Moving Toward a Chemo-Free Future

I'm going to give you a short, easy post today because I've been using my bad arm too much this week and it hurts. I'm scheduled for surgery in a couple of weeks, and I'm trying to get as much done as I can while I still have use of both arms.

So I found a nice article called "Follicular Lymphoma: Moving Toward a Chemotherapy-Free Future," which appears on SurvivorNet and features the opinions of Dr. George (Changchun) Deng of UH Seidman Cancer Center in Ohio.

This isn't about new research. It's a kind of summary of where we are right now in terms of treatment options. If you've been reading for a while, you know I like to post this kind of article every now and then. It's nice to stop and sum things up every now and then.

Dr. Deng's main idea is that we are moving away from chemotherapy as the main treatment in Follicular Lymphoma, and moving more towards treatments that use the immune system to treat the disease. Traditional chemo can affect healthy cells as well as cancer cells. Newer treatments target cancer cells more directly. Here's a very hopeful line from the article:

"The exciting question is no longer simply whether we can control follicular lymphoma, but which immune-based treatment is best for a particular patient and when it should be used."

Among the treatments that are discussed in the article are Tafasitamab, bispecifics like Epcoritamab and Mosunetuzumab, and CAR-T. 

At the same time, chemotherapy is still around, and still an option. Just a few months ago, research suggested that R-CHOP could cure FL for many people. And chemo options are still preferred by many oncologists for transformed FL.

It's a very hopeful article, and very easy to read (SurvivorNet is aimed at patients). 

I'll rest my arm and try to right more about some newer research in a few days.  Maybe I'll do videos instead (I've got a face that was made for Tik Tok, I think.)

More soon. Stay well.

 

 

Good News for Bispecific Mosunetuzumab

The maker of Mosunetuzumab, the bispecific, released news this week that their phase III clinical trial for Mosunetuzumab and Lenalidomide seems to be an improvement over R-Squared. I think I have received about 20 different notifications from Google Alerts about it. That's a decent indication that this is a big deal.

As you probably know, Mosunetuzumab is the first bispecific to be approved for treating Follicular Lymphoma. Bispecifics work because they have two parts. One targets a protein on the surface of the cancer cell (CD20) and the other targets a protein on an immune cell (CD3). By attaching to both, it brings the immune cell next to the cancer cell and allows the immune cell to eliminate it. 

The phase III clinical trial is called CELESTIMO. It's a two-arm randomized study, meaning the 400 or so patients in the trial are randomly given one of two treatments. So ne group received Mosunetuzumab + Lenalidomide, and the other received R-Squared (Rituxan + Lenalidomide, also known as Revlimid, which gives you the two Rs).

[I want to make a prediction here. Mosunetuzumab is also known as Lunsumio. This combination is going to end up being known as L-squared -- Lunsumio + Lenalidomide. If you're comparing it to R-Squared, this just seems inevitable. I'm all for it. I just wish this blogging program did a better job with superscripts so I wouldn't have to type out :Squared" all the time.]

The results of the CELESTIMO trial are very positive. The manufacturer says the Mosunetuzumab combination resulted in a higher PFS (Progression Free Survival) than the R-Squared, meaning it took longer for patients' disease to become get worse. The manufacturer also said there were no new side effects from combination, only those that were already known about from Mosunetuzumab and Lenalidomide separately.

The manufacturer didn't release any data to back all of this up. They said they will do that either at an upcoming medical conference or in a publication.

[Prediction #2: They'll release the results at ASH and it's going to be one of the major sessions, big enough to be held in the ballroom of the hotel. And then it will be published in the journal Blood just a few days later.]

It's a big deal, given R-Squared's history. The combination was approved in the U.S. in 2019, and it was seen as a major step forward. It was the first non-chemotherapy treatment that was shown to be as effective as traditional chemotherapy like R-CHOP or Bendamustine. Chemotherapy still has a place in FL treatment, but newer treatments are more targeted, doing less damage to healthy cells. (To be clear -- one big takeaway when R-Squared was approved was that it had different side effects than chemotherapy. Not better or worse, but different.)

So if a second non-chemotherapy treatment exists that better than both chemo and R-Squared, then that's a very big deal. We won't really know just how big a deal until the manufacturer releases the data that shows us how effective and how safe it really is.

It's also a big deal given all of the excitement that we saw over the summer from the EHA conference over a presentation on Epcoritamab and R-Squared. Epcoritamab is the second bispecific to be approved for FL, and it has been used in combination with several other treatments in different trials. I suspect the manufacturer of Mosunetuzumab released this news without any data because they wanted to remind people that Mosunetuzumab is still around and there is plenty to be excited about for their bispecific as well.

I'll keep an eye on this one. I'm pretty confident we'll get the data at ASH in a few months (though I'm also notoriously not good at predicting things.) 

More soon. I have to get a few more posts in while I can still use both arms. 

Seasonal Patterns of Cancer Diagnosis

Well, this post isn't about Follicular Lymphoma, but it's certainly about cancer. And not too complex. And with my bad shoulder, I'm trying to stay in the habit of writing, and "not too complex" is good for that. 

I saw an article this weekend called "Seasonal Patterns and Implications of Cancer Diagnosis Across Calendar Months," published in in JAMA Network Open. 

The objective of the research is pretty straightforward -- is there a month of the year that has more patients in the United States diagnosed with cancer than other months? And if so, why?

The answer is, yes, there is a month with more cancer diagnoses. It's January. This is, of course, the month when I was diagnosed.

The researchers looked at data from cancer registrations and found 30,184,124 cancer diagnoses between 2001 and 2019. (Hey, I was in there!)

They found that January was highest, with 8.81% of cancer diagnoses. Here's the full list:

January 8.81%

February 7.78%

March 8.51%

April 8.35%

May 8.44%

June 8.60%

July 8.17%

August 8.46%

September 7.98%

October 8.58%

November 7.85%

December 7.76% 

There isn't a huge difference between months, but enough to matter. There's a 1% difference between December and January, which is about 300,000 cancer diagnoses. And it's important to keep in mind that these numbers aren't about when people get cancer -- that is, when the disease begins -- but about when they are diagnosed -- when a doctor confirmed that they had it. That's important.

The other question is, why does this pattern exist?

The researchers can't say for sure, but a fairly simple explanation could be that there is lower clinical activity in December and higher in January because of the holidays. In the U.S., "the holidays" starts in late November with Thanksgiving and goes through January 1 with New Year's Day.  People are focused on parties, shopping, spending time with family. It's too happy a time to think about whatever symptoms might be showing up. 

It's also possible that "workforce and specialist availability" has an impact diagnostic timing. It's harder to get an appointment at some parts of the year. 

There are also insurance-related factors. In the U.S., we don't have a public insurance system like in Canada or the UK. It's a complicated system, where something like a "deductible" has an impact. That is, depending on the deductible level, a patient will have to pay for much of their care on their own before health insurance begins to pay. So diagnoses might come later in the year after a deductible level has been reached and some patients can finally afford it. 

And then there are things like awareness campaigns. October has a high number of diagnoses, partly because of an increase in breast cancer diagnoses. October, of course, is breast cancer awareness month. Summer sees a rise in some diagnoses of skin cancers like melanoma. Many people become more aware of skin cancer in the summer months, when they are wearing less clothing and spending more time in the sun.

For me, it seems like it was just coincidence, rather than some seasonal-related issue. I was dealing with health problems starting in June, and it was late November that I went to see a surgeon about the large lymph node near my hip. After some antibiotics didn't work, we scheduled a surgical biopsy, and the results didn't come through until January. I wasn't putting off my health because of the holidays. 

But I think the research makes an important point -- sometimes it's an outside factor that pushes us to take care of our health. It's an easy thing to put off, and I have had loved ones who waited too long to get a diagnosis because they were afraid of what they might find out. Their outcomes were not good, and I lost them much sooner than I wished.

So sometimes we should be the outside force. Not a holiday or an awareness campaign. Just a concerned individual who cares enough about someone to encourage them to see a doctor. 

I'll get back to the FL research soon. But this gives us some things to think about.  

 

 

 

 

I'm Kind of a Mess

I know it's been a week since I posted anything here. I've been dealing with some stuff.

I had an MRI this afternoon. Shoulder injury.

Last Thursday, after I finished my blog post, I went to a dog training class with my standard schnauzer. There was someone there with a 100 lb. German Shepherd, and the big dog really did not like my little dog. The big dog's owner commented on it a few times, how his dog really likes most dogs, but just doesn't like certain dogs, and mine seemed to be a one of them.

Which would be fine, except this dog owner also gets distracted easily, and at one point, his big dog broke away from him and ran at me and my little dog. (Don't worry! No dogs were harmed!). I moved to my left to put myself between the two dogs, but my dog moved to the right, pulling on the leash and twisting my arm. The big dog decided it didn't want any trouble after all and his owner eventually came and puled him away.

So I've been hurting for the last week or so. Everything is taking more time than I'd like it to. 

When I went to see the orthopedist a few days ago, he moved my arm around a lot, and had me try to move it on my own, and had me try to push against his arm in different ways, and mostly reacted to all of these things by saying, "Oh, that's not good." 

