is reading the blog. I know laughter comes to people who are open to laughter. Especially when a diagnosis is new and raw, or when things aren't going as hoped, it's hard to laugh. You have to be open to laughter before you can laugh.

I remember a few years ago, my wife and I were talking on the phone, and a friend of ours walked up to my wife to say hello just as my wife let out a big laugh. "Who are you talking to? our friend asked, and my wife said it was me. "Oh my gosh," our friend said. "I thought for sure you were having an affair and talking to your new man." She couldn't believe that y wife and I still made each laugh after being married for so long. I think about that a lot. We've been married for almost 32 years. If we stop laughing with each other, that's when I would know our marriage is in trouble. You have to be open to laughter before you can laugh. Sometimes that's just not possible for someone with cancer (but it's my wish for all of us).

So I hope you find something that makes you laugh every day, even if it isn't humor that is directly about cancer. But if you can find the humor in that, I think you're doing alright.

Have a happy day.

How Useful Are GELF Criteria?

The journal Haematologica just published a very interesting study about GELF criteria in Follicular Lymphoma. In some ways, it's a very Cancer Nerd kind of thing, but it also has serious implications for all of us as patients.

The article is called "Impact and Utility of Follicular Lymphoma GELF Criteria in Routine Care: An Australasian Lymphoma Alliance Study." It looks at 300 FL patients in a database and examines their GELF criteria, treatment decisions, and outcomes.

At this point, you are probably wondering what GELF criteria are and why they matter. GELF stands for Groupe d'Etudes des Lymphomes Folliculaires (Follicular Lymphoma Study Group), a French organization that developed a set of criteria to help determine when a Follicular Lymphoma patient needs to be treated. Because FL is slow-growing, and many of us don't need treatment immediately, the GELF criteria help to make that decision. 

The GELF criteria are:

• Any tumor mass greater than 7 cm (about 2.75 inches)
• Involvement of 3 or more nodal sites, each at least 3 cm
• B symptoms (night sweats, weight loss, etc)
• Enlargement of the spleen
• Compression syndrome (swelling that decreases blood flow)
• Pleural or Peritoneal effusion (fluid build up in lining of chest or abdomen)
• Leukemic phase (cancer cells in the blood) or cytopenias (low blood cell levels).

Having any of these issues, according to GELF criteria, means the patient has "high tumor burden" and should begin treatment immediately. To be clear, I'm not giving full information here. Go to this site and you can see more, like the exact blood cell levels that count as cytopenias.

And my giving less-than-full information is kind of part of the problem. More on that later. 

According to the article, one of the problems with GELF are how they are used. If you look at clinical trial criteria, many of them restrict enrollment to patients with high tumor burden -- meeting at least one of the GELF criteria. This is done to ensure that there is at least some kind of consistency among the patients in the trial.

The problem, though, comes when GELF is applied to real-world situations. Or not applied. 

In their analysis, they found, for example, that about 54% of patients in the study (163 of 300) were "high tumor burden," meeting one or more of the criteria. However, about 10% of those high tumor burden patients (16 of the 163) did not have treatment immediately, as the criteria would suggest, and instead watched and waited. And of the 215 patients in the study who did have treatment right away, 34% (74 of the 215) met no GELF criteria, meaning they did not have high tumor burden and may not have needed treatment right away. 

Clearly, GELF criteria are not necessarily being used by all oncologists to decide when a patient needs to start treatment. 

What's more, the study looked at outcomes, and found that, for both patients who watched and waited and for those who started treatment right away, the GELF criteria did not predict Progression Free Survival. In other words, meeting one or more criteria did not predict whether or not treatment would keep the disease in check.

The authors call for more research to try to figure out this disconnect. It's important for all of us. If clinical trials are being restricted to certain patients, there is an assumption that those patients will benefit from a treatment that gets approved. But if, in the real world, that same restriction isn't being applied to patients who receive the treatment, then that might ultimately be a waste. If patients with high tumor burden are determined to not need treatment right away, then those receiving treatment based on GELF criteria might be being treated unnecessarily.

