Three Factors to Consider in Choosing R/R Treatment

The website Oncology News Central posted an interview a few days ago with Dr. Ahmit Mehta, a Lymphoma specialist at the University of Alabama at Birmingham. It's called "Three Factors to Consider in Relapsed/Refractory Follicular Lymphoma Care." It runs a s a video, but there is also a transcript if you'd rather read, or you need to translate. The website is mostly aimed at oncologists and other health professionals, but I have to say, Dr. Mehta does a fantastic job of explaining things very clearly. I don't know if anyone out there is a patient of his, but I'd bet he's just as good at explaining things in person. 

I thought it was an interesting interview for two reasons. 

First, it focuses a lot on Tafasitamab, which I talked about in my last post. So it's kind of a timely video that way.

Second, he discusses the factors that he considers when he needs to help a patient make a decision about treating Relapsed or Refractory Follicular Lymphoma. Let's look at that first, since it's the title of the video.

When he was asked how he makes decisions about treating R/R FL, he said, "When the patient relapses, at that time, there are multiple factors we consider for second-line treatment. Usually, the way I think in my mind, is: Patient-related factors are number one, disease-related factors are number two, and number three (that I’ve added recently) is center-related factors."

I find this really interesting. I've seen lots of general descriptions about the kinds of factors that go into those decisions, but never in quite this way.   

First, the patient-related factors. (It's nice that he puts patients first, and not surprising if you watch the whole video). These factors include things like comorbidities -- the other health problems that a patient might have. Certain problems will mean that particular treatments are not a good idea, since their side effects can be aggressive and create even more new health problems. Second are the disease-related factors. Is the patient POD24 or showing B symptoms? An aggressive relapse might mean a more aggressive treatment recommendation.

And third is "center-related" factors. I thought it was really interesting that he added this consideration recently. Not all treatment centers offer every treatment, and something like a bispecific or CAR-T are only offered at a limited number of centers. If a patient will have a hard time getting to a treatment center, or staying at the center for a couple of weeks to be evaluated, then a different treatment might be considered instead.

Now, any decent doctor would consider all of those factors as well, and I don't think Dr. Mehta came up with all of that on his own. But I do appreciate the way he breaks it down, and how he shows the things that he prioritizes. As we consider our own treatment choices, those same factors are what we should be thinking about, or at least be prepared to ask questions about. 

The second interesting thing that Dr. Mehta talked about was Tafasitamab. As I wrote about in my last post, there are lots of Lymphoma specialists who are very excited about the newly-approved combination of Tafasitamab and R-Squared (Rituxan + Revlimid). Dr. Mehta is one of those specialists. He sees very real possibilities for Tafa-R-squared, as he calls it, becoming a very popular choice for R/R FL.

One thing I thought was interesting was that he said R-Squared was currently the most popular second-line treatment for FL. I haven't seen evidence of that, though I'm also not someone whose job it is to know such a thing. But anecdotally, it seems to me that lots of FL patients are receiving R-CHOP or B-R, especially if they didn't receive chemo as a first line treatment, as well as CAR-T or bispecifics. I wonder sometimes if doctors who work in academic medical centers, where cutting-edge treatments are developed and tested, have a different perspective on things than doctors in community clinics, where old habits tend to rule. 

Or maybe Dr. Mehta is correct, and more and more doctors are using R-squared as a second treatment for R/R FL. And if that's true, then the jump to Tafasitamab shouldn't be hard. (But, as I said last time, I have my doubts, still.) 

Overall, it's a very good video, and those of us who have already had treatment would find it very interesting. The video is about 15 minutes long, and as I said, there's a transcript available as well.

I hope you get a chance to watch or read.

Tafasitamab: New Standard for R/R FL?

I've been seeing some discussion online lately about Tafasitamab, and its promise for treating Follicular Lymphoma. There are a few people who think it could become the standard treatment for Relapsed/Refractory FL, given the success of the clinical trial that led to is approval a couple of months ago.

But all of the positive talk got me thinking more about how certain treatments get to be so popular, and why others never really seem to catch on.

Part of my thinking this ways comes from a conversation I had recently with someone about RIT (RadioImmunoTherapy). This type of treatment involves taking a monoclonal antibody (something like Rituxan) and adding a tiny amount of radiation to it. Because the antibody seeks out a protein on the lymphoma cell, the radiation gets delivered right where it is needed, so there is less damage to cells that don't need the treatment. It was all the rage when I was first diagnosed, and I know a few people who received it many years ago and who a very long remission because of it.

However, it never really caught on the United States. The rules for a treatment like this required that an expert in nuclear medicine administer it, rather than a regular clinical oncologist. To be able administer it, the doctor would need 400 hours of training (if I am remembering this correctly). So very few people received RIT, even though trials showed it was very effective and there were a few different options available.

It's an example of a good treatment not getting to patients who would benefit from it.

So when I see the headlines about Tafasitamab -- that it might be a "game changer," or a "new horizon," or a "new standard," I have to wonder if it's really going to happen. (The "game changer" headline comes from a website that uses that phrase once a week about some new cancer treatment. The articles are generated by Artificial Intelligence. That's a whole different blog post.)

The reasons for excitement over Tafasitamab are pretty clear. In the InMIND trial, the phase 3 trial that led to its approval, 548 patients were either given R-Squared (Rituxan + Revlimid/Lenolidomide) or R-Squared plus Tafasitamab. The results were great. The Tafasitamab group had an 83.5% Overall Response Rate (versus 72.4% for the R-squared group) including a 49.4% Complete Response (versus 39.8%) and a median Progression Free Survival of 22.4 months (versus 13.9 months for R-Squared). Safety was comparable to R-Squared alone. You can find a good summary of all of the side effects here.

But here's why I'm a little skeptical about Tafasitamab becoming a new standard. One of the very enthusiastic pieces I saw about this said that this new combo would be a potential replacement for patients who would be eligible for R-Squared. This makes sense, given that it was shown to be more effective than R-squared. But how many patients would be given R-Squared in the first place?

About a year ago, the Follicular Lymphoma Foundation conducted a survey of FL patients from 49 different countries. One question asked which treatments the patient had received. In that survey, only 6.2% of respondents had received R-Squared. That's not a huge number. But if that's the ceiling -- if the Tafasitamab combination is going to replace it for some patients -- I'm not sure how much of a "game changer" it's going to be for patients in general.

I want to be clear about a couple of things. 

First, and most importantly, I'm not a doctor. I remind you all of that every now and then because it's really important for you to remember. I have not formal medical training. I'm not an oncologist or a cancer biologist (or a scientist of any kind). I'm a Cancer Nerd -- a patient who reads a lot, and then thinks and rights about what I read. So why listen to me? Good question. The most important person to listen to is your own doctor. 

Second, I want to be clear that I'm not anti-Tafasitamab in any way. Just the opposite. I hope it gets to the patients who would benefit from it. I still have a lot of frustration over RIT. I think it could have helped a lot of people 15 years ago, and it was frustrating t see it not being used. (Search for "RadioImmunoTherapy" on this blog and you can see my long history of frustrated posts.)

But take another look at the FLF survey. The treatment type that most patients have had? Chemotherapy, with 60%.  

And that's not necessarily bad (it can be very effective) and it's also explainable in some ways (FL patients can live for a very long time and treatment types were limited 15-20 years ago).

But I also think it's true that FL patients can be over-treated, given more aggressive treatments than necessary. (I'm getting this from a couple of conversations with oncologists.) People get chemo who don't need chemo, and maybe could do just as well with something like Rituxan.

So why so much chemo? I  read a comment from an oncologist once that doctors are creatures of habit. If they have always recommended chemotherapy, and it has worked well, there's not much reason to change to something else. It's hard to argue with that logic. As a patient, if my doctor said "My previous patients have done really well with Bendamustine," I probably wouldn't argue.

But I think that's ultimately what this is all about. Very few of us patients argue.

And I don't really mean "argue," as in getting mad at the doctor. I mean, few of us know enough to have a conversation with a doctor that might lead to a different option. Why chemo? What are the other alternatives? Why not them? Can you recommend someone else I can talk to for a second opinion? 

It's not really about arguing so much as asking questions. And that can be hard to do when you've just been told you have cancer. 

But it's what I hope you will do, especially with Relapsed/Refractory FL, when we've had some time to think and learn and perhaps plan. We don't all have the opportunity to get a second opinion, or to question the decisions that a doctor or a health plan make for us. But if we can? That's how change comes, and how good treatments get to people who need them.

Stay informed, and stay well.

 

Happy Lymphoma Awareness Month!

September is Lymphoma awareness month. 

It's Blood Cancer Awareness month, so it's also Leukemia and Myeloma Awareness Month, too. But I think most of us are concerned with Lymphoma, so we'll stick with that.

I always struggle with the idea of "awareness" at this time of year. Like most of you, I'm very aware of Lymphoma -- my own, and of the disease in general. But this month isn't really for us. It's about helping others be more aware of it.

Part of that is encouraging others to be aware of their own bodies. That's a big part of cancer detection -- knowing when something is wrong and then getting it checked out. Lymphoma Canada has a "Know Your Nodes" quiz that's very informative. Take it yourself and encourage others to take it, too.