He suspects a bad tear of my rotator cuff, which is kind of what I figured, too (though I was hoping I'd lucky and it would just be a bad sprain).  I actually had a torn rotator cuff in my opposite shoulder about 12 years ago, so I know what to expect from here. Whether that's good or bad, I don't know. But there will be surgery, and weeks of recovery, and months of rehabilitation, if history is a guide. 

So, yeah, I'm kind of a mess. I'm looking back at the last year, and I'm not happy about it. I was in physical therapy for months because of a knee injury.  I hurt my back a few weeks ago and had to take a break from yoga. There's the whole MGUS thing. 

I remember reading a couple of years ago that our bodies go through large changes in our 40s and 60s. (I found the article! It's our mid-40s and early 60s.) So I'm ahead of the curve on both of those ages, with cancer at 40 and a bunch of other stuff before 60. My mom always told me I was very advanced, so there you have it. 

Before I finish, a little reflection on the MRI that I had today. It's been 12 years since I had one, and I really don't usually mind any kind of testing. I mean I don't look forward to the results, but I'm fine with scans or biopsies or shots or blood draws or whatever. But I was kind of anxious about this one for some reason. In the phone call to set up the appointment, and then in two online surgeries, I kept being asked about being claustrophobic. If you're not familiar with an MRI, you get fed into a small tube, so it's a very enclosed space. I remember 12 years ago being very squished in, so my injured shoulder had to be in an unnatural position, which was very painful, and I had to hold still for 30-45 minutes. It was not fun.

But this one was different. There was much more room in the tube -- I could lie flat -- and the whole process took less than 15 minutes. It was still awful, but not as bad as I had anticipated. 

I think about the advances in cancer treatment that have happened since then, too. It doesn't seem like it, but 12 years is a long time.  A whole lot has happened in the world of Follicular Lymphoma in that time.

As we were driving home, my wife said maybe there have been some shoulder surgery advances n that time, too, and I'll do some quicker healing. That would be wonderful. I will hold out hope.

Because hope is a good thing, maybe the best of things.  (Quoting Shawshank Redemption always makes me feel better.)

I'll keep you updated. And I'll try my best to get back to writing about Lymphoma research soon.

Take care.

 

 

Happy Lymphoma Awareness Month

If you're reading this blog, you're probably aware that this is Lymphoma Awareness Month. It's a good thing -- it's an opportunity for others to learn more about our disease. Lots of organizations are using the opportunity to do just that. If you follow the Follicular Lymphoma Foundation on social media, for example, you've seen their posts so far this month, highlighting symptoms in one, and questions that people have at diagnosis in another. Be sure to like them when you see them.They are good ways to have those posts show up on the feeds of your friends, followers, and connections. It's an easy way to spread awareness.

Almost every year, I make the comment that I really don't need an awareness month. I've been very aware of my Lymphoma for almost 19 years now. 

But it's a funny thing -- sometimes we're made aware of things whether we like it or not. 

Yesterday, I got a text and an email that there was a new letter in my Electronic Medical Records account. My first reaction was slight panic -- "Now what?" I asked myself.

I haven't had any appointments or tests or anything else in a couple of months.  What could one of my many healthcare providers need to tell me?

And what's up with it being a letter? I get the occasional message or result or note. But a letter? Is this 1857?

It turned to to be the very long set of notes from a genetic counselor that I spoke with a few weeks ago. I had put it out of my head.

If you aren't aware of this, a genetic counselor is a healthcare professional that provides advice about getting a genetic test to see if your DNA carries one or more genes that can cause certain cancers. The BACA gene is an example -- it can increase the risk of breast cancer. I have a family history of certain cancers that might have a genetic disposition. (Follicular Lymphoma is not one of them, as far as researchers know.)  If I choose, I can have a test that looks for those particular genes. And if it turns out that I have one, I can do things like be tested more earlier or more frequently, or in some cases, have surgery to remove non-vital organs that might be more prone to cancer.

As I said, I had the initial meeting with a counselor and then put it out of my head. I really don't know if I want to do it.

For one thing, I'm already so hyper aware of my own cancer history that I'm not sure it's necessary. I had a benign polyp on my last colonoscopy, so I'm getting tested in 7 years instead of 10. I see my oncologist twice a year. I see my skin doctor twice a year. I know every lump and bump on my body. I know when something doesn't feel right.

So it is the awareness worth it? I don't know.

Of course, the other reason to do this is because we pass on our genes to our children. Is it fair to them to not let them know if they carry a gene that increases risk? (There is never a guarantee that someone with a certain gene will get cancer.) Is it more fair to not tell them, so they don't have to live with the worry that I have experienced for 18 years, wondering if every lump and bum is cancerous? 

If I pass on my awareness, is that enough? Will they be vigilant enough to take care of themselves, knowing what I have been through?

I still don't know what I'll do about the genetic counseling. 

But I do know that awareness is a good thing. And it's worth celebrating the knowledge that there are tests available that can help us assess our risk. The questionnaire I filled out, and  the counselor, both asked if my relatives had been given genetic tests. Of course someone like my grandmother, who was born in 1907 and died in 1986, never had a genetic test. They weren't available.

And that's my point. We're living in a good time. Awareness is about hope. More knowledge might mean an earlier diagnosis and a life saved.

I hope you find something to celebrate this month. Treat yourself well. You deserve it.

 

Protecting the Heart During Chemotherapy

The JAMA Network Open published a research letter last week that I thought was very interesting. It's called "Primary Cardioprotection in Frontline Anthracycline Therapy for Adult Hematologic Cancers," and it brings up some important issues that get at the heart of where we are these days with Follicular Lymphoma treatments.

(There's a really funny pun in there that you'll get if you re-read this post.)

The research letter looks at some research on Anthracyclines, a class of traditional chemotherapy drugs.  They are very powerful. The "H" in "R-CHOP," a common chemotherapy for FL, stands for Hydroxydaunorubicin, which is also known as Doxorubicin or Adriamycin. This is the Anthracycline in the combination. It works by messing with the cancer cell's DNA so it can't grow and divide. 

But the big problem with traditional chemotherapy is that it can often do as much damage to healthy cells as it can to  cancer cells. And in the case of Anthracyclines, one of the places it can do damage is to the heart. This is why FL patients only get R-CHOP once, even if it was very effective. There is too much risk of heart damage over a certain dose, and it can take months or ears to show up.

The research here points out that there are ways to help minimize the heart damage that Anthracyclines can cause. First, patients can be given a drug called Dexrazoxane just before they receive the chemotherapy. This drug latches on to the byproducts of the Anthracycline to keep them from damaging heart cells. The other strategy is to use Liposomal Anthracycline Formulations. For this, the Anthracycline molecules are coated in lipids or fats that keep them from affecting heart tissue and lessening damage.

The researchers found that Anthracyclines are used in chemotherapy treatments for several different blood cancers, including FL. But these two strategies for cardioprotection (protecting the heart) are very rarely used.

They looked at medical records for blood cancer patients over 10 years (from 2014 to 2024) and identified patients who had received Anthracycline-based chemotherapy as a first treatment. They looked particualrl at patients who were diagnosed with Acute Myeloid Leukemia, Diffuse Large B-Cell  Lymphoma, Mantle Cell Lymphoma, and Follicular Lymphoma. They decided to focus their analysis to AML and DLBLC, because there were so few cases of cardioprotection for the MCL and FL patients.

(That's a huge problem that we'll get back to in a second.)

They looked at a total of 13,331 patients, including 3661 with AML, 7241 with DLBCL, 1154 with MCL, and 1275 with FL. There was "infrequent" use of cardioprotection -- only 2.4% of patients with AML and 1.1% of patients with DLBCL received either Liposomal Formulations or Dexrazoxane. As I said, the number of patients with FL who received cardioprotecion was too low to include (obviously, less that 1%).

The researchers are calling for more research into the use of cardioprotective strategies for blood cancer patients who receive Anthracycline-based chemotherapy, hopefully leading to greater use if the research justifies it.

I think there are a couple of important points that this brings up for us as FL patients.

First, this strikes me as a survivorship issue. As I have said many times, the idea of survivorship is becoming more and more important to me -- the idea that there isn't enough attention paid to what happens to patients after the treatment is over and we are told we are OK. I think "side effects" are often studied most intently for a fairly short period right after treatment. It's hard to measure long-term side effects. There are so many other reasons that an FL patient might have heart issues 10 years after treatment. But if Anthracycline-related issues might not show up for years, that doesn't mean there isn't a risk. I am fully in favor of research that tests out strategies for cardioprotection.

This is also an excellent reminder that side effects (long- and short-term) should get a thorough discussion when it comes time to decide on a treatment.As I have said before, even when I'm having a good visit with normal blood test results, I still like to bring up treatment possibilities. I'd rather have those conversations before they become necessary, rather than when I'm in a panic about choosing a treatment that needs to happen soon. It's a lot easier to have a thorough conversation then.