There's another issue worth mentioning that's important to patients. I think we often see something like GELF criteria (or something like FLIPI) when we are researching our disease, and we misunderstand it. I think this happens early on, especially, soon after we are diagnosed. There are some good sites that describe GELF, like the one I link above and again here.  But there are lots of other that don't give very good descriptions. And frankly, the article I'm discussing is one of them, which gives an abbreviated list of GELF criteria without all of the important detail ("Patients required one or more of the following characteristics to be considered ‘high’ tumor burden according to GELF: any tumor mass >7 cm diameter; ≥3 nodal sites (each >3 cm diameter); B symptoms; splenomegaly; compression syndrome; serous effusion; leukemic phase or any peripheral blood cytopenias"). 

It's easy for a patient to read something like that and panic, thinking they need treatment immediately. The research in the article suggests otherwise, and that's why I tried to highlight that my own list above is not as detailed as it could be. These kinds of official lists, which try to quantify something that is hard to put a number on, make everything seem really definite. Numbers are tricky things, and they don't always represent the certainty that they seem to. A GELF number doesn't always signal a need for treatment, like a Overall Survival figure doesn't say anything about our own individual situations. Follicular Lymphoma is too heterogeneous a disease to have numbers provide any kind of certainty. It's just to different for each individual patient.

So if you're a Cancer Nerd and you enjoy diving into the analysis of statistics and outcomes, I hope you enjoy the article. But even if you're just a non-nerdy FL patient, this is all a good reminder to be careful with what you read and don't jump to conclusions about how the statistics for a large number of patients might affect you as an individual. If you read something and panic, do your best to take a step back, take a deep breath, and make a note to talk to your oncologist about it. We're all different.

Have a great day, and thanks for reading.

EB103 T Cell Therapy

I got several notices yesterday about very early results from a clinical trial for EB103, a T Cell treatment. Given the recent post here about other T-Cell related treatments, it caught my eye, since EB103 seems to work in a different way.

Interestingly, the notices I have gotten are from investing websites, not oncology websites. As I said, it's very early in the clinical trial process,  so there might not be much to report just yet on oncology sites (indeed, the notices really describe results for just one patient). Maybe we'll hear more in a  couple of months at the ASH conference.

It's also early enough in the process for EB103 that it's hard to find clear information about it, the kind that gets written for patients when it's closer to the possibility that patients will be given the treatment. So it took a little bit of work for me to understand how it works (and I'm not 100% confident that I do understand it, to be honest).

EB103 is described as "CD19-Redirected ARTEMIS T Cell." ARTEMIS stands for Antibody Redirected T Cells with Endogenous Modular Immune Signaling. 

The key word for me in understanding this is "Endogenous." T cells are a type of immune cell. They float through the blood and look for things that don't belong there, like bacteria or viruses. They attach to antigens on the cell they are looking to get rid of. And Endogenous Antigen is a type of antigen that exists within a cell. (The opposite is an Exogenous antigen, something like a bacteria, which just floats along on its own, rather than getting into a cell.)

So EB103 works sort of like CAR-T and Bispecifics in that it uses a T Cell to go after cancer cells. It has two parts. One part looks for the CD19 protein on a cancer cell. But the other part is the innovative part. It is able to treat the cancer cell as an invader by looking for the Endogenous antigen, the way a T Cell would look for a virus. Because it has two targets, the EB103 can potentially be more effective.

Maybe more importantly, because it has that second part to it, the maker of EB103 says it is less likely to result in severe side effects like Cytokine Release Syndrome, one of the dangers of CAR-T for some patients.

Their website has a short animated video that describes all of this. As I said, it's still pretty technical right now, but interesting.

The notices I have gotten describe a patient who was given the treatment in a phase1/2 clinical trial and had a Complete Response. The patient has grade 3A Follicular Lymphoma with some grade 3B symptoms. he has already had three treatments and relapsed with each. He had no severe side effects.

This is definitely one to watch, and I'll be curious to see if they present at ASH in December with some updated results. It's very early, and it would be years before this treatment was available outside of clinical trials, so there isn't much to get excited about just yet. 