And if you're comfortable, share your story. You can do that with the people you know, or share it on social media, if that's something you take part in. Or you can share it through the Follicular Lymphoma Foundation's website. 

I think that's very important. There was a time, not too long ago, when people wouldn't even say the word "cancer." It made cancer seem like a shameful thing. That led to all kinds of problems -- people not going to the doctor even if they suspected something was wrong. Isolation after diagnosis and during treatment -- exactly the time when patients needed others. And then the weird gilt that so many of us feel. Silence isn't good, at least in general. But as I said, share your story if you're comfortable doing so. There's no sense in making yourself feel worse by doing something you don't want to do.

And, of course, continue to educate yourself. Learn all you can about the disease. Not everyone wants to do this, and I understand that, too. I had an oncologist who told me that some patients didn't ever want to hear anything about the disease -- just did everything the doctor said. I get that, too. I had a loved one with cancer (not a blood cancer) who just couldn't stand the idea of doing any kind of research, for lots of reasons. But if you're here reading this, you're probably someone who likes to be informed. So keep that up -- keep finding good sources of information about FL and learning what you can. I'm always happy to share what I know on this blog, and to help people be informed, but remember that I'm not a doctor, and the best source of information is your own oncologist.

Still, there's much that we can teach one another, so I always recommend listening to other patients who can provide good information. 

I recommend The FL Community Podcast, which I wrote about last month. Their latest episode is available now. The hosts focus on Managing Treatment Side Effects in this episode, discussing common FL treatments and the typical side effects that come along with each. Nicky, one of the hosts, is a clinical nutritionist, specializing in oncology patients, so she offers some tips on eating well to manage particular side effects. This is a great example of what I mean about awareness -- well-informed patients telling stories and offering advice based on real experience. It's the kind of information that we often forget about when we are planning for future treatments. 

I hope everyone has a great month. Do something extra to increase your own awareness, and to share your knowledge with others. And be sure to do something to treat yourself -- a walk in a favorite place, or a meal that makes you happy, or a day off from work -- something that brings you joy. You deserve it.

Stay well. 

Predicting POD24 in Follicular Lymphoma

 Great research from the journal Blood last week, an article called "Combined PET and ctDNA response as a predictor of POD24 for follicular lymphoma after first-line induction treatment."

Actually, two articles. The second is a commentary on the first, and might be even better, since it gets into why the first one is so important. The second is called "Cracking the POD24 code in follicular lymphoma." 

As you can see from the two titles, this research focuses on POD24, or Progression of Disease within 24 months of receiving immunochemotherapy (like B-R or R-CHOP). When POD24 was first discovered, it was a big deal. There was finally a way to quantify a particular risk, and what that risk was. Basically, a patient labeled as POD24 received immunochemotherapy, responded to it, but had the disease come back within 24 months. (In the way it was originally formulated, POD24 doesn't apply to patients who had other treatments besides immunochemo, but I've seen it used for other treatments anyway.) This matters because POD24 patients have a statistically lower survival rate than the rest of the FL population. About 20% of FL patients are POD24.

The problem is, there is currently no reliable way to predict POD24.  The work I wrote about recently on subtypes might prove useful some day, but for now, there's no way of knowing someone is POD24 until they receive treatment and the disease comes back. Lots of FL researchers say this should be a priority in the FL community (I tend to agree). 

This research is an attempt to predict POD24 after the immunochemotherapy treatment.

As the chart in the second article shows, the tools we have now for predicting POD24 are pretty bad. They're very good at negative prediction, meaning they can tell us which patients are not POD24. But they are bad as positive prediction -- none of them are right more than 50% of the time. It's a flip of the coin. Or a FLIPI of the coin. (I hope at least one of you laughs at that, because it was an excellent joke.)

Two of the tools used to predict POD24 are PET scans and ctDNA MRD. We're probably all familiar with PET scans. They measure how much of a sugar solution is taken up by hungry cancer cells. If you're a patient with FL, you've probably had at least one. 

ctDNA MRD means circulating tumor DNA Minimal Residual Disease. It measures the presence of cancer differently from a PET scan. Using some very sophisticated tools, the amount of cancer can be measured in the blood. It might be so tiny that a PET scan won't detect it. But if there is ctDNA still in the blood after treatment, it means the cancer was not completely taken care of.

As a predictor of POD24, a PET scan after initial treatment was able to predict POD24 about 45% of the time. ctDNA MRA was better -- it could predict POD24 about 58% of the time.

But the researchers in this article innovated by using both tools. When combined, they predicted POD24 about 85% of the time. Obviously, a huge improvement. And any improvement in predicting POD24 is great for new FL patients.

However, as that second article points out, the practical applications of this knowledge are a little complicated.

The problem comes from when the tests are given -- AFTER treatment. 

If a clinical trial was conducted using this information, it would be run by first having a group of patients receive initial treatment -- let's say Bendamustine + Rituxan (to keep it as immunochemotherapy). If any patients were identified as POD24 with the PET + ctDNA tools, they could then be given a second treatment right away, something like CAR-T or a bispecific, both of which have been shown to work very well on relapsed or refractory FL. This could happen before the disease even came back officially (remember, it could take up to 2 years for the disease to show up again).

The problem is, it would be expensive and complicated to set up a clinical trial that gives that set up something as a comparison. In other words, it might be too complicated to show that the testing is better than what we have now.

Ideally, we'd have a biomarker that shows us POD24 BEFORE that initial treatment. To be clear -- this is a step forward. Anything that predicts POD24 accurately, even at this stage, is an excellent thing. Catching the cancer early might save a lot of lives.

It's another small step forward, and moving forward is what we want. 

Stay well.

Seeing Yourself in Others

A few days ago, I had the wonderful opportunity to be in a Zoom meeting with a bunch of other patients with Follicular Lymphoma. There were about 15 people on the call, and my math might be off, but I think we came from and/or lived in 7 different countries. It's never easy to find a time where people from different parts of the world can conveniently meet, but I'm very glad the meeting happened and very grateful that I was invited.

The meeting was set up by the Follicular Lymphoma Foundation, and the participants were Super Supporters, a group of patients who provide insights and ideas for the foundation. 

I won't get into details of the meeting or who was there, but I do want to share how I felt afterwards.

If you've never had the opportunity to meet with a group of FL patients, or cancer patients or survivors in general, I hope you'll seek out such an opportunity. There's something really wonderful about seeing yourself in others, and hearing their stories. Everyone with cancer has a unique story. And that's especially true for a cancer like Follicular Lymphoma, which is known to be heterogeneous, taking many different forms. Everyone on the Zoom call had a different experience. 

But at the same time, there was so much that we had in common. We share the same fears, sometimes the same guilt. Many of us were surprised by our diagnosis. Many of have dealt with the same short-term and long-term side effects. For all our differences, we have a lot in common.

And it's a strange experience to hear your story mirrored in someone else's.

I remember years ago being part of a face-to-face group of cancer patients and survivors giving some feedback on a cancer-related website. Our meeting started with everyone introducing themselves. The introductions went on for a while, with people sharing lots of details about their stories. I remember one patient in particular who had been diagnosed with a particular cancer (not FL), but the diagnosis took several years to finally settle on cancer. This person was told it was a type of cancer, then told it was a different kind of cancer (a less worrisome type), then told it was a third different type (a more worrisome type), and then told that it wasn't cancer after all, but a different condition, and then finally the cancer diagnosis that proved to be correct.

As they told the story, everyone in the room went on this roller coast ride with them. You could see it in everyone's faces, including mine -- hopeful that the diagnosis was the right one, then frustration and sadness that it wasn't, then anger that they had been given wrong information, and then hopefulness again.

I can't describe accurately what it felt like to hear this person's story. Despite all of those negative emotions -- frustration and sadness and anger -- when they finished, I felt this overwhelming positivity. It wasn't just relief that they finally got an accurate diagnosis. It was a feeling of connection -- of knowing that, even though my story was different, we were connected in ways that other people just couldn't be connected. It's not the same to hear a doctor tell someone else they have cancer as it is to hear it said about yourself.

I felt  similar way after the FLF meeting. Everyone;s story was different, and while we didn't share our stories in the introductions, those details came out as we talked over the course of 90 minutes. Cancer can be isolating sometimes. Connection is a great thing.

At the same time, I was keenly aware of the differences. And that was a great thing, too. I've been living with Follicular Lymphoma for over 17 years. I had a very particular experience when I was diagnosed, watching and waiting for 2 years. I was relatively young -- 40 years old. My kids were 6, 8, and 10 years old. I had 6 rounds of Rituxan as treatment. I've dealt with long-term side effects related to my heart and my skin. I'm a Follicular Lymphoma patient advocate, blogger, and freelance writer. I have thought about FL literally every single day since I was diagnosed. What's more, I actively seek out information about FL -- every day. I don't push it out of my head. I pull it in.

And that's all very different from most other patients' experiences. And hearing those differences reminded me of how important it is for me to recognize, think about, and understand those differences in experience, especially if I am going to call myself a Follicular Lymphoma patient advocate. If my goal is to help lots of people, I need to remember that not everyone thinks like me, or acts like me, or wants the same things.