And this specific conversation matters. If you've been reading for a few months, you probably remember the research from last March on 15-year follow-ups of R-CHOP patients, and the possibility that R-CHOP had cured many of them.  I have no idea how this has been accepted by oncologists in the last 6 months -- if they are recommending R-CHOP to more patients. But if that's the case, then we need to do much better than 1% of FL patients receiving cardioprotection. This needs to be a part of the conversation if R-CHOP is back on the scene.

One other important point to remember -- no cancer treatment is without side effects. When R-squared was first declared an alternative to traditional chemotherapy, researchers were very clear that R-squared had side effects, and they weren't better than those from chemo, they were different. It's just not possible to fight something like cancer without causing other issues. The question is, how are those issues dealt with? What can researchers learn from some patients to better protect other patients? 

As I said, I think this kind of gets at the heart of where we are with FL treatments. There is, unfortunately, no single best way to treat FL. For all of the excitement about CAR-T and bispecifics and other immunotherapies, traditional chemo still has a place in FL treatment. And there's still lots to know. 

Do your best to keep up -- enough to be able to have a good conversation with your doctor when the time comes.

 

R-Squared: A Systematic Review

The Blood Cancer Journal just published an article called "Lenalidomide and Rituximab for Relapsed/Refractory Follicular Lymphoma: A Systematic Review and Meta-Analysis." 

We're at a point now where R-squared (Lenalidomide/Revlimid + Rituxan) is pretty firmly a part of our lives as Follicular Lymphoma patients. It's a standard treatment, the first option approved that showed to be as effective as traditional chemotherapy (but with a different set of side effects). It has been with us for about 7 years now as an approved treatment.

So this article is a "systemic review" of what we know about R-squared. It looks at all of the research that has been done since 2015, when the first stage 2 clinical trial results were published, on R-squared in Relapsed/Refractory FL. The aim here is to see if all of the results show the same thing, especially when compared to the AUGMENT trial that led to the approval. 

The authors wanted to look at as wide a pool as possible, so in addition to looking at just R-squared, they also looked at Lenalidomide + Obinutuzumab, which like Rituxan is an anti-CD20 monoclonal antibody. They also looked at triplets -- R-squared + some other lymphoma treatment. Finally, they looked at not just published research, but also at research that was presented at ASH, the largest hematology conference in the U.S., and EHA, the largest conference in Europe. 

Looking at so many sources of data is great, in that it gives them much more to work with. But it also complicates things. Each study had its own criteria for inclusion, so the patients across the studies don't match up with each other exactly. Some studies, especially those from the conferences, did not include all of the data that the published studies did. And some studies used slightly different dosing, so patients didn't get the same amount of the treatment across all of the studies.

All that said, they were able to do some analysis that made it possible to compare the different studies.

The results of their analysis aren't surprising -- R-squared works.

The Overall Response Rate for all of the R-squared or Lenalidomide + Obinutuzumab studies was 75.9%, and the Complete Response Rate was 39.6%. For studies involving a triplet (R-squared + another lymphoma treatment), the ORR was 85.1% and the CRR was 53.9%. This makes sense -- a third treatment will, in theory, add another way for the cancer cells to be treated. But something else happened, too, that also makes sense -- the rates of serious side effects went up, too.

In case you are curious about what the third treatment was in those triplets, they were Idelalisib; Polatuzumab; Atezolizumab; Bendamustine; ViPOR [a combination of 5 treatments, not three -- Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid]; Tazemetostat; Acalabrutinib; Epcoritamab; Azacitidine; and Tafasitamab. Some of those names are probably familiar to you, and I have written about a bunch of these trials over the years. You can search for them at the top of the page.

The analysis also broke down the data in a few other ways, including prior lines of therapy. They wanted to see if R-squared was more or less effective if someone had already tried a number of other treatments. If a treatment works when others don't, that's an important piece of data.  In studies where patients had received a median of just one prior treatment, the ORR was 76.7% and the CRR was 41.9%. For patients who had received a median of two or more prior treatments, the ORR was 73.5% and the CRR was 40.5%. There was no significant difference between the two -- R-squared works well no matter how many prior treatments a patient had received. The same was true for the triplets.

As for safety, as mentioned above, there were greater numbers of serious side effects for the triplets. Serious low white blood cell counts occurred in 46.6% of triplet patients, and just 29.1% of R-squared patients. There was a trend toward serious respiratory infections in the triplet patients vs. the R=Squared patients. Low platelet counts were similar in the two groups. Patients who had to leave the study because of serious side effects were also similar -- 23.3% in the triplet group and 16.6% on the R-squared group. 

There are other data breakdowns that you can read about in the article. Click the link. 

Overall, the analysis shows the effectiveness of R-squared and begins to look at some of the effectiveness of triplets, though they are generally more recent and will need more time to see long-term results. If you've been reading for a while, you now I like those "Here's where we are" articles and videos where an expert gives us an update on things that have happened in the past. I see this as one of those articles. It's clear the R-squared is effective and safe for Refractory and Relapsed patients and provides and important option for those of us in that situation. 

Photographs and Memories

I have an old phone. It doesn't have a huge amount of storage on it, so it fills up fast, to the point where I can't do any updates because there isn't any space.

I know the reason. I run my dog's Instagram page (oh yes -- that guy named Lympho Bob is not my only online persona).  I take several pictures of the dog every day. "For online content," I say to my wife and kids who roll their eyes at me when I tell them to keep still so the dog will stay in whatever cute position she is in. I end up with way more photos and videos on my phone than I actually need. And then I forget to go back and erase them and they pile up.

So over the last few weeks, I've been going through the photos on my phone, erasing anything that I don't really need, like duplicate photos of the dog or old memes that I though were funny and may r may not think the same now. Last week, my wife and youngest kid and I took a train ride into New York City to go to the Metropolitan Museum of Art. It's an amazing place. I spent the 2 hour train ride going through all of my photos for 2023. I had a ridiculous number of photos of my dog sleeping while she's lying on her back. Maybe two of them ended up on Instagram. It was very therapeutic to erase so many of them and create some space.

As you might imagine, going through thousands of photos brings back some memories. And some of those memories are directly related to being a cancer patient.

I found several photos that I had saved over several months, all variations of the same meme: "My Lymph Nodes are Assholes." I liked that one a lot, enough to save it whenever it came up. I don't think I ever re-posted it anywhere, including in this blog. But I enjoyed the fact that it kept coming back to me, and I kept enjoying it. And it's true -- if my Lymph Nodes were people, I probably wouldn't want to spend much time with them. They're much too negative. I'm getting to an age where I'm more selective about who I spend time with. I'd rather not have what they are offering.

I found another meme, a list written by a cervical cancer patient: "You Know You Have Cancer If...." and then there were 10 items like "You can pronounce difficult drug names correctly" and "You speak very freely about your own body." They were all very true. But my favorite was "You have a favorite vein." Because I do have a favorite vein -- left arm, along the inside of the elbow. It's a beautiful one -- I have been told so by many phlebotomists. In fact, when I get blood taken and the phlebotomist doesn't comment on how nice it is, I get a little insulted. "Pretty privilege," I think it's called. Those of us with beautiful veins can get a little bit obnoxious about it. 

I found a bunch of vacation photos of people I have met who are cancer survivors. My wife and I are doing our best to travel now, when we can, when we are healthy enough to enjoy it. We don't want to look back 10 years from now, wishing we had taken the trips we used to dream about. We're living the dreams now, as much as we can.

There were some photos of a group we had met on a river cruise, and one of the women in the group was a two-time breast cancer survivor. One night, when the wine was flowing at dinner, we started talking about how ridiculous it was to be diagnosed with cancer at a relatively young age -- me at 40, she in her late 30s. We were laughing in a way that cancer patients do sometime. But it wasn't a happy conversation for her husband. He said to me, stone-faced, "But it wasn't funny when it happened, was it?" No, it wasn't. I told him about watching moving with my young kids and turning out the lights in the room so they wouldn't see me crying. 

It's funny how shared sadness can make someone feel happier. 

A few years before that, we traveled to Italy, something we'd talked about for 30 years. While we were there, we met someone who was in active treatment for lung cancer. She and her husband were great travel companions, and we spent a wonderful afternoon with them in Venice -- one of our favorite travel memories in many years of traveling. Of course, it came out that both of us were in different stages of our dealing with cancer. She was a cancer blogger and writing teacher, like me. We had lots to talk about.

I kept up with her blog for a long time. As I said, she was in active treatment when we met. She is a long-distance bike rider, and enjoyed good days when she could get out and ride. She hasn't written anything on her blog since April. It was good news at that point -- she was able to see her oncologist three times a year instead of four. So I'm going to assume she's doing well and spending her time riding instead of writing. Writing about cancer is hard to keep up sometimes, I know. We all need a break. 

We had corresponded by email for a while, and that made me think of all of the emails I have received over the years from readers. I think about you all a lot. It's true. I'll read or something that will make one of you pop into my head. The filmmaker from the Netherlands. The doctor who retired and moved to Portugal. The marathoner from Ireland. The second amendment advocate who was finding out information for her brother. The guy who just wanted to stop thinking about cancer and get back to riding his motorcycle with his wife. I am honored that you reached out to me and trusted me with your stories. I save all of those emails, and every now and then I think about writing to you to ask how you are doing. But I don't, because maybe you're in a place where you don't want to think about all of this anymore. And I respect that. 

