Options for Relapsed/Refractory FL (Videos)

Cancer Network has recently added to their video series called "Growing Options for R/R Follicular Lymphoma."

The series features several short videos of a conversation between four Lymphoma specialists: Dr. Brian Hill of the Cleveland Clinic; Jennifer Garson, a physician assistant at Rush University Cancer Center; Dr. Muhamad Alhaj Moustafa of the Mayo Clinic; and Dr. Tycel Phillips of the City of Hope Cancer Center.

The series actually begins with a written interview (not a video) with Ms. Garson, who talks about dealing with some of the side effects of treatment. Episode 2, the first video, introduces the speakers and focuses briefly on the evolution of treating FL, with each participant talking about how the field has changed. Ms. Garson, for example, talks about Rituxan and the ways it changed treatment and improved Overall Survival. Dr. Moustafa talks about the changes from the last 5 years or so, with the introduction of treatments like R-squared and bi-specifics. Dr. Phillips adds CAR-T to the list, and says he is "excited to see where things are going."

(I will add that one of the reasons I like video series like this is for just what Dr. Phillips says. It's always great to see Lymphoma experts get excited about the work they do and what we might see in the future.)

Episode 3 looks more specifically at a case study -- a 65 year old woman with Follicular Lymphoma. Dr. Hill goes through her symptoms (some of them will sound familiar!), and her diagnosis of stage 4 grade 3A FL, and the panel suggests what they might have done if they had seen this patient. 

I enjoy this kind of thing, too. I'm not a doctor -- it's been a little bit since I have reminded you all about that -- but I like to guess what the doctor may have suggested. I guessed R-squared for a first treatment -- a cancer that's not too aggressive, but chemo seems old-fashioned for this group. And then CAR-T or a bi-specific if it returned. 

And I was wrong. The actual patient was given Bendamustine and Rituxan, which Dr. Moustafa called "the standard of care right now" (which is probably accurate). They debated whether or not R-CHOP would be appropriate, if it had been more aggressive on the PET scan, and transformation was a possibility.

Then they asked about what to do next, and they debated R-Maintenance, which they agreed was controversial and appropriate for some, but not all, patients. (Part of that decision has to do with the pandemic, and being more careful about messing with patients' immune systems. It has apparently changed quite a bit since the pandemic, with more oncologists being cautious with Maintenance.)

And if the FL returned? In the case study, the patient relapsed after 4 years, with grade1/2 FL coming back. They had several possibilities -- one chose R-Squared (or maybe Revlimid with Obinutuzumab instead of Rituxan). They wanted to hold off on R-CHOP until it was needed for transformation. Other possibilities were plain Rituxan or possible pathway inhibitors, though they are usually used for a 3rd round of treatment, or a clinical trial.

The lesson here, everyone? Be glad that I'm not your doctor. I'd probably get your treatment plan wrong. 

They do also talk about CAR-T, though they thought this was a fairly aggressive treatment, as was Stem Cell Transplant, and bi-specifics. Some of those would probably come later, as a 3rd or 4th line of treatment. Additional videos talk about some of these other options. You can find all of them on the page linked above.

It's very interesting to me that the doctors in this series were much more conservative than I had guessed they would be. Reading so much about newer treatments, it's easy to get caught  up in the excitement about them. But when it comes to actual doctors treating actual patients, the tried-and-true treatments, the ones that they know will actually work, are the ones that they recommend. The newer, more exciting stuff comes later on, when they patient has fewer options.

Change comes slowly in lots of places, including oncology. I don't think that's a bad thing. There's a big difference between getting excited about bi-specifics at a conference with other oncologists, and deciding whether to recommend a treatment that was approved just a few months ago to a scared patient who is sitting in your exam room. The conservative approach makes a lot of sense to me (and, to be honest, was the approach my own oncologist took, and which I happily agreed to.)

The series continues with more discussions of newer treatments, and then with a return to the case study of the 65 year old woman who had B-R. But this time they imagined that she didn't get a 4 year remission. Instead, it was only 4 months.  That makes her POD24 -- immunochemotherapy that stopped working within 24 months. These patients have a much lower median OS. What to do?

I won't share what my guess is with this one, or whether it lined up with what the doctors on the panel recommended. 

But I will say that the whole series was a great reminder that a laptop isn't a treatment room, and a patient-blogger isn't an oncologist. Remember that -- the best source of information about Follicular Lymphoma, and how it affects you as a patient, is your own doctor.