So, as I said near the beginning of this post -- if you've never had the opportunity to meet with a group of FL patients, or cancer patients or survivors in general, I hope you'll seek out such an opportunity.If feels good to share your story, and it feels good to see yourself in others' stories. Maybe that means finding a face-to-face support group at your cancer center or somewhere else near you. Maybe it means finding an online group, as I did when I was first diagnosed. There are some good ones online, including the Facebook groups Living with Follicular Lymphoma, Linfoma Folicular Grupo, and Young Adults Living with Follicular Lymphoma. The new FL Community Podcast is explicitly about sharing stories, and is going to be an excellent resource for a lot of people.

And if you want to share your own story, I recommend going to the FLF website and providing some details. You can read others' stories, too, and maybe see yourself in others. And with a little luck, you'll capture that same feeling of being connected that I have been able to feel. 

As much as I wish it wasn't true for any of us, we're all kind of in this together. We can help each other out even in the smallest of ways.

Take care of yourselves.

New Research on Follicular Lymphoma Subtypes

The journal Cell Reports Medicine has a very interesting article this month, reporting on some research that might have significant implications for those of us with Follicular Lymphoma.

The article is called "Whole-genome sequencing reveals three follicular lymphoma subtypes with distinct cell of origin and patient outcomes."

Basically, the article is suggesting that Follicular Lymphoma is not one disease, but three different subtypes. Those three subtypes have different outcomes, and would require different treatments. The idea that FL isn't just one thing really is not new. As I wrote in reviewing an ASCO presentation, FL is considered heterogeneous -- it shows up in each of us a little differently. That makes it tough to figure out how to treat it. There have been many attempts (including that ASCO research) at finding biomarkers to help with this -- some kind of biological signal that will help guide treatment decisions. So far, those attempts haven't been completely successful.

That's where we are with this research. It describes an attempt at finding gene-based biomarkers that will guide treatment for Follicular Lymphoma.

First, some more background about where the study is coming from. Cancer research took huge steps forward when the human genome was finally mapped about 25 years ago. The human genome is the complete set of all 62 million or so genes in a person's DNA. Mapping out the genes is a first step. Once researchers knew where they were, they could start to examine what happened when they were damages, or switched places, or did things they weren't supposed to do.

Cancer researchers have been trying to use this knowledge to develop new treatments since that time. A well-known example is HER2-positive breast cancer. HER2 is a protein that is the result of someone having extra copies of a specific gene. It can result in a type of aggressive breast cancer. There are now treatments that can target this type of breast cancer, and the prognosis has greatly improved as a result.

I'm using breast cancer as an example because, so far, we don't really have that kind of success story for FL. There aren't any reliable biomarkers to guide research and treatment. 

And that's what this research is hoping to do -- identify biomarkers that can distinguish different subtypes of Follicular Lymphoma.

The early results of the research look good, hough, as I'll explain, I'm still a little skeptical.

(And this is a good time to give you the reminder that I give to you frequently -- I am not an oncologist or a cancer biologist. I'm just a Cancer Nerd -- a patient who reads a lot. Keep that in mind, always.)

The researchers looked at 131 samples from FL patients from China and conducted Whole-Genome Sequencing (mapping out the entire DNA of each sample so they could be compared to one another to see how they were specifically different from one another). They determined that there were 3 different subtypes, based on differences in the DNA. Recognizing that there are possible differences based on geography, they repeated the same process with 227 samples from outside China, and found the same results.

At the risk of being too general, I'm not going to get too heavily into the details of what they found. Genetics is fascinating, and if you want a deep but understandable introduction, I recommend The Gene: An Intimate History, by the oncologist Siddhartha Mukherjee. If I got too much into the details of the genes, I'd mix up you and me both. Here's a sample from the article: "K1 is related to the activation-induced cytidine deaminase (AID) activity and is enriched in activation B cell-like (ABC) DLBCL, whereas K2 is associated with POLH activity and is enriched in GCB-like DLBCL.The majority of the kataegis events were concentrated in specific genomic regions, notably the IGH, IGK, and IGL genes, along with the transcription start site (TSS)-proximal regions of genes such as BCL2, BCL6, BCL7A, CXCR4, and BTG2." I lost track myself of which gene or protein they're talking about.

More important are the results -- the three subtypes that they are proposing.

They call them C1, C2, and C3.

C1 is high grade (fairly aggressive) but has a ow risk of POD24 (the disease returning within 24 months after successful treatment), and has a good Progression Free survival (a long time between treatments). 

C2 is low grade (less aggressive, probably more likely to watch and wait), with low chance of POD24, and moderate PFS. 

C3 is high grade, with a high chance of POD24, and poor PFS.

Looking at those differences on the surface, they seem to capture FL patients pretty well. It's a heterogeneous disease.

The details of how they got to these three categories are interesting, though pretty dense. They provide a very convenient chart in the article (Figure 7, if you want to take a look yourself).

 Each of the three types has its own biomarkers. C1, for example, is more likely to have BCL6, or the B Cell Lymphoma 6 gene (as well as a few others). There seem to be differences in the Tumor Micro-Environment for each type as well (this is what is happening in the area around the cancer cell, which can be just as important as the cancer cell itself). C1, for example, tends to have "hot" tumors, meaning there are lots of immune cells in the tumor. This means it is more likely to respond well to immune therapies, for example.

The summary for all of this is that the researchers did a bunch of different tests on the genome to figure out which genes were different and why that mattered, and then suggested that certain treatments would work on the different subtypes based on those differences. C1 may respond well to PI3K inhibitors, BTK inhibitors, IRF4 inhibitors, and immune therapies. C2 may respond well to BCL2 and EZH2 inhibitors. C3 may respond to PI3K, BTK, IRF4 inhibitors, but not immune therapies.

It's all very encouraging. The testing they did was pretty extensive, and the fact that they tested it on a second cohort helps to make their results more encouraging still. 

But as I said, I'm skeptical. Maybe "skeptical" is the wrong word here. I don't doubt their results. But I've been following the search for FL biomarkers for 15 years, and I haven't seen any real results yet. Maybe this will be the one that gives it to us? Or at least moves us on that path?

As a start, it's going to take a much larger sample with the same results to really get the attention of the Lymphoma community. Then there will have to be actual trials, where a large number of FL patients are divided into subtypes, and then treatments are given to them based on their subtype to see if, for example, the EZH2 inhibitors really do work better than an immune therapy for the C2 patients. 

It's going to take come time to test all of this out. Years.

But that's OK. I can wait.

I am encouraged by it, and hopeful. It all makes sense. Some patients in a trial respond really well to a treatment, and some don't respond at all. They were all put into the trial based on having some things in common. But maybe the traits that they have in common aren't the ones that matter. Maybe this research has identified the things that really do matter.

I'll definitely keep an eye on this one. It's been published in a peer-reviewed journal, so it has been seen by other experts, which means it is less likely to be presented at a conference like ASCO or ASH. But an update to the research cold be presented there. 

I'll keep looking. You keep hoping. 

 

 

Oncologist Appointment

I had a 6 month oncologist appointment today. Everything looks good.

**********

A quick comment before I get to the details of the appointment. 

When I came out the office, I had a text waiting from my wife. I responded, and also let her know that everything looked good on the cancer front. My kids were 6, 8, and 10 when I was diagnosed. They're 24, 26, and 28 now. But even when they were small, my wife and I made it a point to be completely honest with them. We knew that if we hid anything from them, even small kids were going to figure out something was wrong, and probably imagine the something even worse than the truth. So the Full Transparency Policy has staid in effect. I text them after each appointment.

But then as I was walking to my car, I thought I should tell my kids the good news, too. I started to text them, and stopped myself. What I started to say was "I had an oncologist appointment this morning. Everything looks fine."

But here's the thing -- they didn't know I had an appointment. So even the small shock they might in that little space between "I had an oncologist appointment" and "Everything is fine" was something I wanted to avoid.

So I flipped it and reversed it, as Missy Elliott would say. "Everything was fine at my oncologist appointment this morning." Start with the good news. Don't leave them guessing.

And yes, I know I don't start with the god news when I write to you all, like I did with this post. But I know you're living with this every day. You can handle it.

I'm always fascinated by the ways we use language to talk about cancer. Maybe I was overthinking that text to my kids. But I know how much impact words can have sometimes. 

**********

Back to the appointment.

As usual, my 6 month appointment involved blood work, a physical exam, and my own reporting on how I was feeling.

I'm feeling fine, at least as far as cancer goes. No new swollen nodes, which the doctor confirmed with his exam, and no B symptoms. My bloodwork is normal.

We always have a good chat about what's going on in our lives, since there aren't too many health concerns to get into. We talked about travel, and our separate experiences in Philadelphia and Syracuse (my wife and I visited both places this summer). The doctor recommended a good Barbecue place in Syracuse -- we somehow always end up talking about smoked meat.