But I'd also love to hear from you if you're still reading. I'd love to now that you're doing OK. 

Cancer is such a long, strange trip if we're lucky. I hope all of you are able to make happy memories and have some time to reflect on them. And maybe smile a little.

 

Epcoritamab + B-R

The journal HemaSphere published new research last week on another Epcoritamab combo. It's an early trial, but it could be an effective treatment for some patients.

Epcoritamab has been getting a lot of attention lately. If you've been a regular reader, you know I've been saying for a few years that that the treatments that seem to get oncologists most excited these days are CAR-T and Bispecifics. And he bispecific that gets them most excited is Epcoritamab.

A quick reminder: a bispecific works by targeting two different proteins. One of them is on the surface of the cancer cell. So it works a lot like Rituximab, which also targets a protein on the cancer cell. But a bispecific also targets a different protein on a different cell -- a T cell, which is an immune cell. So bringing a cancer cell close to an immune cell, the bispecific helps the immune system work against the cancer. 

Epcoritamab works by targeting the CD20 protein on the cancer cell (just like Rituxan does) but also the CD3 protein on the T cell. It works very well, and there are more and more reports of it being used successfully in various combinations (like the recent presentation on Epcoritamab + R-Squared).   

In this research, the combination is Epcoritamab + Bendamustine + Rituxan. As many of you now, Bendamustine is a traditional chemotherapy. The article from HemaSphere is called "First-line treatment with epcoritamab in combination with bendamustine plus rituximab induces sustained remissions beyond 3 years in patients with follicular lymphoma." 

It's a pretty straightforward title. The article describes a phase 1b/2 clinical trial (meaning it looks at safety, like a phase 1 trial, but also effectiveness, like a phase 2 trial). The study involves 25 patients from the trial who have been diagnosed with Follicular Lymphoma but had not yet received any treatment. The patients received Epcoritamab + BR and thenwere given additional Epcoritamab for up to 2 years. 

At a median follow-up of 41.3 months, the Overall Response Rate and the Complete Response Rate were both 96%. In other words, 24 of 25 patients had a Complete Response. That's very high, and I can't remember any trial where the OR was the same as the CR. And at a median of 36 months, 87% of patients had kept that Complete Response. The 3 year Progression Free Survival was 83%, and the 3 year Overall Survival was 96%.

As for safety, the combination did not produce any new side effects, just the ones that were expected with either Epcoritamab or BR. However, those expected side effects were not minor. There was no high-grade Cytokine Release Syndrome (CRS) or ICANS (Immune Effector Cell Neurotoxicity Syndrome), which are perhaps the most serious possible side effects, though lower-grade CRS occurred in 68%. But there were other side effects. 92% of participants reported infections (a sign of a weakened immune system),   with COVID-19 being the most common (patients were enrolled in 2021). Injection site reactions in 56%. Fatigue in 52%. The most common grade 3side (more serious) side effects were infection (44%), and low white blood cell counts. In all, 72% of patients experienced a grade 3 or higher side effect of some kind.

The researchers point to the high CR rates and long duration as very positive things. But they also point out that a combination like this can potentially bring about serious side effects, and caution doctors to think very carefully about which patients would benefit from it instead of a different treatment with less serious side effects.

It's a small study, very early in the process, but probably justifies moving on to a larger study. It will be very interesting to see if the side effects become an issue. Epcoritamab is part of our future, no question. But how it ends up in our future -- as a single agent or in some combination -- will be worked out over the next few years.

 

Vitamin D and Cancer: No Easy Answers

The Journal of the American Medical Association published an article that this week that disappointed a lot of people. It's called "Addition of High-Dose Vitamin D₃ to Standard Treatment in Patients With Metastatic Colorectal Cancer: The SOLARIS Randomized Clinical Trial (Alliance A021703)." The hope was that taking high-dose vitamin D along with standard chemotherapy would improve outcomes in this specific group of colorectal cancer patients. Unfortunately, it did not improve Progression-Free Survival. 

The study looked at high-dose (8000 IU for two weeks, followed by 4000 IU daily) versus standard-dose (400 IU daily). There was a small PFS benefit for the high-dose group, but it wasn't statistically significant.

This isn't a study about Follicular Lymphoma, or any other kind of blood cancer, so it doesn't say anything directly about how vitamin D would affect those of us with FL. But studies of cancer and vitamin D always catch my eye because it's one of those interventions that people have asked me about fairly frequently over the years. There have been some tantalizing studies that get our hopes up. For example, in 2022, a study of Diffuse Large B Cell Lymphoma patients found that those with low Vitamin D levels had a lower response rate to CAR-T and a lower Overall Survival after 2 years than patients with normal vitamin D levels.  But that's not the same thing as saying vitamin D will improve outcomes if you already ave normal levels. Another study from 2019 found that Lymphoma patients who had higher sun exposure (and thus more opportunity for the body to naturally develop vitamin D) had a smaller risk of developing some kinds of Lymphoma, including FL. But they also found that getting vitamin D through food or supplements didn't have any effect. And then in 2018, there was a presentation at ASCO on a phase 3 clinical trial comparing FL patients who received Rituxan + vitamin D versus just Rituxan. I never saw results from the trial, which typically means it wasn't successful.

There are more. You can put "vitamin D" in the search box at the top of the blog to see more. But it's more of the same -- studies that show there might be some benefit maybe to some small population in some particular circumstance. I get these reminders every now and then that I need to step back and ask why I'm doing things and consider what I believe.

To be very clear -- I'm not saying you shouldn't take vitamin D. It has all kinds of health benefits. The National Institutes of Health have a nice comprehensive sheet that describes some of those benefits. 

But keep reading -- it also describes some of the problems that come from excessive vitamin D intake.

The point here is that it's worth knowing what your vitamin D levels are, and working with a doctor to figure out what that means for your own overall health. But I wouldn't expect it to cure your cancer. 

This is also a good time to remind you that I am not a medical doctor or a cancer biologist, and you shouldn't take medical advice from me. The best person to take medical advice from is your own doctor. They know you best, and they have the expertise to help you.

All of that said, I do take vitamin D every day. I tested low a few years ago, and my doctor recommended supplements. My vitamin D levels are normal now. I still take a fairly high dose every day, and that keeps me within normal range. In fact, it's at kind of the lower end of normal range, which suggests that my high dose is what I need. There's something happening in my body that keeps my levels low without the supplement. 

What is that thing that keeps my levels low? I have no idea, and I'm not going to worry about it. The very easy and fairly inexpensive intervention that my doctor recommended is doing its job. 

As I said, I like to have a reminder every now and then -- even a negative one -- that there are no easy answers, as much as we'd like there to be. The best we can do is stay informed, work with our doctors, and trust the excellent research that is being done.

 

Cancer Medicine Approvals in the US

The medical journal JAMA Oncology published a research letter a couple of days ago that I found really interesting. A "research letter" is a kind of informal discussion of research results, very different from the long articles that report of clinical trial results. But it provides some historical content for cancer research as a whole that should be very encouraging for all of us.

The article is called "Cancer Medicine Approvals in the US," and it looks at the circumstances surrounding the approvals of cancer treatments by the FDA for the last 20 years (from January 1, 2006 to December 31, 2025). The research focused on treatments for solid tumors, so there were no blood cancer treatments involved. There are also no pediatric treatments or generic drugs or biosimilars.

But even without the blood cancer treatments that would be most relevant to us, it still gives us a picture of the kinds of trends that have happened in the last 20 years. I think those same trends are probably true for those other treatments that aren't included in the data.

The researchers found that from 2006 to 2025, the FDA approved 385 different cancer treatments for solid tumors. Of those, 154 (40.0%) were for brand new treatments, and 231 (60.0%) were for new indications for approved treatments. For example, a treatment might have been approved for a first-line breast cancer treatment that was already approved for relapsed breast cancer. 

Another breakdown: of the 385 approvals, 105 (27.3%) were approved through the Accelerated Approval process. This means they were approved using data from a smaller phase 2 clinical trial, rather than a larger phase 3 trial. Accelerated Approvals are granted when a treatment meets a particular need that isn't being met by any other available treatment. That number is lower than I would have expected. It seems like there are lots of Accelerated Approvals these days for blood cancers, and they don't always work out well. So I feel a little better knowing that about three quarters of approvals are from the regular process. Accelerated Approvals often work out great, but they concern me sometimes. 

Another interesting bit of data: Traditional chemotherapy accounted for 40% of all approvals from 2006 to 2010. However, for the last 5 years, they have accounted for only 3.9% of approvals. This is not at all surprising. We can see it in blood cancers -- R-squared, CAR-T, bispecifics, monoclonal antibodies. All of them are proving to be good alternatives to traditional chemotherapy. They are more targeted, so they do less damage to non-cancer cells and have a different set of side effects. And even though the word "cure" was recently applied to R-CHOP, an immunochemotherapy combination, the excitement lately comes from those non-chemo options. 