Understanding the Immune System

I've been going back into my files, looking at some of the older things that I set aside to look at later. Well, it's later now. Here's an interesting piece published about a month ago on OncLive.

It's an interview with Dr. Stephen Ansell from the Mayo Clinic in Minnesota, who talks about the challenges of understanding the immune system, and how greater understanding might lead to better lymphoma treatments. The interview is based on a presentation he made at the SOHO (Society of Hematologic Oncology) meeting in September.

As Dr. Ansell points out, the immune system is very complex. There are several different immune cells, and they serve different functions, targeting different invaders, working in sequence or together to fight infection. While we know the basics of how those cells work, we're only really just beginning to understand how to harness their power to treat cancer. You can see their promise when you think about the two types of treatments that get Lymphoma experts most excited right now -- CAR-T (which changes immune cells in a lab so they can detect cancer cells) and bispecifics (which bring immune cells into close contact with cancer cells). 

So when you consider that those treatments have been very effective, but not completely effective, one question to ask is, when they stop working, is it because of some issue with our not understanding completely how immune cells work? In other words, if CAR-T works well and gets a Complete Response, but then stops working, what changed? In theory, T cells have a memory -- once they encounter their target, they will remember it for the next time it shows up. So what happens with refractory CAR-T (when it worked but then stopped working)? Do they stop remembering? Did they change in some way? Those are the kinds of questions that need to be answered.

And, of course, there are questions that go beyond CAR-T and bispecifics, which target CD 19 and CD20 proteins on cancer cells. Another type of treatment being developed uses a different kind of immune cell called a macrophage, even more powerful than T cells. Macrophages can target yet another protein, CD47.

Then there is the question of treatment sequencing. If certain treatments are given after others stop working, do they have a negative effect on the immune system, in ways that prevent other immune-cell-based treatments from working effectively? In other words, if chemo messes with the immune system, will that make CAR-T less effective later on, because it involves the immune cells that need to be changed to find the cancer cells?

And what about treatment combinations? Would adding, say, Rituxan to another immunotherapy create problems? There's always the danger of increased side effects with combining treatments. But will one of those side effects be lessening the effectiveness of the immune cells that are being used to treat the cancer?

I find it all very fascinating. I always thought, way back in school, that the immune system was interesting. I thought it was strange that we had this kind of second blood system, the lymphatic system, that no one ever talked about. Now here I am with Lymphoma. Isn't life funny?

But I do find it all fascinating, and I'm glad that lots of researchers do, too.  I'm sure we'll see lots of improvements to current treatments, and maybe some new treatments, coming out of all of this research in the next few years.

Minimal Residual Disease and Cancer Blood Tests

 I' have two related things that I want to talk about. One's been sitting in my email inbox for a while, and the other has been sitting on my kitchen table. They both have to do with blood testing as a way to detect cancer.

The thing in my email is a story from MedPage Today called "Final Results From PATHFINDER Study of GRAIL’s Multi-Cancer Early Detection Blood Test Published in The Lancet." This one is very cool. It describes the clinical trial results for a blood test called Galleri, which may be used to detect multiple cancers, possibly while they are asymptomatic. It's the "multiple" part that is getting people very excited. From a simple blood sample, the test can detect whether or not the patient has one (or more) of several cancers. The results look very promising, especially since about half of the patients that the blood test found potential cancer in detected the cancer at stage 1 or 2, when treatment is likely to be more effective. Another promising statistic -- 74% of the cancers found were for cancers that do not have a recommended screening (the way something like breast or colon cancer has a recommended screening). 

It's not a perfect test, but it's good enough that it could be very valuable for early detection for a lot of people. It's really a first step -- signalling that something should be checked out more carefully with other testing. It's less invasive that a lot of other tests might be.

The other thing that I read recently is an article from CURE magazine. It's called "On the Lookout for Minimal Residual Disease in Leukemia." It has a similar theme -- a blood test can help detect "minimal residual disease" after treatment for blood cancer. In other words, a patient might seem to have their cancer completely cured because a PET scan isn't picking up any cancer cells. But the blood test can pick up tiny amounts of cancer that a PET scan can't, letting the doctor know that a little more "salvage" treatment might be necessary. It could take months or years for the little bit of leftover cancer to show up on a scan, so the test can find it while it is still more manageable.

