Treatment Options for Follicular Lymphoma

OncLive published another of their great video series a few weeks ago. I like these series -- they provide some very up-to-date information, and they usually bring in different oncologists to give their perspective for each new series.

This series is called "Recent Updates in the Treatment of Follicular Lymphoma and Mantle Cell Lymphoma." Like all of their video series, this one is meant for oncologists, not patients. But if you keep up with current treatments, it's not hard to understand.

There are 10 videos in the series, and it is structured around treatment lines. In other words, the first video talks about current treatment options for first line -- for patients who have never had treatment for their FL. Then there are videos focusing on second and third line treatment options. This series features a bunch of oncologists. There's Dr. Grzegorz Nowakowski of the Mayo Clinic, Dr. Jennifer Crombie from Dana Farber, Dr. Matthew Lunning from The University of Nebraska, Dr. Peter Martin from Weill Cornell, Dr. Laurie Sehn from the University of British Columbia, and Dr. Bijal Shah from the Moffitt Cancer Center. An excellent group.

The link above will take you to the first video, though the other nine appear right below it. (Unfortunately, this series does not include a transcript.)

The focus is on newer research presented at recent conferences, but really, the discussion is about what's been available for a while. In the first video, the oncologists talk about how they approach a treatment decision for a patient who has never had treatment. This includes watching and waiting for patients with no symptoms. For other patients, depending on their health, this could include just Rituxan, especially if the patient is older and has other health issues. But for younger, healthier patients, some type of traditional chemotherapy might be a good choice. Still other patients, who don't want chemo, they might choose R-squared.  And of course, clinical trials are always a consideration. For one of the oncologists, probably half of the FL patients she sees do not have an aggressive disease, and can watch and wait or try Rituxan. This allows more time to consider a treatment path.

The other videos in the series do talk about some of the other options, especially those that had new data presented at the ASH conference. The videos are about 5 minutes each, give or take a minute. Together, they present a pretty good overview of where we are right now in our options for treatment.

Important to consider -- these videos were recorded soon after the ASH conference in December, even though the videos themselves were posted over several weeks after that. Some of the recent issues related to CAR-T are not included in the discussion. I'm sure there will be some discussion of that in another video series.

The panelists are excited about bispecifics, and see them as a third-line possibility, though they are also seeing more evidence that they could work as first-line treatment. There is also some discussion of Zanubrutinib, the BTK inhibitor, with its surprisingly good data for FL.  

Lots of good stuff here. If you're looking for a good summary of where we are for treatment, this is a good place to be.

Take care.

New FDA Warning for CAR-T

There was some bad news for CAR-T treatments issued yesterday -- the FDA called for  "Black Box Warning" for CAR-T treatments. These would include the CAR-T treatments that have been approved for Follicular Lymphoma. 

This follows reports from November that some CAR-T treatments were leading to T Cell malignancies. In other words, with the treatment that involves changing T cells to find and eliminate cancer cells, those T cells could turn cancerous themselves. 

There's a lot to unpack here, and I'm trying to be rational about it all. 

First, the FDA's action. Issuing a "Back Box Warning" means they are adding a literal black box or border to the packaging insert of the treatment. The black box is meant to make it stand out and be noticed. The warning is considered the highest safety-related warning that the FDA gives, and it usually means that the treatment can lead to severe side effects. There are currently over 400 approved treatments, including many cancer treatments, that have Black Box Warnings, and the warnings can be changed or removed over time as new data becomes available.

The FDA warning came because a large number of patients who have taken CAR-T treatments have developed T cell cancers. In the letter that the FDA sent to manufacturers of CAR-T treatments, they said that they have become aware of this risk and that the new cancers have "serious outcomes, including hospitalization and death." How many patients have developed new T cell cancers? I can't find a definitive number, but it may be as high as 22. That doesn't seem like a lot compared to the thousands who have received treatment, but it's enough to issue the warning, especially since they develop over time. Doctors have been asked to be especially vigilant with CAR-T patients and continue to monitor them, even after they have been in remission for some time. 

The call for the Black Box warning isn't complete. The manufacturers have 30 days to respond to the FDA, with changes they will add to the labels, or a statement of why they think the label warning isn't necessary. 

So what does this mean for Follicular Lymphoma patients?

I'm not really sure. As I have said before, I'm not an oncologist or cancer researcher.

But really, I'm not sure even oncologists know at this point. It's very new, and they seem to be digesting the news (at least in the conversations I am seeing online).

Any new Black Box warning makes doctors take notice, obviously. They need to rethink the kind of risk/reward calculations that they always make when considering a treatment for a patient -- essentially, will this treatment create more problems than it solves? Every treatment has side effects, some more severe than others, some that affect certain patients more than others. That's not going to change. But they're going to have a lot more to think about.