Another interesting bit of information from the research is about endpoint markers. These are the data that ultimately proves whether a trial is a success or not. The best endpoint should be Overall Survival -- how many patients were still alive after 5 years or 10 years or whatever length of time they need to compare to. If a treatment keeps more people alive, that should be the measure of success, right?

It's more complicated than that. Only 102 of the 385 trials (26.5%) had Overall Survival as an endpoint. And that number is declining -- it went from 40% of trials from 2006 to 2010 to 18.7% from 2021 to 2025. Instead of Overall Survival, most trials used a "surrogate endpoint" -- a different statistic that shows "success." In blood cancers, especially in Follicular Lymphoma, the surrogate endpoint is often PFS -- Progression Free Survival, or the number of patients whose disease did not get worse over a period of time. This makes sense for FL -- if the Median Overall Survival is now 18-20 years for FL patients, it could take much too long for a treatment to be approved. No drug company is going to wait 20 years for the data they need to get approval. So while PFS isn't a perfect surrogate, it's good enough for FL.

For this research on solid tumor treatment approvals, PFS was the most common surrogate from 2006 to 2015 (60% of all trials). But from 2016 to 2025, the most common was Response Rate (46.7%). This strikes me as more problematic. A response to a treatment is great. But some responses last only for months. At least PFS typically goes on for a couple of years. Of course, I understand that not all PFS measures are long, and not all Response measures are short, and some for some cancers with few treatments available, any response is a big success. It's all more complex than these numbers suggest. But in my observation, it seems like PFS, and not Response Rate, is the primary endpoint for most new treatments, which is good.

One final bit of data comes from the way trials are constructed. Many consider the "gold standard" for clinical trials to be a randomized, two-arm controlled trial. This type of trial involves randomly splitting patients into two groups. One group gets the "standard of care" -- the treatment that is accepted as the best available at the time. This is the "control" group. The other group gets whatever new treatment is being tested. In this way, the researchers can guarantee that the two groups are the same and that a fair comparison is being made between the old and the new. The alternative is a "single arm" study. There is no direct comparison because there is only one group. The data from the trial is compared to another trial that took place in the past. There is no guarantee that the old and the new are the same. It's much easier to run a single-arm study like this, and they are more common in phase 2 trials than phase 3 trials.

This research found an increase in approvals based on single-arm trials -- 12.9% from 2006 to 2010, up to 40% from 2021 to 2025. 

The researchers conclusion says "Continued decline in the proportion of approvals based on overall survival, increase in response rate–based approvals, and underutilization of the accelerated approval pathway all reveal concerning trends." Interesting that they want to see more Accelerated Approvals. 

As I said, this research doesn't include blood cancers, but the trends that they see are pretty close to what I have observed over 18 years of paying attention to the research on FL. I'll admit that I have become kind of a Clinical Trial Nerd over that time, and I have some definite opinions about some things. But I will also remind you that I'm not a doctor or a cancer researcher, so keep that in mind.

The big lesson for me in all of this is that FL has a number of treatment options available to us. The whole reason I've become such a nerd is that there is so much research for me to read. So even when a treatment doesn't get approved, or gets pulled after approval, we still have other options. Don't ever lose sight of that. 

Stay well. More soon. 

EHA: Surovatamig + Rituxan

 I'm still sifting through some of the abstracts from ASCO and EHA from last week, and I found another one from EHA (the European Hematology Association's annual meeting): "SUROVATAMIG (AZD0486) PLUS RITUXIMAB IN PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA (FL): INITIAL SAFETY DATA FROM THE PHASE 3 SOUNDTRACK-F1 TRIAL."

(The EHA puts its titles in ALL CAPS.)

I don't know much about Surovatamig, which was previously known as AZD0486. I written about it only once before in the blog -- a description of a phase 1 trial that was reported on at the 2024 ASH conference.  Surovatamig is a bispecific, like Epcoritamab and Mosunetuzumab. It works by attaching itself to a cancerous B cell by grabbing on to the CD19 protein on the surface, and then also grabbing on to a T cell by the CD3 protein. In this way, it brings together the cancer cell and the immune cell that can eliminate it. 

The EHA presentation reports on results of a phase 3 trial called Soundtrack-F1. Let me say first of all that "Soundtrack" is a very cool name for a clinical trial. Maybe that's just because I love music so much.

Anyway, the study is looking at Surovatamig combined with Rituxan. It is a phase 3 study, with the goal of recruiting over 1000 Follicular Lymphoma patients who have not yet received teatment, though this presentation looks only at 43 of them. According to the U.S. government's clinical trials website, it has not begun recruiting trial participants in the U.S., which might be why I haven't heard much about it. Once this smaller trial is finished, the larger phase 3 trial will begin.

Still, even with only 43 patients, the researchers had some good things to present at EHA. The focus here is on safety rather than effectiveness -- reporting on the side effects experienced by the participants. The combination is interesting --  Surovatamig targets CD19, while Rituxan targets CD20. So there seems to be, at least in theory, that the two treatments would compliment each other well when used together. But any combination of treatments also means there is the possibility of doubling up the side effects.

For this study, the researchers looked at two different dose levels of Surovatamig, and divided the patients into two groups. It's very early in the trial, so median follow-up was about 6.3 months. The first group, which had a lower dose of Surovatamig, had a 95% response rate. The second group, with the higher dose, had a 100% response rate. At the time that they cut off the data to analyze it, 75% of patients in the lower dose group and 100% of patients in the higher dose group had no Minimal Residual Disease.

As for safety, 100% of patients had Treatment-Emergent Adverse Events (TEAEs), meaning side effects that develop after the treatment has been given. The most common were infusion-related reactions (36% in group 1 and 52% in group 2), mostly due to the Rituxan (not surprising to any of us who have had Rituxan). Other common side effects were fatigue (36% and 43%), muscle aches (36% and 38%) and low white blood cell counts (36% and 38%).

More serious side effects occurred in 18% of the lower dose group and 29% of the higher dose group. Cytokine release syndrome (CRS) occurred in 36% and 38% of patients and one instance of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) occurred in each of the groups. 

The study was specifically designed as a "safety run-in," a smaller study to test for side effects before the larger study happens. It's interesting to me that this is happening in a phase 3 study; that kind of dose escalation (testing different doses to find the best combination of safety and effectiveness) usually happens much earlier. In this case, there wasn't much difference between the two doses in terms of safety, but there was a slightly better effectiveness with the higher dose, so that will be the recommended dose for the larger phase 3 trial.

The larger phase 3 trial will be a randomized two arm study. Half of the patients will receive the Surovatamig + Rituxan combination, and the other half will receive Immunochemotherapy (R-CVP + Rituxan maintenance, R-CHOP + Rituxan maintenance, or Bendamustine + R + Rituxan maintenance). 

There are a couple of takeaways for me. The first is that Bispecifics are clearly going to be in our future as FL patients. This kind of large study isn't messing around -- they're looking for full FDA approval. Lots of newer treatments try to get accelerated approval, and they do that with smaller phase 2 trials and aiming at Refractory/Relapsed disease. This trial has neither. That tells me that Bispecifics are fully mature.    Epcoritamab and Mosunetuzumab are pretty well accepted at this point.

The other thing that strikes me is the care that is being taken to focus on safety. As far as I can tell, there has not been a phase 1 or 2 trial for this combination, but that's probably because there are already known side effects for both of the treatments involved. Still, with so much already known about other Bispecifics, it's a help the the researchers to know what to look for in this type of treatment.

As always, looking at this kind of research being presented at medical conferences tells me that we have lots to look forward to. Not every treatment in a trial will ultimately be approved. In fact, less tan 10% will likely be. But there is still lots being tested, and lots of good stuff coming.

 

MGUS

If that title is confusing, don't worry -- I'll explain. I want to talk a little bit more about what happened at my last appointment with my oncologist.

I wrote about my appointment a few minutes after I got home, so I was still kind of processing it all. Let me go back about 8 months or so.

During my annual physical in the fall (with my general practitioner, not my oncologist), most of my blood work was fine. But my protein level was a little bit high. That number is really general -- there are lots of potential proteins in the blood. The Gen Prac ordered another blood test to see if it was some kind of one-time thing. 

The second blood test showed the same thing. The general test didn't say much, but the Gen Prac said it was somethng we should keep testing for to keep an eye on. At this point, I was getting close to my January oncologist appointment. I mentioned it to him (the Gen Prac and the Oncologist are not on the same Electronic Records system, so he didn't see the blood test results easily). The Onc looked through the test results and ordered some additional tests on the blood test I had done for him earlier that day.  The results came back the same.

So the oncologist ordered some additional, more sensitive tests to see what exactly was happening with the excess protein in my blood.  

At this point, he kind of repeated what the Gen Prac said -- excess protein like this can be a sign of several conditions, including blood cancers. It sounded very general and non-committal to me, given how detailed our discussions usually are. But I also was not in any mood to ask what it all meant, so I let it go.