As far as my cancer goes, he said it was "remarkable" that I have gone 15 years with just the Rituxan. He thinks there is a chance that I won't ever need treatment again. (That's a wonderful thought, and while I try to live my life as if that was the case, I also refuse to believe that it's true.) Interestingly, he said that if I had signs of lymphoma again, he would want to basically start from scratch -- doing a biopsy and everything else at diagnosis to know for sure if it was Follicular Lymphoma. That makes sense, and it's what I assumed would happen. But this is the first time he's kind of suggested that it might not be FL, if I do get another diagnosis.

As always, I asked if there was anything new and exciting with treatments. He is still very excited about bispecifics. He said they working very well for a lot of patients, though there are still concerns about side effects. When a patient is treated with bispecifics at the cancer center that I go to, they are admitted to the hospital, in case there are any problems. He thinks newer generations of bispecifics will be safer, with fewer severe side effects. This will make them more widely available, with treatment in a doctor's office and not in a hospital. Very interesting.

So that's my update. I'm still healthy, as far as Lymphoma goes. My wife ad kids have been informed. Traffic and the parking garage at the cancer center are still awful. My doctor is great but sometimes forgets to put in the blood work order. Overall, everything looks good.

We're in the summer doldrums when it comes to Lymphoma research. All the good stuff was presented at ASCO in June. I'll keep looking for good things to share. If I can't find anything soon, I may have to start sharing pictures of my dog instead.

Stay well.

Epcoritamab + R-Squared: Interim Results

The makers of the bispecific Epcoritamab just issued a press releasewith some interim results from the phase 3 clinical trial for Epcoritamab and R-Squared (Revilid + Rituxan) for Relapsed/Refractory patients with Follicular Lymphoma. The press release points out some very good news. The combination has an Overall Respose Rate of 95.7%, an improvement over R-Squared alone (which has an ORR of 89%). It also had a higher Progression Free Survival; it "reduced the risk of disease progression or death by 79%."

The plan is to present the results at the ASH conference in December, where they will present all of the data. The FDA agreed to a priority review of the combination last month, meaning they should issue a ruling by November 30 (which would be before the ASH conference).

All of this sounds great, but I have some questions. And, to be clear, I'm not suggesting anybody is doing anything wrong.

Te press release gives very little detail. And there's a good reason for this -- they're holding off on releasing any details until the ASH conference, which makes sense. This is a "scheduled interim analysis," meaning they had planned to look at the results they had so far at this point in the trial. Because they haven't competed the trial, they don't want to give too much detail yet.

The other side to all of this is that they need to keep investors happy. A little good news will do that, and a fairly general statement with some plans for the future won't hurt either.

But for me, it all raises more questions than it provides answers. Last year, there were some safety concerns about Epcoritamab, though they were explained by the trial taking place during the Covid pandemic, when some trial participants had lower immunity which caused some side effects. The press release here says that there were no new safety issues with this combination -- only the side effects that were already known for the three different elements. But if there were already some concerns, saying this doesn't really answer the initial questions about safety.

Again, I'm not saying anybody is doing anything wrong. For me, this isn't really an issue with Epcoritamab or its makers. It's more about frustration with the larger system for approving treatments, and the place of the patient in it all.

I'm looking forward to the ASH conference, so we can see more of the data that this FDA application is based on. I have little doubt that the data presented will be positive and encouraging for patients. I hope my questions and concerns are answered. I just wish that I didn't have to have so many of them along the way.

FL Community Podcast

As you know, I'm a big fan of  two things when it comes to Follicular Lymphoma -- getting as much good information as possible, and patients sharing their stories.

So I'm excited to let you know about a new podcast related to Follicular Lymphoma called The FL Community Podcast. It's made by FL patients, for FL patients (and anyone else ho wants to know more about the experience of living with the disease).

The hosts of the podcast are Nicky Greenhalgh and Paul Mollitt. Nicky started the Living with Follicular Lymphoma group on Facebook, and Paul started the related Facebook group for young adults. If you have watched the webinars from the Follicular Lymphoma Foundation, you've seen both of them featured as patient voices in the last few months. Nicky is a clinical nutritionist, specializing in working with patients with cancer, and Paul is a psychotherapist. So they're bringing both personal experience and professional expertise to this podcast. Expect a lot of talk about some of the survivorship issues that have been so important to me lately -- mental health, nutrition, exercise, etc. 

The first episode focuses on "Initial Diagnosis," and their guest is Nicola Attfield. All three of them share their story of being diagnosed with FL, and the shock that came with it, and the emotions surrounding that diagnosis. Their experiences are different from one another, but recognizable to many of us. I won't get into detail, because I think it's important for you to listen for yourselves. It's about 49 minutes long, and worth the time.

As I said, I think sharing our stories with one another is really important. This podcast is different from a lot of what I usually share with you, which tends to focus on things like presentations at medical conferences or articles in medical journals. And obviously, that kind of information is important for us to have. It lets us informed conversations with our doctors.

But just as important is hearing from other patients. I think it helps us feel less alone. As unique as all of our stories are, there are many things that we share, too, and hearing that someone else was shocked at a diagnosis because they felt no symptoms, or that they feared for their kids, or that they went into a depression right afterwards -- it's comforting to know that someone else had that same experience.

I think it's fantastic that there are so many more accessible sources of information about Follicular Lymphoma like the FLF webinars and this podcast. When I was diagnosed 17 years ago, there was very little of this. I found a Non Hodgkims Lymphoma support group online, which was wonderful for me. The folks in the group had been diagnosed with many different kinds of NHL, including FL. But that led to some tension sometimes, too, as people brought up certain subjects that didn't pertain to everyone.

So at times, I was reluctant to share with the group, especially good news. My feeling was that if I had just had a diagnosiversary, it might make someone feel bad that I was doing well and they weren't. But what I found was the opposite -- when I shared that I had been diagnosed 5 years before, it made people happy to read. I was kind of a role model. People knew it was possible to make it to 5 years. 

So there are lots of reasons to share our stories. And this podcast will be a great way to do it.

So watch the first episode, and think about the kinds of subjects you'd like to hear them address. Their email is available by going to their channel's page. You can let them know what you'd like to hear more about.

I hope you enjoy the podcast, and continue to listen to them. I think it's going to be a very helpful thing for us all.

Looking Back

If you're on Facebook, you might have experienced its "memories" feature. Sometimes it will send you a notification letting you know that, for example, five years ago on this day, you posted something. And then it will share the post with you, and give you the option of sharing it on your page and making it public.

I rarely post on Facebook these, days, though I visit it pretty much every day. A few days ago, it gave me a "memory":

I remember this picture very well. It was taken at a family reunion in West Virginia 16 years ago, and the person whose face is blocked out is a family member that I enjoy spending time with a lot. It's a very happy memory (and not just because there is so much less white in my beard than there is now).

If you've been reading the blog for even a few months, you might know that I was diagnosed  with Follicular Lymphoma over 17 years ago. So this picture was taken about 18 months after my diagnosis.

When I got the memory from Facebook, I texted the person in the picture. "We look so young, " I said. "And I still have that shirt." She laughed and told me that she still had that blue hoodie. 

I was still watching and waiting. It was about 6 month before I started treatment. I've kept that shirt for so long because it has the name Jon Lester on the back. Lester was very important to me (and still is). He was a pitcher for my favorite team (I grew up in Boston), a Lymphoma survivor, but more importantly, he played a key role in helping me explain my diagnosis to my kids. My oldest has always been a baseball fan, and even at 10 years old, he knew about Jon Lester's cancer history. So when I was diagnosed, I told him that it was the same kind of cancer that Jon Lester had, and it helped him see things more positively. (Lester had a different, more aggressive type of Lymphoma, but the details didn't matter at that point. What mattered was that my son knew Lester had cancer, got treatment, and came back to help the Red Sox win the World Series in 2007. 

And if you want to now how important Jon Lester was to me, especially in the years right after diagnosis, then enter "Jon Lester" in the search box at the top of the blog. He shows up in 20 (now 21) different posts over the years.

I wore that shirt to all of my treatments, too. It was my uniform -- my red Jon Lester shirt, an orange long-sleeved "Life Is Good" shirt, an d a pair of dark blue Adidas sweat pants. Very comfortable. And I still have all three items of clothing. I remember going back to the oncologist's office for a follow-up visit soon after I was finished treatment, and having to use the bathroom in the treatment room. I had just come from work, so I was dressed a little better than my old shirts and baggy seat pants. I saw my treatment room nurse and she didn't recognize me. That tells you how sloppy I looked in my treatment uniform. But I was comfortable.

**********

Memories are a funny thing. And I don't just mean the Facebook kind. It's very easy to see a photo from 16 years ago and remember the great things. Long conversations with a favorite family member. White water rafting on the New River. Massive games of touch football and wiffle ball. Hanging out in a hot tub after the kids are in bed. Looking at that picture brings back all of those wonderful memories and more from our week in West Virginia. 

But not all memories are happy ones, and goodness knows those of who have been diagnosed with cancer have some not-so-happy ones. 

It's tempting to tell you to ignore the bad ones and focus on the good ones.

I certainly have been doing that here. I didn't mention the speeding ticket I got, or the sheer panic we felt when our raft tipped over and our 7 year old starting floating down the river on her own, or the fights between family members that week.