Both of these items highlight the kind of "liquid biopsies" that have been making a lot of noise lately. They both work on the same principle -- they can find changes in DNA in cells that send a signal that something isn't right. 

It's kind of amazing that we're able to look at such small pieces of ourselves, and it reminds me of how far we've come in a fairly short time. I remember my own biopsy. I had surgery under general anesthesia so the surgeon could remove a lymph node in my hip for testing. I was limping for a week. (I went into work the next day even though I wasn't supposed to.) The sample went to a lab, where it was looked at under a microscope  and determined to be Follicular Lymphoma. So in some sense it was worth the trouble. But if it had come back negative, that would have been unnecessary invasive surgery.

Now, this isn't to say that a liquid biopsy would completely eliminate the need for a physical biopsy. I don't think we're there yet. Someone who took the blood test and got a result for, say, pancreatic cancer might still need a scan and a biopsy to determine what was really going on. But the test has the potential to catch that cancer early. That's a wonderful thing.

My guess is we'll be seeing more research results in the next few years for MRD testing and liquid biopsies in FL. Some might be describing new tests, some might be testing what already exists. But the technology seems to be getting better all the time. Particularly for post-treatment testing, it seems likely to be a part of our testing kit in the very near future.

Good stuff.

LRF Educational Programs

As I've done in the past, I'd like to alert you all about some upcoming webinars and educational programs presented by the Lymphoma Research Foundation. I have found them very helpful, and I hope they may be helpful for some of you, too.

One of the most interesting programs that the LRF offers is their "Ask the Doctor" series. This is just what it sounds like -- the chance to hear briefly from a Lymphoma expert and then ask specific questions. At one time (pre-Covid), the LRF held in-person sessions. I went to one of them near me a few years ago. But I think they might all be online now. These are not recorded, so if you're interested, you have to tune in live.

There are four "Ask the Doctor" sessions coming up in the next few months:

• Ask the Doctor About Lymphoma: Information for Newly Diagnosed Patients – October 19, 2023, featuring Dr. Tanaya Shree of Oregon Health and Sciences University
• Ask the Doctor About Lymphoma: Information for Relapsed/Refractory Patients – November 16, 2023, featuring Dr. Ayushi Chauhan of Augusta University Health
• Ask the Doctor About Lymphoma: Information on Treatment Options and Clinical Trials – December 5, 2023, featuring Dr. Christine Ryan of the Dana-Farber Cancer Institute
• And finally, a program in Spanish: Pregunte al doctor sobre el linfoma – 21 de diciembre del 2023.
  Presentador: Dr. Jorge Castillo, Dana-Farber Cancer Institute

Clicking on those links will take you to the LRF we page for each of the webinars, where you can register.

the LRF is also offering a national virtual program called "Lymphoma Workshop: Understanding Lymphoma Basics and Current Treatment Options" on Saturday, November 4, 2023. this is an all-day workshop, from 9:30am to 3:00pm EST. There are a whole bunch of presenters for this, with a few sessions for specific Lymphoma subtypes. A few particular sessions look especially interesting.

The first is a session on Follicular Lymphoma and Marginal Zone Lymphoma from Dr. Thomas Habermann from the Mayo Clinic.I'm sure there will be some nice updates on newer treatments.

The other that looks great to me is called "Lymphoma Survivorship" with Dr. Carrie Thompson, also fro the Mayo Clinic. I've heard her speak before on Survivorship, and I follow her on Twitter/X. I think she's great, and her research is on survivorship and life after treatment. Should be a good one.

Of course, all of these are free.

I like LRF's programs because they usually feature some very good doctors and researchers who know exactly what is happening in the world of Lymphoma. But at the same time, they also know how to explain things in language that patients can understand. It's a rare combination in a doctor.

I hope some of you get a chance to attend. And if not, remember that a lot of LRF's programs are archived and available to watch any time.

Enjoy.

Skin Cancer Diagnosis

Well, folks, it's official -- I have a secondary cancer.

I went to my dermatologist about a week ago, and she biopsied a growth on my scalp. Results came back a couple of days ago, and it's Basal Cell Carcinoma. 

And, in my mind, it's not too big a deal. 

For one thing, I've been kind of preparing emotionally for this for about two years. My current oncologist has been encouraging me to go to the dermatologist for at least that long, reminding me that as a Follicular Lymphoma patient, I am at greater risk of skin cancer than most people. FL, as you know, is a cancer of B cells, a type of immune cells, which makes my immune system a little bit more "special" than others'. And since the treatment I received has a way of messing even more with the immune system  (this is true of pretty much every FL treatment), it's no surprise that I have had some cells behaving in ways they shouldn't. And misbehaving cells can lead to cancer.