But he did give it a name -- MGUS, meaning Monoclonal Gammopathy of Unknown Significance. (And if you are a fan of the move The Princess Bride, and that immediately reminded you of ROUS -- Rodents of Unusual Size -- then you and I have something in common.) 

MGUS, as he explained, occurs in about 5% of people over 50. There is about a 20% chance of it turning into something else within 20 years. He told me not to worry about it. We will be actively monitoring for it.

Fast forward to last week. I did a blood test for my Gen Prac a few weeks ago, and the protein level was fairly stable -- a tiny increase. She wrote a message in my Electronic Records about my cholesterol looking good. No mention of the proteins. I took that as a good sign.

The Oncologist did the same general protein level test, and then the more sensitive one. Another increase.

This time he was less non-committal. "So I'm now treating you for two blood disorders -- Follicular Lymphoma and MGUS. It's possible that the MGUS could turn into Multiple Myeloma. We will continue to monitor it and treat it if it becomes necessary."

This wasn't a shock. I've known about this for 6 months. It's not like Lympho Bob isn't going to hear something like that and not start doing research.

But it was still a little bit of a punch to the gut. I put it out of my mind, mostly, but a few days later, my wife and I were on a long car trip to see our son, and it kept creeping into my head.

It brought up a lot of old feelings, things I haven't really felt much in 18 years. The fear never really goes away. It's always just under the surface, bubbling up a little bit when it gets triggered. But this wasn't bubbling up. This was a small gush. It subsided eventually, and when my wife and I had another 4 hour drive on the way home, we talked about it. She had the same feelings return when the Oncologist started to talk about it. 

It helps to try to step back and look at things rationally. And that's not always easy, I know very well. But I did a little more research. The protein levels are indeed high. A normal range is something like 3 to 8 (I'm not even going to look up what the actual range is). Six months ago, mine was something like 8.7. This time it was something like 8.9. Patients with Multiple Myeloma can have levels in the hundreds or even thousands. I'm not there yet.

The more sensitive test of the protein showed that it was the type that leads to the least aggressive problems, if any problems do occur. So that's good news. 

Another potential problem is damage to the kidneys, which have to work harder to eliminate all of that excess protein. The Oncologist had me do a urine test. I got the results back last week. His nurse left a voice mail message saying the Onclogist thought "everything looked good."

So I'm relaxing a little bit now. No immediate danger.  

But it's amazing how much the body remembers, how that same feeling in my stomach returns, how a bit of electricity and heat rises from chest, up my shoulders, into my ears. That fear. It knows its path. It knows how to return. It's ready.

As I have said many times before, I think sharing our stories is one of the most important things we can do. It helps us. It puts the fear into words. That's an important step in dealing with things. Words can be dealt with. Feelings stay where they are and fester. 

But telling our stories helps each other, too. I don't know how many times I've been on both sides -- the teller and the listener -- and realizing that two people sharing the same experience make us both feel a little less alone. Our stories help others realize that there is someone else out there who has felt as we felt. That helps.

And I hope this has helped. It's OK to feel that fear every now and then. And it's more than OK to put it into words and share it. 

Stay well, and keep sharing. 

 

NCCN Guidelines

It's been a while -- I don't like to go more than a week without posting. I've been busy, traveling to see some family and hosting other family members. Exhausting but fun. I wouldn't have it any other way.

But it means I'm behind on reading about Follicular Lymphoma. So I'll do my best with this one (and also mention that I'll be hosting and traveling for another week or more, so expect another delay).

As I look through all of the links that I have been collecting, the one that stands out is a video from The American Journal of Managed Care's website. It's from a series of interviews with Dr. Ryan Haumschild, Dr. Christina Poh, and Dr. Tara Graff. In the series of videos, he provides some insight into newer approvals for Follicular Lymphoma treatment. If you've been reading the blog for a while, you know I like this kind of thing, which is fairly common on oncology websites. It gives an expert a chance to tell us where we are -- a nice overview of what is happening.

The series includes nine videos, but it is video number 7 that intrigues me: "NCCN Guidelines in Focus: Key Updates for Follicular Lymphoma and Their Impact on Formulary Decisions."

The NCCN is the National Comprehensive Cancer Network, a group of 34 cancer centers that work together to produce a series of guidelines for doctors to help them make treatment decisions for many different cancers. The guides are based on current research about the best order to use different treatments. I'd link to the FL guide, but you need to sign in to read them. I can occasionally get to a copy, so I've seen what they look like.

The NCCN Guide for FL are interesting because they provide so many options. There are probably cancers that have guidelines that say "If a patient is diagnosed with stage 3 of this cancer, then treat them with X." Pretty straightforward. Of course, FL isn't like that. There are a bunch of options at every stage. In some ways, that's good -- we have lots of options. In other ways, it would be really nice to have a straight path with one option because that one option works so well.

What intrigues me about NCCN guidelines is how they are used. As I have mentioned before, in my 18 years with FL, I have seen five different oncologists. Three were Lymphoma specialists, doing research on FL and other Lymphomas. The other two were generalists, treating blood cancer patients, but also patients with breast, colon, and other cancers. Those generalists are the ones that seem to rely most heavily on the guidelines, which makes sense. After I stopped seeing one of those generalists, I found a copy of the NCCN guidelines and kind of traced our conversations through the guide. For example, he really wanted me to have a PET scan, even though there was no indication that my disease was progressing. But the NCCN guidelines said that someone in my position can have one every year, so it was OK. Now "can" is not the same as "should." I didn't get the scan, but I did get some insight into how he made his decisions. I also got a new oncologist soon after that. 

So the discussion of the updates to the NCCN guidelines was especially interesting to me. It's a short video -- the main update was that Tafasitimab + R-Squared is now in the guidelines. This combination was approved just over a year ago by the FDA, though honestly, I haven't heard much about it since then. Most of the buzz since then has been about Epcoritamab, the bispecific that was recently approved by the EU in combination with R-Squared. (Dr. Haumschild expects this combination to be approved and added to the guidelines soon.)

I liked his insight into why all of this is important. As more treatments are added to the guidelines, they are likely to be used more. And as they are used, more "real word" data is collected on how effective and safe they are outside of clinical trials. And as more data is collected, we get a better sense of which treatments are appropriate for which patients. The NCCN guidelines are based on just that kind of data.

But data doesn't tell the whole story. Oncologists are human, and have their habits and their opinions, and "the best" isn't necessarily the treatment that the data would suggest.

I guess for me, the lesson for all of this is, first, be sure you are comfortable with your oncologist. Ask questions. Have discussions. In many ways, we are lucky to have a slow-growing cancer, and one of those ways is that we often have time to have those conversations before treatment is needed. The other lesson is, seek second opinions when you can. The guidelines offer lots of options, and it's nice to have a second set of eyes look through the records and make a suggestion. 

Things will slow down for me soon, I'm sure. I'll get back to reading more of this FL stuff then. 

 Take care.

 

Oncologist Appointment

I had a six month appointment with my oncologist today. Things look good (with some complications).

*******

As usual, I have had mixed feelings about my appointment. I feel fine, but it's still never fun to go t the cancer center.

For all of my appointments, I have a blood draw about 30 minutes before I meet with my oncologist. At the end of one appointment, I schedule the next one, and the blood draw, too. For some reason, I didn't do that last time. I booked my oncologist appointment, but not my blood draw. I'm not sure what I was thinking. I have a blood draw clinic near me that is run by the cancer center's network, so maybe I was thinking that I could save time by doing it a day before? I don't know -- that was six months ago. 

So when I got the reminder email a week ago, and the offer to pre-check-in on my Electronic Records portal, I saw that my blood draw wasn't scheduled. So I spend a week trying to figure out how to book the blood draw at the cancer center. It all worked out, but it seems like there is always something to add extra stress to the appointment. 

For this appointment, I asked my wife if she wanted to come with me. It's actually the first time in many years that she's come to an appointment. I almost always did appointments on Tuesdays, which was convenient for my work schedule, but not convenient for my wife's schedule. The after a while, she thought it might be bad luck to come, since my appointments had been going so well. It had been so long, she hadn't ever even met Dr. H, who has been my oncologist for a while. But she agreed to come with me.

It was nice to have her with me. I don't feel like I need the direct emotional support that I used to need, but it's still nice to have someone by your side. Plus, she sees and hears things that I don't because I'm so focused. And I don't mean things like the doctor's instructions. I mean things like overhearing someone else walking down the hall saying "I hate this place" ("You and me both, lady," was my wife's comment). Or noticing that the July 4th/World Cup decorations in the blood draw office looked like it was set up so people could take fun selfies with it, and then offering to take my picture, which she did:

 

For some reason, no one else at the cancer center blood draw office seemed interested in taking a fun holiday-themed photo. Go figure.

Anyway, my blood looked mostly good (more on that in a minute), and the physical exam was fine. No problems with the Follicular Lymphoma. 

But then there are the other problems.