And as happy as my Jon Lester shirt makes me feel now, I didn't mention that I was wearing it when I had an allergic reaction to my first dose of Rituxan. Or when I would lie in bed after I got home from treatment, clutching my stomach from the horrible sharp pain I'd feel afterwards, until I feel asleep from exhaustion. Or the deep depression I felt, starting a few days after I invoked Jon Lester's name to my baseball-loving son, wondering what would happen to him if I wasn't around.

I don't think we should forget those things. 

Not because they were in any way enjoyable. But because we're still here to remember them.

Our memories aren't just souvenirs of the past. They're reminders of all we've been through. And of all we are able to go through and still make it out to the other side. 

Don't forget the past. But don't dwell on it either. Treat your memories like an old t-shirt. Tuck them away in a drawer. But don't lose them. Don't forget they are there. 

Use them to remember just how strong you are.

EHA: BMS-986458 for Follicular Lymphoma

As I have mentioned before, late May and early June is typically a busy time for Follicular Lymphoma research, with presentations at ASCO. (Though this year was kind of a less busy year for FL). But soon after that, in mid-June, the European Hematalogical Association's conference on Lymphoma takes place in Lugano, Switzerland. I don't usually hear as much about that conference, so I don't write about it as much. But there have been some interesting results coming from it this year.

One presentation that I have seen several stories about was called "BMS-986458, A FIRST-IN-CLASS, BIFUNCTIONAL CEREBLON-DEPENDENT LIGAND-DIRECTED DEGRADER (LDD) OF B-CELL LYMPHOMA 6 (BCL6) IN PATIENTS WITH RELAPSED/REFRACTORY NON-HODGKIN LYMPHOMA: INITIAL PH 1 RESULTS."

The presentation describes the very early results of a phase 1 clinical trial, so there's certainly no guarantee that this research will ultimately be successful. (Remember that less than 10% of cancer treatments that enter clinical trials are eventually approved.) But it's a very different kind of treatment, and worth writing about and keeping an eye on.

The treatment is currently known as BMS-986458, though it will eventually have a name that's easier to remember if it keeps moving forward. BMS-986458 is "oral, highly selective bifunctional cereblon-dependent LDD of BCL6."

There's lots of unpack there.

First, let's look at the target for this treatment, BCL6. As the leader of this research says in an interview about the presentation, BCL6, short for B Cell Lymphoma 6, has been a target for Lymphoma researchers for a long time. It is a protein that is connected to the BCL6 gene. The main function of BCL6 is to make sure B Cells (the cells that are cancerous in FL) can change so they can recognize invaders like bacteria or viruses. The B Cells can recognize an invader, fight it off, and then die. But if something happens to BCL6, then the B Cells can grow without apoptosis -- the natural process that results in the cells dying. No dying means they continue to grow uncontrolled, and uncontrolled cells means cancer, in the case FL or Diffuse Large B Cell Lymphoma or some other kind of B Cell Lymphoma. 

So BMS-986458 is meant to find cancerous B Cells by focusing on the BCL6 protein. It "degrades" or breaks down that protein, and since that protein is necessary for cell growth, the result is apoptosis -- the cell dies the way it is supposed to.

In the small phase 1 study that is described in the EHA presentation, BMS-986458 was given to 22 patients, including 13 with DLBCL, 3 with high-grade B-cell lymphoma with MYC and BCL2 rearrangements, and 5 with Follicular Lymphoma. A total of 13 patients were evaluated after a median of 2.4 months. 7 of them had a Partial Response and 3 had a Complete Response to the treatment. 

The primary goal of a phase 1 treatment, however, is to evaluate safety -- to figure out the best dose of a treatment while causing the fewest side effects. Safety was good -- there were no grade 3 or greater Adverse Events, which is very encouraging. However, one patient had to leave the trial because it seemed to affect a different health issue and another had to have the dose reduced because of side effects. In all 4 of the patients who were not evaluated had to leave the study because of adverse events/side effects. 

The early results are very interesting. Definitely worth keeping track of. The lead researcher said in that interview that combining BMS-986458 with bispecifics or monoclonal antibodies seems like a logical next step, since the combination would work against the cancer cells in different, hopefully complimentary ways.

But they are very early results. Lots can happen as the trials move forward. But it's good to be hopeful.

FLF Webinar: Charting our Progress Towards a Cure

The Follicular Lymphoma Foundation held a webinar a couple of weeks ago called "Charting our Progress Towards a Cure." It's an excellent webinar -- lots of information and lots of things to think about. 

The webinar provides some updates on FL research from a symposium that the Foundation sponsored at the 18th International Conference of Malignant Lymphoma (ICML) in Lugano, Switzerland last month. The ICML is one of the most important Lymphoma conferences in the world, and for the last few years, the FLF has held an event like this that provides up-to-date information for doctors about Follicular Lymphoma. 

Among the topics that the Expert Speaker, Prof. Jessica Okosun of Barts Cancer Institute in the UK, discusses are CAR-T, Bispecifics, and combinations that use multiple treatments together to target the FL cells in lots of different ways. The goal is to give patients the longest Progression Free Survival possible.

Prof. Okosun gives a very optimistic overview of several newer treatments and treatments in trials now. There are enough newer treatments in the pipeline, she says, that in 5 to 10 years, we may not even be using traditional chemotherapy or Rituxan anymore. There may be enough advances that these "old" treatments have been surpassed by newer, more effective and safer treatments.

And that brings up an important topic, and really the focus of the webinar -- the idea of curing Follicular Lymphoma. It's a controversial topic, in some ways. FL is still considered by many to be incurable, which means there are lots of treatments that can put the disease into remission or partial remission or keep it stable, but not necessarily wipe it out permanently. Individuals might be "cured," but not enough patients are in that situation that the entire disease is considered curable. 

When I say the idea of a cure is controversial, I mean that there are disagreements about whether or not that's true. There are some experts that say patients can be cured outright. There are others that speak about a "functional cure," meaning that a patient might not be technically cured, but are living with the disease for many years (perhaps the rest of their lives) without needing treatment.  

Part of what makes this all so difficult is that we can't say for sure what the future holds. We don't know if the disease will come back for any individual. I'll give a very personal example -- me. I haven't needed treatment in 15 years. But I also haven't had a scan in many years, and the last time I had one, there was still some evidence of the disease being present. Am I cured? Was this a "functional cure," since I'm living for so long without treatment? 

Personally, I don't consider myself "cured." It's always in the back of my mind that it might come back. 

But I live my life in many ways as if I'm cured. I have long-term plans for my life. I don't act like it's going to come back, even if I acknowledge the possibility. I think it's a good way to live.

In addition to the Expert Speaker, the webinar also features a patient speaker, Paul Christopher Mollitt. He does an excellent job of talking about what a cure would mean to him, and also talks about how he has made treatment decisions since her was diagnosed in 2017. (And he let viewers know that he was recently declared in remission after Bendamustine and Rituxan!!!!)

There's a third speaker for the webinar, Dr. Mitchell Smith, the Chief Medical Officer for the Follicular Lymphoma Foundation. If you've attended or watched these webinars, you know what an excellent job he does of moderating the discussion, connecting ideas from the speakers, and answering questions. 

There's a lot more detail in this webinar, especially about some of the very interesting research that came out of the ICML conference. It's certainly worth spending the hour or so that it takes to watch the entire thing. Lots of good information, and lots of reasons to be hopeful. 

 

Two Upcoming Webinars

I like to highlight webinars or other educational events that I think will be useful to us, and the Lymphoma Research Foundation has a couple of events coming up that are worth highlighting.

The first one is happening next Tuesday (July 22) at 1:00pm Eastern. It's called "Understanding Immunotherapy for Lymphoma (CAR T-Cell Therapy, Bispecific Antibodies, & Antibody-Drug Conjugates)." The webinar will give an overview of Immunotherapies; discuss when Immunotherapies are appropriate; look at Clinical Trials; and give advice about managing side effects. There will be time for questions and answers.

The webinar will be run by two Lymphoma experts, Dr. Samuel Yamshon of Weill Cornell and Dr. Justin Kline of The University of Chicago.

You can register for the webinar here.  This isn't specific to Follicular Lymphoma, but it should give a good overview of some of the treatments that Follicular Lymphoma experts seem to be most excited about. 

A second LRF event is also not specifically about Follicular Lymphoma, but might also be useful to many of us.  It's called "Ask the Doctor About Lymphoma: Information for Relapsed/Refractory Patients," and it's happening Wednesday, July 30 from 4:00 to 6:00pm ET.

LRF's "Ask the Doctor" series is just what it sounds like. It begins with a presentation from a Lymphoma expert, giving information about a topic (in this case, Relapsed/Refractory Lymphoma, with a focus on symptoms, treatment options, and what to ask your health care team). But "Ask the Doctor" sessions are twice as long as the other webinars, and spend much more time on Questions and Answers. So this is an excellent opportunity to get specific information from an expert.

The expert who will presenting and answering questions is Dr. Boyu Hu of the University of Utah. You can register for the Ask the Doctor event here.