But I also think it's a good example of some of the ways researchers are going beyond CAR-T and Bispecifics to use the immune system to fight cancer. And that broader trend is worth being excited about.

The Current State of CAR-T and Bispecifics for FL

Great article a couple of weeks ago from the journal Blood Advances, which is published by the folks at ASH. The article is called "The rules of T-cell engagement: Current state of CAR T cells and bispecific antibodies in B-cell lymphomas." 

This isn't giving a description of original research. It's one of those "Here's where we stand today" articles that sums up everything that's happening with a topic. In this case, it's looking at two types of treatments, CAR-T and bispecific antibodies.

If you've been a regular reader lately, you know that, at least in my view, the these are the two treatment types that get lymphoma oncologists/hematologists most excited. They have been around for a few years, so their effectiveness is pretty well-known. And there is more and more research happening to improve them in different ways, whether by finding new targets for them or reducing their side effects.

A quick reminder: CAR-T stands for Chimeric Antigen Receptor–modified T cells. CAR-T works by removing some of a patient's T cells (a type of immune cell) and changing them in a laboratory so they more easily recognize cancer cells. Then they are put back into the body and allowed to do their job. It's been a very successful treatment for many (though not all) patients. CAR-T can have some severe side effects, though as CAR-T is used more, oncologists are getting better at identifying them and trying to manage them.

Bispecifics are different. They are made up of two parts (that's why they are called "bi," meaning "two." One part seeks out a protein found on the surface of a B cell, similar to what Rituxan does. But the other part seeks out a protein on a T cell (there's that immune cell again). By bringing the T cell next to the cancer cell, it allows the T cell to eliminate it. This also can have some serious side effects, and has also been very successful for many (but not all) patients.

The article provides some of this background, but also looks specifically at which CAR-T and bispecific treatments have been approved for use with certain types of lymphoma. Of course, Follicular Lymphoma is one of those types, which is why I'm writing about it.

As the chart from the article shows, there are three CAR-T treatments approved for FL (at least in the U.S.) -- known as Axi-cel, Tisa-cel, and Liso-cel. And there are two bispecifics currently approved -- Mosunetuzumab and Epcoritamab. The chart shows which line of treatment they have been approved for (it's third line or later for all five of them, at least for now), gives some data about effectiveness (the Overall and Complete Response Rates), and some information about safety (the percentage of patients who experienced particular side effects).

It's a really nice chart (if you're into that kind of thing. And I am.)

There's also a bit of a longer discussion for each of the different types of lymphoma, and the section on FL is very interesting. 

The authors talk a little bit about sequencing of treatments. For advanced or bulky disease, they usually go with immuno-chemotherapy (something like R-CHOP or B-R, I assume), if that seems appropriate for the patient. They typically go for R-squared (Lenalidomide + Rituxan) for a second treatment. And then they express their happiness that CAR-T and bispecifics are now available for a third line, which have greatly increased the options that patients have.

I appreciate their careful discussion of third-line treatment decisions. As they say, neither CAR-T nor bispecifics are shown to cure FL, so patient choice becomes very important. And there are lots of factors to consider, from cost (CAR-T is much higher) to side effects and quality of life. They also mention that younger patients might prefer CAR-T, since there is a greater chance of it being a "one and done" treatment. Patients who have transformed might also prefer CAR-T, since it is very effective against transformed FL.

Finally, the article describes some of the current and future research happening with CAR-T and bispecifics. This includes using either of them in combination with other treatments, using bispecifics after CAR-T as a type of maintenance, and using either of them as a first or second line treatment.

As I said, it's a good article in that it brings a lot of stuff together in one place, and it's clear why these two are so exciting. I don't have a sense of whether there are other types of lymphoma treatments being developed that also use T cells to go after B lymphocytes, but my guess is that with the success of these two treatments, there are plenty of ambitious and innovative researchers who are looking.

The bottom line is, once again, that we have options, and there are more coming. That should make us all a little bit happier.