Some interesting reactions online that I have read:

• This may lead some doctors to recommend CAR-T for older patients, if T cell cancers develop many years later, rather than younger patients who will be at greater risk.
• This may lead researchers to create "kill switches" on the T cells, so if they turn malignant, they can be more easily killed off (don't know if that's even possible).
• There is still a lack of data over the relationship between CAR-T and the new cancers. In other words, researchers are still looking to see if the T cells that were changed as part of the treatment are even the same T cells that turned cancerous. That's extremely important data to have. 
  
• At least one oncologist who I respect a lot says CAR-T will still be a great help to many of his patients, and that the new cancer is "low risk."
• Another said the rewards of CAR-T far outweigh the risks, especially since CAR-T is often used now for patients with "dire prognosis."

So as I said, I'm trying to be rational about it all. In my own case, CAR-T isn't something that my oncologist and I have discussed for me right now. Maybe that changes over time. And maybe by then, there's more data about this issue to help make a decision.

So, the same advice applies as always. Have an oncologist that you trust, and have honest conversations about treatment -- your goals, your fears, and your needs. Then make the best decision you can.

No Survival Benefit with Rituxan Maintenance

The Journal of Clinical Oncology published the results of a study a few days ago that looked at long-term benefits of Rituxan Maintenance. The article is called "Long-Term Follow-Up of the RESORT Study (E4402): A Randomized Phase III Comparison of Two Different Rituximab Dosing Strategies for Low–Tumor Burden Follicular Lymphoma." The big news from the study is that there doesn't seem to be a survival benefit from Rituxan Maintenance in low-tumor burden Follicular Lymphoma patients. 

A few things need some explaining here. 

First, Rituxan Maintenance is a type of treatment where patients first receive a treatment that includes Rituxan (also know as Rituximab and Mabthera), a monoclonal antibody. The treatment could be just Rituxan, or it could be Rituxan combined with something else (like R-CHOP or R-Bendamustine). For this particular study, the patients received only Rituxan, once a week for four weeks. The "maintenance" part comes next, after the initial treatment -- patients receive just Rituxan on a regular schedule for a certain time period. For this study, the patents recieved Rituxan every 13 weeks until they need treatment again. (Some Rituxan Maintenance studies have a different dosing schedule, like every 2 months for 2 years, and then no more.)

The idea behind Maintenance is that the regular doses of Rituxan will help "clean up" any leftover cancer cells, or any new cells that develop. It's always been kind of controversial, with some studies showing a benefit and others showing no benefit, and others showing a small benefit but asking if the additional cost and additional weakening of the immune system is worth it (Rituxan reduces cancerous B cells, which are part of the immune system, but also healthy B cells).

For what it's worth, my own treatment, 14 years ago, was 6 weekly rounds of Rituxan. I haven't needed treatment since. I do remember asking my oncologist, as we discussed treatment, if we should consider doing maintenance. Back then, he told me that there was good evidence that maintenance helped people who had received immunochemotherpay (R-CHOP or R-Bendamustine, or back then, R-CVP, which is less common these days), but less evidence that there was a benefit for people who received only Rituxan.

What seemed like the case, 14 years ago, is confirmed by this research, which looked at a long-term follow-up of patients like me, with low tumor burden, receiving only Rituxan.

I'll repeat this, because I think it's important -- this study looked only at low-tumor burden FL patients who received only Rituxan. There's a whole other body of research on patients who had high tumor burden, or who received other treatments (though they are controversial in their own ways -- you can search for what I have written about them over the years). 

For this study, 289 FL patients were divided into two groups, as I mentioned above. The first group received four weeks of Rituxan, and then no other treatment until their disease returned and got bad enough to need treatment. The second group received Rituxan, and then more Rituxan every 13 weeks until it stopped working and they needed a different treatment. 

The Maintenance group did have some benefits to their treatment. After 7 years, 83% of the patients who had received Maintenance had still not needed a second treatment. In the first group, only 63% of patients had been able to avoid treatment.

Also, some patients had their disease return, even though they didn't need a second treatment yet. After 7 years, 71% of the Maintenance group had not had their disease return, while only 37% of the non-Maintenance group remained in remission.  

But it was Overall Survival that showed no difference. After 10 years, 83% of the Maintenance group was still alive, as was 84% of the non-Maintenance group. 

And the OS was what the researchers focused on. And of course, that's important. We all want to live longer. But I think the other numbers are important, too, and I have some thoughts about them.

This seems like a good time to remind you all that I am not an oncologist or a cancer researcher. The best person to talk to about treatment decisions is your own oncologist.