(And for those of you who have not yet had treatment, and feel like you're missing out, there's an Ask the Doctor event for you next month -- "Ask the Doctor About Lymphoma: Information for Newly Diagnosed Patients." Read more about it here.)

I hope you find this information useful. 

Keep learning and stay well.

Some Analysis on Tafasitamab (Monjuvi)

CURE magazine has a nice interview with Dr. Christina Poh of the Fred Hutch Cancer Center about Tafasitamab. 

As you might remember, Tafasitamab was recently approved by the FDA, in combination with R-Squared (Rituxan and Revlimid/Lenalidomide), for Follicular Lymphoma. I wrote about this recently, looking at the the announcement from the FDA. 

But Dr. Poh offers some more insight into why this approval is so significant. Some of it came out in the FDA announcement, but hearing it from a hematologist/oncologist at a prestigious cancer center is even better.

For example, Dr. Poh points out how great the design of the clinical trial was. It's a double-blind study, meaning half of the patients in the trial receive one treatment, and the other half receives a different treatment. This allows for a direct comparison between the two. But more importantly, as a "double blind" study, it means that neither group knew for sure which of the treatments they were receiving. Knowing the treatment (which happens in lots of trials) can influence how a participant feels. If they know a treatment may cause a certain side effect, the patient may "feel" that symptom and ask to pull out of the trial. That's not a criticism of the patient -- any trial participant has the right to pull out of the trial for any reason at any time. But it's one example of how a double-blind study can be more significant. 

Another element that Dr. Poh points out is that the population more accurately mirrored a "real world" population. Many trials for newer treatments have strict limitation on who can participate in the trial. It's for a good reason. If a new treatment might affect a patient's heart, for example, then patients with heart issues are kept out of the trial. If they did participate and then had heart issues, it would be hard to know if the new treatment caused the issue or if it was a pre-existing heart issue. Once a treatment is approved, researchers might do a "real world" study without those restrictions, to get a better idea of how the treatment will really affect all patients. Because all of the elements in this trial (Tafasitamab, Rituxan, and Revlimid) had already been approved, there was already plenty of "real world" data on side effects. So the trial could include a wide range of FL patients -- those who were asymptomatic, those with POD24, etc. So there is more certainty that the combination will be helpful for many patients.

Finally, Dr. Poh talks about the significance of this being a non-chemotherapy treatment. When R-squared was approved, it was a very big deal.  It was the first time a non-chemotherapy treatment was shown to be as effective as traditional chemo like R-CHOP or B-R. And now, this combination is perhaps even more effective than R-Squared. Because treatments like this are more targeted, affecting fewer non-cancer cells than chemotherapy, they have a different set of side effects. (One of the big takeaways from R-Squared being approved was just that -- different side effects, not necessarily fewer or less harsh side effects.) But the feeling is, according to Dr. Poh, that it will not result in long-term side effects like bone marrow damage that can come from chemo. So it may result in greater use by oncologists.

It will be interesting to see if that is true -- that this non-chemo treatment becomes a replacement for chemo, or if it becomes just another option for second and third line situations. I haven't seen too much of this kind of analysis, but it's speculation, anyway. "Real world" data will tell us for sure in the years to come.

Dr. Poh was on the team that conducted the trial, so she has seen the effects of the treatment in patients. If any of you has a conversation with your oncologist about this as a treatment option, please do share what you learned.

 

Does It Matter How You Were Diagnosed?

I have communicated with many patients with Follicular Lymphoma over the years, and read many more patients' stories. I'm always struck by how heterogeneous this disease is -- how differently it presents itself in different people.

I know I'm fortunate to have a version of this disease that started slow and has mostly remained that way. So many others I have spoken to have had a very different course for their disease.

One of the places where we have different experiences is in how we were diagnosed. Some of us had very obvious symptoms -- swollen nodes, night sweats, weight loss, for example. Others of us had no symptoms at all, and were diagnosed almost accidentally, maybe because a routine blood test turned up an issue, or an unrelated surgery or scan found some hidden swollen nodes. My experience is kind of in between -- I had a persistent swollen node near my hip, but I didn't have any other symptoms, and I was otherwise healthier than I had been in a long time.

Some of us might have asked a question related to this -- does it matter how I was diagnosed? Is an "accidental" diagnosis with no symptoms somehow better than a diagnosis that came because of some very obvious symptoms?

Some researchers from the Mayo Clinic had that same question, and published their results in the Blood Cancer Journal. The article is called "Incidental vs. symptomatic diagnosis of follicular lymphoma: implications of earlier detection." They essentially want to know if a patient is better off being diagnosed before there are obvious symptoms. The logic is that such a diagnosis must be early, and an early diagnosis must be better. 

The results are interesting, and depend on how you define "better." To me, as someone who has been reading about FL for a long time, they aren't really very surprising.

The researchers looked at the medical records of 908 patients who were newly diagnosed with FL between 2002 and 2015. They looked at how they were diagnosed -- because of obvious lymphoma symptoms, or "incidentally." They found that 259 (or 28,5% of their sample) had an incidental diagnosis. 

They looked at some of the characteristics of the two groups. The incidental group was more likely to be diagnosed with "early" disease -- stage I or II. This makes sense to me. They also found that this group had normal LDH levels. Most of you probably know what LDH (lactate dehydrogenase) is, or have at least heard of it. It's an enzyme found in tissues, and high LDH is often present when FL is advancing. I know it's one of those blood test components that my oncologists always point out ("LDH looks good."). So those in the "Incidental" group had normal LDH levels -- again, not surprising.  

Those are the differences. It's the similarities between the groups that are so interesting.

comparing the "incidental" and the "symptomatic" groups, there was no difference in Event Free Survival (EFS), Lymphoma-Specific Survival (LSS) or Overall Survival (OS).

In other words, whether the patients in the study were diagnosed early or later, they tended to go about the same amount of time before they needed treatment. There was no difference in how long they lived because of their lymphoma. In fact, there was no difference in how long they lived, period.

As I said, as someone who has been reading about FL for a very long time, this did not surprise me. It takes a lot to improve Overall Survival in Follicular Lymphoma. Watching and waiting versus immediate treatment? Not much difference in OS. Maintenance versus no maintenance? Not much difference in OS. Traditional chemotherapy versus nob-chemo treatment? Not much difference in OS.

And that matters.

It would be wonderful to have some breakthrough in FL that vastly improved our Overall Survival. In general, our OS has improved quite a bit since I was diagnoses 17 years ago. It was still unofficially 8-10 years back then. Now, it's closer to 15-20 years. No one knows for sure for a really great reason -- FL patients keep living so long that they can't measure the upper end of their survival. That's an excellent thing.

But all of this really matters most to me because it should ease our minds just a little.

The disease is heterogeneous -- we all experience it just a little bit differently. One implication of that is that there is no real "right answer" when it comes to treatment. If all FL was the same, we'd be able to say "start with treatment X. If you need treatment again, go with Y. And then Z." But we don't have that clear path. 

And that means lots of decisions to make, and lots of doubt that the decisions were the right ones.

Research like this should ease your mind. The decisions that you and your doctor make -- about when to start treatment, which treatment to try, and what to prioritize -- in the end, those decisions probably won't affect your survival. You don't need to say "Maybe I should have tried a different treatment" or, more to the point of this study, "Maybe I ignored that symptom too long and I would have been better off if I had been diagnosed earlier."

Forgive yourself. You made the right decision, no matter what it was. 

As I said, I'd love to see some research that tells us the right thing to do, with no doubts or questions.

But research like this is second best -- it tells us that whatever it was that we did, it was OK.

Take care, everyone.

Princess Catherine and Survivorship

Catherine, Princess of Wales, spoke a few days ago about her post-cancer life. It happened as she was visiting patients at a hospital. It seems like it was prompted by her dropping out of an event (the Royal Ascot, a horse racing event) that the Royal Family traditionally attends each year.

In the interview, she talked about the struggles she has had since finishing her cancer treatment. It is remarkable in the way she covers most of the issues that are related to survivorship.

I won't go through everything she said, but it amounts to this:

After successful treatment, everyone, including yourself, can think that everything is OK.  During treatment, she said, "you put on a sort of brave face." But when treatment is over, it can be "really difficult."

Part of the difficulty is physical -- your body is still recovering from the side effects of treatment. As she said, "You're not able to function normally at home as you perhaps once used to."

And part of the change is psychological. After treatment is over, "then it's like 'I can crack on, get back to normal'." But "the phase afterwards is really difficult, you're not necessarily under the clinical team any longer."And without that team that you were working with, there's some element of fear that comes with it. All of this lines up pretty much exactly with the recent survey results that I wrote about a few weeks ago.

One of the patients she talked with agreed: "It can be very discombobulating, in that time when you've finished active treatment."

I think all of this is a great reminder that survivorship isn't easy. As she said, "It's life-changing for anyone, through first diagnosis or post treatment and things like that, it is a life-changing experience both for the patient but also for the families as well....You have to find your new normal and that takes time... and it's a rollercoaster it's not one smooth plane, which you expect it to be. But the reality is it's not, you go through hard times."