For my last visit, Dr. H asked for some additional analysis for my blood because my total protein was too high. The analysis broke down the various proteins in the blood to see which one was causing problems. It turned out to be IgG, signalling a condition called MGUS -- Monoclonal Gammopathy of Unknown Significance. It's a benign condition that usually stays benign, though it can have some health consequences, the  most serious being the possibility of it leading to Multiple Myeloma, another blood cancer. For now, he says that there is maybe a 20% chance of that happening in the next 20 years. But the good news is, we are aware of it, and we can test it every 6 months to stay on top of it, so if it does turn into something else, we should be able to catch it early and deal with it. It was actually my General Practitioner who first noticed it, so my regular blood tests with her are also being analyzed for the same issue on top of the lipids, blood sugar, and everything else that she tests for. 

I don't particularly want to have to deal with Multiple Myeloma, if only because I would feel compelled to write about it. And then what am I supposed to do, start a new blog? "Myelo Bob"? I don't like it. Doesn't roll off the tongue the way "Lympho Bob" does. So I'm just not going to deal with it.

Dr. H says that it's unlikely that the MGUS is related to the FL, so if you're worried that this is something you or a loved one needs to pay attention to, you probably don't need to worry. I'm just special.

I hope all of you are getting good news at your own oncologist appointments, and that you are staying well. Take care of yourselves.

 

Donate to the Pan Mass Challenge

Hello everyone. I'm going to do something I very rarely do -- ask you for money.

It's not for me. It's for all of us, really. 

My brother is once again riding in the Pan-Mass Challenge -- a bike ride across Massachusetts to raise money for cancer research at the Dana Farber Cancer Institute in Boston.  

He's been doing this ride for 18 years, and he has raised over $88,000. Occasionally, he says "This year will be my last." It's a lot of work to train and ride on the day. Last year, he couldn't ride because he was injured, and it seemed like he was done. But here he is again. He just can't help himself. He knows how important this is. 

This is the email he sent out this year:

 

I hope you had a great July 4th Holiday weekend!  We're only 4 weeks out to this year's Pan Mass Challenge , and I'll be riding again for my 18th year.  

The PMC raises more money for charity than any other single event in the country, $1.125 billion since 1980 and $78 million in 2025 alone! This success is the result of a lot of people riding for, and caring about, a cure. And because every penny matters, 100 percent of your donation goes to Dana-Farber Cancer Institute. I've made a personal commitment to ride PMC 2026 and raise $4,000.00. I hope you can help me achieve this significant goal. To give online, you can use the following link to go to my personal fundraising site: http://www.pmc.org/profile/MM0386 Every donation brings us closer by the mile. Many thanks, Mike

PMC donations are tax deductible and 100% will go to Dana-Farber Cancer Institute. The PMC's tax ID / EIN is 04-2746912. The Pan-Mass Challenge only uses your personal information to thank you and will not share it with any other organizations.

 

I know not everyone is able to donate, and that's OK. But if you're inclined, please consider clicking the link and giving a little something. It doesn't need to be a lot. And it helps us all.

Thanks for considering the request.

 

Electronic Records, Data Sharing, and Identity

I have an oncologist appointment next week. I have one every six months, and I like it that way. My oncologist says I  an see him once a year, but I feel better seeing him more often, even if I'm feeling fine and I'm not having any problems. I'll be sure to give you all a report next week after the appointment.

As usual, I received an email a few days ago, asking me to go to my Electronic Health Records and make sure everything was correct. The list of medications and the list of diagnoses get longer every time I look at them. I guess it happens with age. Everything was fine. 

About the same time, I needed to have a blood test done for another doctor and another condition. This doctor's office has its own Electronic Health Record. I think I deal with 4 different EHR systems. 

One thing surprised me, however -- my Follicular Lymphoma diagnosis. It says I have grade 3 FL with extranodal activity. That's not correct. I have grade 1/2 disease, and no extranodal activity. 

My immediate thought was panic. It didn't last long, but I thought, "Did my last blood test show something and no one told me?" But that thought didn't last long. A blood test wouldn't show any of that, and I know for sure that I haven't had a biopsy recently. So the panic came and went pretty quickly.

But I thought about it some more, and decided it shouldn't be dismissed. It wasn't in my oncologist's EHR. It was in my general practitioner's record, which matters less, since she doesn't treat me for cancer. My guess is that someone entered the information in my record after looking at old notes, and mistook stage 3 (which I am) and grade 3 (which I am not). As you probably know, stage is determined by location of disease, usually determined by a scan. Grade is a measure of how aggressive the disease is, usually determined by a biopsy and looking directly as the cancer cells.

So why is this important? Well, accuracy is always important in medical records. And I've had a bunch of inaccuracies over the last few years that I can't explain easily. If someone is looking at a "conditions" page because they're trying to determine something like which treatment or medication to recommend, they may base it on comorbidities. In other words, if there's something inaccurate about a kidney condition, they may recommend a more aggressive treatment for another condition -- or maybe a less aggressive one. So accuracy just matters in general, even if it's about a condition that isn't being treated by a particular doctor.

Another reason accuracy is important is because of potential voluntary data sharing. There are more studies happening that rely on data sharing. In other words, researchers can learn a lot by looking at large numbers of patients' records. The Follicular Lymphoma Foundation did a webinar on this a few months ago. It's a really interesting way to contribute to research without being a part of a more traditional clinical trial. But for this to be valuable, the data has to be accurate.  

But there was something else that bothered me about the mistake. It's less about medical accuracy, and more about identity. I've spent 18 years as a stage 3, grade 1/2 Follicular Lymphoma patient. It's who I am. Obviously, that changes over time for many of us. We have successful treatment. Or treatment unfortunately stops working, and we need a new biopsy and a re-staging. FL is a notoriously unstable disease. I'm sure over 18 years I have gone up and down in stage.

But that's never been official. No biopsy, no scan in about 8 years. So the stage 3, grade 1/2 is who I am. And I don't like someone else telling me who I am.  And that's what that mistake was doing. 

It's a little strange. As much as I have enjoyed being a cancer advocate, I would have preferred to have not had the cancer diagnosis. I'm sure I would have been able to find something else fulfilling to do. So taking that diagnosis off of my Conditions page would have been just fine. But it's there. And I own it. And I don't want anyone else messing with it.

So I suppose the lesson here is to take some time to make sure everything is accurate on your Electronic Health Records -- all of them. I don't always pay attention to all of the details on them. They're like Terms and Conditions when you download an app -- just scroll through them and say Yes at the end so you can get to that doctor's visit that much faster. But the details matter, for now and for later.

 

CAR-T and Cures

The big news this week in the Lymphoma World is an article that was published in the New England Journal of Medicine yesterday. It describes long-term follow-up of patients with B Cell Lymphoma, including some with Follicular Lymphoma, who received CAR-T. The results were very encouraging, and that "C word" ("cure") is being used again. More on that after I describe the article. 

The article is called "Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas." It presents results from 38 patients -- 24 who were diagnosed with Diffuse Large B Cell Lymphoma and 14 with Follicular Lymphoma, all of whom had refractory/relapsed disease (so they'd had at least one previous treatment).  They received just one infusion of the CAR-T treatment Tisagenlecleucel (also known as Tisa-cel or Kymriah) a median of 10 years ago. It's a pretty small study, but it has some important results.

I'll stick to the FL patients' results, since that's what most of us are here for. Almost half of the FL patients in the study had gone 10 years without a relapse. And for patients who had gone 5.4 years without a relapse, they continued to be Lymphoma-free after that. Most relapses occurred within the first year after treatment. 

I'll put this into a little bit more context. Early research on CAR-T treatments had kind of a 33/33/33 breakdown. For about 33% of patients, the treatment didn't work at all. For another 33%, it worked for about a year or less. And for the final 33%, it worked for more than a year. Those numbers aren't exact, but they're roughly accurate, and it's how I often think of CAR-T's effectiveness early on. Those numbers have also gotten better over time. So now, in this study, we're at 50% rather than 33% for long-term effectiveness. I can't see a breakdown for the other 33/33 groups, but they have to be smaller. 

Of course, CAR-T isn't perfect; half of the patients in the study did not have good long-term results. And there were side effects, too, to deal with. Two of the 38 patents had long-term low white blood cell counts, but there were no cases of long-term low red blood cells or ongoing anemia or low platelet levels. But perhaps more importantly, 9 patients developed a second cancer (including 3 with Acute Myeloid Leukemia, 2 with prostate cancer, 2 with lung-cancer (possible smoking-related), one with melanoma, and one with a T-cell lymphoma that affects the skin. All together, that is a higher incidence of cancer than the general population, though it is similar to the incidence for Lymphoma patients who received traditional chemotherapy.

What's most interesting about this to me is a press release from University of Pennsylvania Medicine, where the research occurred. Here's where the "C word" comes in:

Most relapses occurred within the first year after CAR T cell infusion, supporting the hypothesis that patients who experience a long-term response to CAR T cell therapy may be cured. "As oncologists, we use the word ‘cure’ with great care, but I am increasingly confident that CAR T cell therapy has the potential to cure a meaningful number of patients with B-cell lymphomas,” said senior author Stephen J. Schuster, MD, the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research and director of Penn’s Lymphoma Program. “At the same time, our work is far from done. This therapy does not yet work for everyone, and we are committed to understanding why so we can continue to improve the next generation of CAR Ts."