It's also not a surprise because I grew up at a time when sunscreen just wasn't a thing. I had regular sunburns as a kid -- red skin, blisters, peeling, can't-sleep-because-the-sheets-hurt-when-they-touch-your-skin kinds of sunburns. In fact, I was about 22 when I last got one of those. I should have known better by that point, but it was the summer before I met my wife and I was still a self-destructive jerk. She changed me for the better. My point is, that combination of funky immune system and a history of sun damage makes for perfect conditions for skin cancer.

It was almost exactly a year ago when I wrote about my last close call with skin cancer. My dermatologist did a biopsy then, too, fearing I had a different type of skin cancer -- squamous cell. That one turned out to be negative, removed just before it was likely to turn cancerous. This one wasn't so quick. 

The good news is that Basal Cell Carcinoma is the most common type of cancer in the USA, with about 3.6 million diagnoses every year (according to The Skin Cancer Foundation). It is non-aggressive, and as long as it is treated soon, it shouldn't cause any major problems.

I'm scheduled for surgery in about a month -- no hurry, no worries. It will be in an-office procedure with a local anesthetic. I'll write more about it after it happens. If I was 40 years younger, I'd document the whole thing on Instagram. I probably won't do that.

The lesson here, as I said a year ago -- pay attention to your body and do any scheduled cancer screenings that your doctor recommends. Colonoscopy, breast or prostate exams, skin tests -- all of it.

I think most of us FL patients are probably aware of our own bodies, and we know when something isn't right. That's the "blessing" of having a slow-growing, incurable cancer. We pay attention. But I also know that many cancer patients finish treatment and then just don't want to think about it anymore. I get that. But make sure there is a balance. Don't think about cancer for 364 days of the year. For the other day, get whatever prevention and detection tests are available.

And remember to urge your family and friends to do the same. Tell them your story. Embellish it if you have to. I'm all in favor of shame, guilt, and fear if it gets someone to the doctor's office for a cancer screening.

I'll keep you all updated. Probably won't be much to tell, which is how I like it.

Stay well. Get checked.

FDA Priority Review for Odronextamab

Big news in the Lymphoma community -- the FDA has granted Priority Review for Odronextamab.  It's being reported on most of the major oncology news sites. 

Odronextamab is a CD20 x CD3 bi-specific.  As a reminder, a bispecific works like a monoclonal antibody like Rituxan by seeking out a protein on the surface of a B cell called CD20 (just like Rituxan). But it also targets the CD3 protein on T cells, a type of immune cell that will be floating in the blood along with the B cells. A bi-specific will attach to both and bring the T cell in contact with the cancerous B cell and help the immune cell to eliminate it. Right now, the only bi-specific available to Follicular Lymphoma patients is Mosunetuzumab.

The Priority Review is based on phase 1 and phase 2 clinical trial results. I first started writing about Odronextamab about four years ago, when it was still known as REGN1979. The application is for both Relapsed/Refractory FL and DLBCL (that is, the patient's last treatment stopped working or did not work at all). Patients need to have had at least two previous treatments.

Results have been very good. In the phase 2 trial, patients with Follicular Lymphoma had an Overall Response of 82% and a Complete Response of 75%. The median duration of response was 20.5 months and the median Progression Free Survival was 20 months.

As for safety, 100% of the 131 patients with FL experienced side effects (which isn't surprising -- all cancer treatments result in side effects), and 78% of them experienced grade 3 Adverse Events (more serious side effects). The most common side effects were Cytokine Release Syndrome (over half of patients), low blood cell counts, diarrhea, fever, joint pain, and infusion-related reactions. None of the CRS were grade 4 or 5, which are the most serious.

So it seems like the side effects are manageable. 

If you've been reading for a while, you know that bi-specifics (along with CAR-T) are the Lymphoma treatments that get oncologists most excited. Given some of the issues that Lymphoma treatments have been having in the last few years, I would expect a very thorough vetting by the FDA. The target date for a decision by the FDA is March 31, 2024. I wouldn't be surprised if we saw some updated trial results at ASH in a few months; the last time any results were presented was at last year's ASH. And I would expect it to be positive (maybe updated numbers on duration of response).

Definitely one to keep an eye on.