And in a weird way, that should be comforting. If you're post-treatment and struggling, whether it's physical or emotional or spiritual -- you're not alone. I'm sure Catherine is getting the best treatment and post-treatment care possible, and she's struggling anyway. Cancer doesn't much care whether or not you have a crown on your head.

The lesson, of course, is to seek help if you feel like you need it. See if your cancer center has a survivorship program. If not, ask your oncologist of there are services available -- physical therapy, or a social worker or other mental health counselor, or a nutritionist, or something else (the Princess apparently found acupuncture very helpful).   

I appreciate Princess Catherine being willing to speak out about this. I remember when her diagnosis was first announced, there was little detail given, and I defended her right to keep things private. We all need to deal with our diagnosis and treatment in whatever way makes most sense to us and helps us. I would love it if every famous person was completely open about everything. But that's not their responsibility. They owe no one anything, except themselves and their loved ones.

So Catherine speaking out about survivorship is a wonderful thing. I hope it brings some comfort to a lot of patients and survivors.

Primary Extranodal Follicular Lymphoma

The journal Hematological Oncology just published an article called "Primary Extranodal Follicular Lymphoma: A Retrospective Survey of the International Extranodal Lymphoma Study Group (IELSG)." It actually doesn't affect most of us directly, but I think the bigger picture is probably important to us all.

The study described in the article looks at Primary Extranodal Follicular Lymphoma.

Extranodal FL means FL that exists outside the lymph nodes, and other organs related to the lymphatic system like the spleen and bone marrow. It's fairly common for FL to move out of the lymph nodes and into the spleen or bone marrow -- that's the very definition of stage 4 for FL, and about a quarter of FL patients are diagnosed with that stage. 

And if the lymphoma starts in the lymph nodes and then moves somewhere else, it's called secondary extranodal FL.

This article looks at primary extranodal FL -- it starts in some part of the body other than the lymph nodes.  

As I said, this doesn't apply to most of us, but I have communicated with a few readers over the last couple of years who have had their FL present in this way. Maybe some of you are still reading.

The research was conducted by the International Extranodal Lymphoma Study Group (IELSG), made up of Lymphoma experts who are specialists in these types of Lymphomas. Keep in mind that "Lymphoma" is a very broad term, and there are as many as 90 different types of Lymphoma, depending on who is doing the counting. About 30 of them are Extranodal types.

This research looked specifically at Primary Extranodal Follicular Lymphoma. This seems much less common than other types of Extranodal Lymphomas. I say "seems" because, as the authors note, extranodal FL "has not been extensively described." So they set out to find as much as they could by surveying specialists about cases that they had documented. They looked at "605 pathologically reviewed cases from 19 different countries" so they could compare the clinical features at diagnosis and their outcomes, and compare them to nodal FL.

What they found was that the two most common sites for Extranodal FL were the skin (334 of the 605 they looked at) and the gastrointestinal tract (72 of 605). More importantly, those two subsets were very different from nodal FL and had different Overall Survival patterns. After a median follow-up of 5.5 years, the cutaneous (skin) FL had an 89% 10 year OS, and the gastrointestinal FL had a median 10 year OS of 79%. For those gastrointestinal FL that presented in the duodenum (the first part of the small intestine), the OS was 95%. Other extranodal FL sites were similar to nodal FL. 

I think this is all good news for those of you with Primary Extranodal FL.

The bigger picture, though, is what interests me more. The researchers conclude by saying "These findings support the identification of specific primary FL localizations as distinct entities with particular clinical and biological characteristics." In other words, not all FLs are the same.

In some ways, that's really obvious. FL has a reputation for being heterogeneous -- it seems like we're all a little bit different. That was the conclusion of one of the ASCO presentations that I reviewed a couple of weeks ago. 

And yet, as obvious as it seems, we're still all kind of lumped in together as "Patients with Follicular Lymphoma." I think this goes back to not so many years ago, when diagnosis was done mostly by microscope. On the surface, all FL cells look very alike. As diagnostic tools, and our understanding of genetic features, becomes more sophisticated, it gets easier to see the differences. So some of us are probably still close enough to be a patient with FL, and to follow the same treatment recommendations as everyone else.

But that greater recognition that not every FL is the same will have significant implications in the future. We already know that, for example, grade 3B FL isn't really like other FLs. And POD24 FLs aren't really the same as others. But the more researchers can recognize specific features of different subtypes, the better off we will all be when it comes to diagnosis and treatment.

So that's my takeaway from all of this. It seems like very positive news for those of you for with Primary Extranodal FL. And for all of us, it's at least a small step toward making FL a little more manageable by identifying the things that make it heterogeneous. 

And those small steps are what move us forward.

 

Survivorship and Lymphoma

I've written a lot lately about the idea of "survivorship" -- what happens after treatment is over. It's an important issue for al cancer patients. Very often, health professionals are focused on making us better, and there isn't time or resources or expertise to deal with what happens after that. 

That's changing somewhat, and more and more cancer centers are focusing on survivorship, sometimes by having a dedicated office or clinic for patients who are no longer "patients," but who are still dealing with the physical and emotional effects of cancer, months or years later. That's certainly not the case for every cancer center, though.

I bring this up again because JCO Oncology Practice recently published an editorial on the topic, specifically on survivorship for Lymphoma patients.

I'll get to that, but first I want to look at the article that the editorial was responding to. It was aso published in JCOOP, in February. It's called "Perspectives of Lymphoma Survivors and Oncology Care Providers on Survivorship Care: A Qualitative Study." The article presents research based on in-depth interviews with 32 Lymphoma patients and 13 oncologists. This is what a "qualitative" study is, as opposed to a "quantitative" study. Rather than giving a survey to a large number of patients and presenting the results as numbers, it looks at a smaller number of patients and looks for themes and patterns in their words. (Both types of research can be valuable.)

The research found three main themes. I don't think any of them will surprise you. The first is that Lymphoma patients often have a "profound fear of recurrence" and anxiety after treatment is finished. Patients wanted more information about signs and symptoms that their cancer might return, and more reassurance from their cancer team. 

The second is had to do with which doctor to see after treatment was "finished." Some wanted to continue to see an oncologist. Some were forced to see a primary care physician instead. Others saw the value of seeing a PCP but had trouble finding one. It's a complicated issue, and one that came up during the Follicular Lymphoma Foundation webinar that I spoke at earlier this month.  

Finally, during the interviews, it became clear to the researchers that formal survivorship programs were necessary, and that they needed to include psychosocial support, wellness services, and assistance with financial and employment programs to help survivors transition to their different lives. 

That last sentence was a hard sentence to write -- I tried "go back to their old lives," but there's really no going back. Then I tried "their new lives" but that's not right either, because it kind of implies that everything is OK after treatment is over, and it's not. So I went with "different lives," which I'm also not satisfied with, but which is probably more accurate than "old" or "new." And that pretty much sums up why survivorship is such a complex topic, doesn't it?

And I also recognize that "survivorship" is different Follicular Lymphoma survivors. That first one, the fear of recurrence, might be worse for us. If you're like me, you've been told since diagnosis that it's incurable, and we can expect to to come back. So maybe it's better, not worse, since many of us just accept that recurrence is inevitable and we can prepare ourselves for it?

 Like I said -- it's a complex topic. And it affects each of us a little differently. 

Which brings us to the more recent piece from JCOOP, published a couple of weeks ago, in response to the qualitative research above. It's called "Bridging the Gap: The Essential Role of Lymphoma Clinicians in Guiding the Transition From Lymphoma Treatment to Survivorship." 

As the authors of this piece note, one of the big issues related to survivorship is the lack of information that Lymphoma patients receive about what their lives will be like after successful treatment. That's certainly a factor in the fear that patients feel in that first theme. And its a factor in the second one, too, in the confusion about seeing an oncologist vs seeing a PCP -- will a PCP know enough about Lymphoma to be useful? Ideally, the type of information that patients receive would be personalized, since each of us does deal with survivorship in our own way.

Given that JCOOP is a medical journal for oncologists that work with patients, the recommendations from the authors are aimed at Lymphoma clinicians -- the oncologists that work most directly with Lymphoma patients. But they have lessons for us as patients, too.

Their first bit of advice for oncologists is to Prepare -- to start conversations with patients early, and continue them over time. Since patients tend to be focused on the present, it helps to gradually and repeatedly introduce the idea of survivorship over time, to let it all sink in. They suggest the use of Survivorship Care Plans -- a written record of your treatment and symptoms, including emotional symptoms, and how you'd like your concerns to be addressed. That's an excellent idea for us as patients -- consider creating one even if your oncologist doesn't suggest one formally.

The second bit of advice is to Acknowledge and Assess -- for the oncologist to ask questions about emotional well-being and fears, and to recognize that they are valid. As patients, we can help here by bringing them up even if the oncologist does not. I think it's also important to be prepared to have an oncologist that may dismiss them ("You have nothing to be worried about") or downplay them, or just not know how to deal with them. I like to think that someone in oncology would be well-aware of patients' fears, but I know that isn't always the case. Be open about it anyway. If nothing else, it will be a good education for the oncologist.