It's interesting to see both of things happening here -- that the word "cure" is used, and that the researcher is cautious about using it.

It certainly brings to mind the research that was published a few months ago that suggested a 15 year follow-up after R-CHOP might show that some patients were cured. I was hesitant to use the word "cure" then and I'm still hesitant to use it now. 

That's not to say it isn't possible, but it's still hard for me to wrap my brain around, 18 years after I was told it was incurable.

Last month, the Follicular Lymphoma Foundation published a blog post called "Could Some People with Follicular Lymphoma Be Cured? New Evidence Sparks Careful Optimism." It reports on an interview that the FLF's Chief Medical Officer, Dr. Mitchell Smith, conducted with the lead researcher on that study, Dr. Jonathan Friedberg. (They are both Lymphoma Rock Stars, by the way. I'm going to start using that label again, I think.)

I'm actually quoted in the blog post. And since I love to quote myself, here's part of what I said: "It opens up a whole new way for patients to think about FL: that some of us might be cured. I was diagnosed over 18 years ago… and I haven’t needed treatment since. I might fall into that category of patients who are cured, and yet I still have that small little bit of doubt and fear in my head."

I think that explains my feelings pretty well. Here's another quote from me: "It's going to take some courage from both doctors and patients to change our way of thinking...but what an exciting future it will be."

I think that explains things pretty well, too. I suspect we're going to see more long-term studies of FL treatments very soon. They are a lot easier to conduct than clinical trials -- all of the data is already collected. And I suspect we'll see a lot more doctors using the word "cure" as a result.

What an exciting future it will be, indeed. We have lots to look forward to. 

 

Jamie Reno

I want to take a quick break from ASCO and EHA to write about Jamie Reno, who died in April. 

I used to write about some people as Lymphoma Rock Stars -- people who did great things for the Lymphoma community, whether they were doctors, researchers, patients, or something else. Jamie was a Lymphoma Rock Star.

I didn't find out he had died until a couple of days ago. Jamie was a long-time journalist, and his most recent job was as editor of Breaking Cancer News, which I wrote about a couple of years ago.  The folks at BCN sent out an email to their mailing list, with a really nice tribute to him, two months after he had died. From what I can tell, his family wanted to keep things kind of quiet, and there wasn't much about it online. I looked at the Living with Follicular Lymphoma Facebook page to see if there was any news there, but there wasn't. There was nothing on the discussion board/support group that helped me so much 18 years ago. I thought maybe some old-timers there might have heard something. But there wasn't anything.

I'm not criticizing the family's decision in any way. As patients, we deal with our cancer in the way that makes most sense to us. And as family's, we mourn our loved ones in the way that makes most sense. I've been in the unfortunate position to have to decide how to mourn both of my parents' deaths from cancer. 

But at the same time, Jamie Reno really was a Lymphoma Rock Star, and I feel like there should be something said about that. I never met him, didn't know him, but he was definitely a presence in my life as a Follicular Lymphoma patient.

In 2008, when I was diagnosed, if you googled Follicular Lymphoma, one of the first things that came up was Jamie Reno's book Hope Begins in the Dark. It's a collection of 50 stories from Lymphoma patients and survivors. He was a life-long journalist, writing for Newsweek for 23 years, and winning a National Magazine Award as part of the Newsweek team that wrote about 9-11. He was a cancer survivor himself. He was diagnosed with an aggressive form of FL when he was 34, and went through CHOP. He was in remission for over 2 years, and when it came back, he tried Bexxar, a RadioImmunoTherapy. It gave him 28 years of remission. At some point, he left Newsweek and devoted himself to writing about cancer. In addition to Hope Begins in the Dark, he also wrote a book called Snowman on the Pitcher's Mound, about a 10 year old boy whose mom is diagnosed with cancer. The mom character's experience with cancer kind of parallels Jamie Reno's experience with relapsing and receiving RIT.

He was a musician, too, managed to get some great musicians to play on a CD that he put out.  

With all of the stories he helped to tell about cancer, it seems like his needs to be told to the people who haven't heard it before.

Death is always hard. Even the death of someone we never met can break of a small piece of us.

But maybe that little piece that is gone can be replaced by hope. That was certainly a message that Jamie Reno seemed to want to pass along. The email that I got from Breaking Cancer News talked about how much he emphasized the "good news" about cancer -- breakthroughs in treatment, positive stories about survival and courage, and the importance of hope.

The title of his book, "hope begins in the dark," echoes a quote from the writer Anne Lamott. I honestly don't know if she said it first, or if it came from somewhere else, but here's what she said: "Hope begins in the dark, the stubborn hope that if you just show up and try to do the right thing, the dawn will come. You wait and watch and work: you don't give up."

That's a fitting message for cancer patients, and especially for those of us living with Follicular Lymphoma, who do plenty of watching and waiting and working and not giving up.

Our stories matter. As I said, much of my FL experience had Jamie Reno's story lingering over it, in very good ways. It always helps to have a model, someone who has been there and has done OK, someone who has been in the dark and found a way out.

I try to be that for other FL patients. Now you know why.   

 

EHA: Epcoritamab and R-Squared

A reader asked me a couple of weeks ago if I reviewed presentations from the EHA Congress, the annual meeting of the European Hematology Association. It's the European equivalent of the ASH meeting in the United States. It happens soon after the ASCO conference. I have written about some EHA presentations in the past, but as I told him, I sometimes have trouble accessing their abstracts. So it hasn't been something I have done on a consistent basis. EHA has some excellent research. But it's always been a matter of access.

This year, I figured out how to look at EHA abstracts. And I had some incentive -- I got many notices about a particular presentation, "CLINICALLY RELEVANT SUBGROUP ANALYSIS FROM THE RANDOMIZED PHASE 3 EPCORE FL-1 TRIAL: TREATMENT (TX) EFFECT OF EPCORITAMAB WITH LENALIDOMIDE AND RITUXIMAB (R²) IN R/R FOLLICULAR LYMPHOMA (FL)." 

The presentation is an update on the EPCORE FL -1 clinical trial. I wrote about this a few months ago. 

First, some background. Epcoritamab is a bispecific, meaning it has two mechanisms working. On one side, it attaches to a protein on the surface of the cancerous B cell, and then also attaches to a protein on a T cell, an immune cell. In this way a bispecific uses the body's immune system to treat the cancer.

The EPCORE FL-1 trial is a phase 3 trial involving 488 patients with relapsed or refractory Follicular Lymphoma. Half of the patients received R-Squared (Lenalidomide + Rituxan) and the other half received R-Squared + Epcoritamab. The earlier results from late last year, with a median follow-up of 14.8 months, showed an Overall Response rate for the Epcoritamab group of 95% (versus 79% for the R-squared group). The Complete Response Rate was 83% for Epcoritamab and 50% for R-squared. The Progression-Free Survival for the Epcoritamab group was higher, with estimated PFS of 16 months in 85.5% of that group versus 40.2% in the R-squared group. 

The updated results break down the comparison into some sub-groups to determine if the Epcoritamab combination holds up better for certain populations. What the researchers found was that Epcoritamab + R-Squared seems to work better than R-Squared alone no matter how they divided things up. 

The results were better for the Epcoritamab group regardless of the age of the patients. For patients under 70 years old, The ORR was 96% versus 78% for the R-Squared group, and the Complete Response was 84% versus 50%. In patients 70 or older, the ORR was 91% versus 81% and the CR was 79% versus 50%. 

When patients were divided into low versus intermediate/high comorbidity (with the NHL-5 scale, a measure of how other health issues like heart, lung, or kidney disease might affect survival), the Eporitamab group again did better. Those with low NHL-5 comorbidity in the Epcoritamab group had an ORR of 94% versus 76% for the R-Squared group, and a CRR of 81% versus 50%. In the NHL-5 High/intermediate group, the ORRs were 97% versus 84% and CRRs were 86% and 49%.

The same held up for patients who received one previous treatment (ORRs were 96% vs 80%, the CRRs were 87% vs 53%,) as well as two or more previous treatments (ORRs were 94% vs 78%, the CRRs were 77% vs 45%). 

All of that matters, of course, because it shows that the Epcoritamab combination will work no matter the population. One big concern for a "triplet" like this  -- a combination of three different treatments -- is that there is the potential for three times the side effects. Patients who are older, or who have other health problems, or have been weakened by multiple treatments may have more problems with a triplet. But that wasn't the case here.

One more breakdown of the data in this presentation had to do with Lenalidomide, which has the potential for dangerous side effects. As part of the study, the researchers tried different levels of Lenalidomide -- at full strength, at 70%, and at 50%. But even with less Lenalidomide, the Epcoritamab triplet did better than the R-Squared. 

So, to sum up, Epcoritamab on its own is very good. R-Squared is very good. Combined, they are all even better, without sacrificing safety. 

I still have a few more ASCO presentations that I'm sifting through. I'll try to do the same with EHA presentations as well. More to come soon.