The third piece of advice for oncologists is Connect -- to be aware of survivorship services and help patients make contact with them. Again, as patients, we can ask questions about these kinds of services. They are often available, even if some oncologists don't know that. Pushing for information might make a less-informed oncologist seek out the information. And a well-informed oncologist will be able to pass on that information to you.

Finally, the last bit of advice for oncologists is to Evaluate and Document -- to ask patients how they are doing and make sure that their emotional well-being becomes a part of the permanent record. Again, we can help as patients by making sure that we bring up the subject ourselves. And it's not just emotional issues or concerns -- we should bring up physical issues, financial issues, anything that cancer has done to make our lives different.

As you can tell, I think the message to oncologists is interesting, but more importantly, I think the JCOOP piece provides an opportunity for us as patients. Some of us might be fortunate enough to be affiliated with a cancer center that has a survivorship program, and to have an oncologist that knows about it and intervenes early. Or maybe the opposite is true -- no program and an oncologist that isn't aware of the issues. Or maybe something in between.

Whatever the case, I think it's important for us as patients to be proactive. We need to be aware of our own needs, and unafraid to bring them up. If enough of us do so, it becomes a regular and expected part of our conversations with our doctors. That's good for all of us.

Stay well, and stay proactive.

FDA approval for Tafasitamab-cxix for R/R FL

The FDA has approved Tafasitamab-cxix (also known as Monjuvi) in combination with Lenalidomide (also known as Revlimid) and Rituxan for Relapsed/Refractory Follicular Lymphoma.

I wrote about this combination in November, just before the ASH conference. The results of a phase III clinical trial were being presented at ASH, and the website Fierce Pharma called the early results a "triumph." The makers of Tafasitamab had said immediately afterwards that they were going to seek FDA approval. And it came.

Tafasitamab had already been approved by both the FDA and the EU for use on R/R Diffuse Large B Cell Lymphoma, in combination with Lenalidomide.

Tafasitamab is a monoclonal antibody, like Rituxan. But Tafasitamab targets a different protein, CD19, on the surface of B cells (Rituxan targets CD20). The idea was that combining the two (along with Lenalidomide) would increase the chances that the treatment could find the cancer cells. That seems to have been the case.

The trial involved a direct comparison between Tafasitamab + Lenalidomide + Rituxan and a placebo + Lenalidomide + Rituxan. In other words, patients in the trial were going to receive either this new combination or just R-squared (Lenalidomide/Revlimid + Rituxan). Patients in the trial had already received at least one treatment for their FL already.

As Fierce Pharma said, the results were triumphant. After a median follow up of 14.1 months, the Progression Free Survival for the Tafasitamab combination was 22.4 months and 13.9 months in the other group. The Complete Response Rate was 49.9% for Tafasitamab and 39.8% for the other group, and the Overall Response Rate was 83.5% vs 72.4%.

The question with the combination was going to be about safety. Monoclonal antibodies like Tafasitamab and Rituxan work by eliminating B Lymphocytes, a kind of immune cell. They target both healthy B cells and cancerous B cells. So while having two antibodies targeting the same cells might mean it's more effective, it also means you're running the risk f having too many immune cells being disabled all at once, opening up the possibility of greater risk of infections.

And that did happen. In their announcement, the FDA points out that "serious adverse reactions occurred in 33% of patients" in the Tafasitamab group, including serious infections in 24% of participants.The announcement doesn't give a direct comparison to the other group in the trial, though the ASH presentation did -- 36% of the Tafasitamab group vs 32% for the other group (the FDA numbers are a little different because they were updated 6 months later). Also in the ASH presentation, it was noted that during the study, 15 patients in the Tafasitamab group died, 5 because of disease progression and 6 because of side effects, versus 23 in the other group (17 due to disease progression and 6 from side effects). 

It will be interesting to see how popular this combination becomes with oncologists. Will this become a substitute for R-Squared? Similar way of working, but more effective? Or will some patients still be given R-squared instead because it seems slightly less aggressive on the immune system? (Remember, I'm not a medical doctor -- these are just questions that are coming to me immediately after reading this). I look forward to reading more commentaries in the coming weeks and months.

ASCO: Exercise and Cancer

A reader left a comment on my last post that I want to address here, rather than in the comment section:

Thank you for ASCO coverage. Seems ASCO's headline grabber this year was the "Structured Exercise Program Improves Survival Outcomes in Patients With Stage III or High-Risk Stage II Colon Cancer" story. Do you think this study translates to FL folks, especially in terms of recurrence and survival? I just noticed current Mayo study along the same lines for indolent NHL lymphomas CLL and MZL. Any "there" there?

I have been reading about this presentation, and I was considering writing about it (especially since there is so little to write about Follicular Lymphoma this year. 

My quick take on it is this -- it's a study that describes a very specific research project, and was reported with some headlines that make it seem to affect many more people than it actually does. It is both excellent research and a good lesson in reading carefully.

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

Let me start off with one of the headlines that describe this study (from NBCNews.com, which shouldn't be so clickbaity): "Exercise may benefit colon cancer patients as much as some drugs."

Now, clickbait is a headline that is meant to get you to click on it and visit the page. If I'm being fair, the title I'm using for this blog post is kind of clickbaity, but that's the point -- the title doesn't fully represent what the content of the article says, exactly. There were a lot of articles that did something similar, speaking in very general terms about the study to make it more attractive to readers. It's a very common tactic in popular science writing. The NBC News headline makes it sound like exercise is a substitute for more traditional cancer treatments for anyone with colon cancer.

That's not the case. Exercise didn't cure anyone's cancer.

But that's not to say it isn't an important study. From what I read, when the presentation was finished, the oncologists in attendance actually gave a standing ovation. So what the study actually says is still pretty important.

The presentation is #LBA3510 "A randomized phase III trial of the impact of a structured exercise program on disease-free survival (DFS) in stage 3 or high-risk stage 2 colon cancer: Canadian Cancer Trials Group (CCTG) CO.21 (CHALLENGE)."

The study looked at 889 patients with colon cancer from Canada and Australia, median age 61. About 90% of the patients had stage III colon cancer, and the other 10% had high risk stage II. The patients all had surgery followed by adjuvant chemotherapy (that is, chemo that was meant to "clean up" any remaining cancer).

It's worth repeating this, given the headlines -- all of the patients had surgery and chemotherapy. Traditional cancer treatments played a huge role in making them cancer-free. Exercise did not cure or prevent their cancer, at least in this particular study.

After chemotherapy, patients were split into two groups. The first group was given Health Education Materials (the abstract calls this the HEM group) that promoted good nutrition and exercise. The second group was given a Structured Exercise Program (they are the SEP group), supervised by a Physical Activity Consultant, who met with them twice each month for three years. The specific physical activity was chosen by the SEP patient. It could have been working out in a gym or it could have been just walking for 45 minutes per day. But it was structured, supervised, and done regularly. 

The results were fascinating. With a median follow-up of almost 8 years, 93 patients in the SEP group had their cancer come back, compared to 131 in the HEM group. After 5 years, the disease-free survival (DFS) was 80% for the SEP patients and 74% for the HEM patients. The 8 year Overall Survival was 90% for SEP and 83% for HEM.

This was a fairly large stage 3 clinical trial, not just observations or reports from patients, and that's what makes it so impressive. The patients in the trial reported in with their consultant every two weeks for 3 years. All of this is enough to make it pretty clear that the difference in the two groups with the physical activity that one group performed. Exercise didn't cure anyone's cancer, but it might have helped keep 90% of the patients alive for 8 years.

Now, I want to be clear about something else -- the reader who left the comment wasn't implying that exercise alone was a replacement for conventional treatment. The reader is clearly reading carefully, even referencing another Mayo Clinic trial on blood cancer. That reader is being careful.

That said, I don't know the answer to their question, Do you think this study translates to FL folks, especially in terms of recurrence and survival? I just noticed current Mayo study along the same lines for indolent NHL lymphomas CLL and MZL. Any "there" there?

This is a good time to once again remind everyone that I am not a medical doctor, and the best person to ask about treatment and lifestyle choices is your own oncologist. 

But I will say, for what it's worth, as a non-expert, I think exercise is an excellent idea, whether you are watching and waiting, in active treatment, or post-treatment. Moving our bodies is always a good thing. 

One of the great details from this study is the range of exercise that the participants engaged in, and the fact that it was their choice. I've heard it said that the best exercise that you can do is the one that you enjoy enough to keep on doing it. Sometimes when we think of a "structured exercise program,"  we imagine going to a gym and having a trainer yell at us as we push large amounts of weight. If that's what you enjoy, keep doing it. But if a 2 mile walk every morning is your thing (as it is with my wife and me), then keep that up. And if you have physical issues that make that harder, then find something else -- a shorter walk, or chair yoga, or water aerobics. But keep moving.

The best part of all of this was the enthusiastic reaction of the oncologists in attendance. I hope this means there will be follow-ups -- more rigorous studies on the benefits of exercise, whether it's post-treatment or during treatment. 

So I certainly hope there is some "there" there. We'll know for sure when the results of the Mayo trial get presented or published.

In the meantime, I encourage you to do two things:

1) Read carefully.

2) Keep moving.

More soon.