It seems to me that patients who receive only Rituxan are in a situation where they have a less aggressive version of FL. This was certainly the case for me. And while we do have some treatments that have the potential for very long-term remission, or even A Cure, we're not really there yet. So there may be some FL patients whose goal is to stay in remission for as long as possible. They know (or assume) that they will eventually need treatment again, and they want to delay it as long as possible. Maybe a Maintenance strategy is the best way to do that -- a relatively less aggressive treatment at first (compared to something like traditional chemo), followed by less aggressive treatments for a while. Of course, doing this also costs money, and increases the chance for infection, but also holds off more aggressive treatment for a while.

I'm not endorsing Rituxan Maintenance for anyone. I'm not endorsing any particular treatment at all. My point is not only that your oncologist is the best person to talk to about this, but also that your a very specific discussion of your goals should be a part of that conversation. Not everyone is looking for A Cure. Maybe your life style or your overall health make that difficult. But that's the ind of topic that should be a part of your oncologist visits. It is for mine. Even after 16 years, I want to know what the next steps might be, if I ever need them.

We are fortunate to have lots of choices. It's good to know what they are, and which is best for each of us.

 

16 Years

Today is my 16th diagnosiversary.

I was diagnosed with Follicular Lymphoma 16 years ago.

It has also been 14 years to the day that I started my first round of Rituxan.

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My diagnosiversary is always a day for reflection. It's actually more than just a day. It usually occurs to me sometime in October or November that The Day is coming up. That's when the reflection starts. I think back over the past year and what I've seen and done and been through. I think about what kind of lessons I've learned. Sometimes it's not so much about what I'm thinking. It's just what I'm feeling.

It has been a fairly eventful year. And high on the list of "events" was getting diagnosed with Basal Cell Carcinoma, a pretty common skin cancer, in October. As I wrote about when I got the diagnosis, it was not a surprise. I'd been having some Actinic Keratoses removed from my scalp and hands for the last few years (they are small benign growths that can lead to Squamous Cell Carcinoma if left untreated), so it always seemed like just a matter of time before one of those two types of skin cancer showed up. 

Being prepared for it emotionally was a good thing. I suppose I've been prepared for it emotionally for 16 years, in a way. Hearing a doctor say "You have cancer" is always awful -- the first, second, or tenth time. For me, the first time, with the Follicuar Lymphoma, was such a shock (I was 40 years old and in the best shape of my life at the time, something a lot of FL patients seem to say). That made it seem much worse. "You have cancer" is still not something I wanted to hear again, and I hope I never hear a third time. But there just seemed to be a kind of "Here we go again" feeling with the skin cancer diagnosis. I've done this before. I can handle it.  

So the day of the surgery wasn't as awful as it could have been. I had read the description of the procedure on the dermatologist's website and watched the videos that they recommended. I've been to enough appointments, had enough scans, and sat in enough treatment room chairs to know how to calm myself on an eventful day. As I was reading around on the dermatologist website, I read the "About" section of my surgeon (he is not my regular dermatologist). It said that one of his hobbies was collecting rare wines and whiskies. I can talk about whiskey all day. So on the day of the surgery, he gave me a local anesthetic, and he and I had a lovely conversation about Macallans and Springbanks while he did the surgery. 

It was an uneventful kind of eventful day. As a friend drove me home, I remember thinking "I get diagnosed with the most boring cancers." That's not a complaint.

But a few days later, I started thinking back on the surgery. I won't get into detail, because this is different than the Follicular Lymphoma experience that we all share. Let's just say I thought about all of the sensory details of the surgery -- the sights and smells and sounds and sensations. They were not pleasant memories.

It all reminded me at that point just how violent cancer can be. As a cancer patient, I've experienced plenty of small violences, with scalpels and needles and IVs and fingers and other things that have gone into me. That's all been a part of the cancer experience for even more than 16 years, since back before I even knew that I had cancer. But something about that moment of reflection a few days after the surgery just made it all new again. 

Cancer is a hard thing to escape. It stays with you. It's harder still when you have a cancer that is considered incurable, and one that makes you susceptible to secondary cancers. I've spent 16 years coming to peace with that. It was easier the second time. I was prepared.

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Another of the big events in this eventful year was going to Italy with my wife to celebrate our 30th anniversary. We actually just finished our scrap book from the trip about a week ago, many months later. It was nice to look back at all of the pictures we took, and some of the little souvenirs like ticket stubs that we'd saved, and to look at the diary that we kept during the trip. It was a high point of the year. Of the last few years, really.

It was paid for, in part, with some Cancer Money.

As I have discussed before, I don't monetize this blog. I don't have any advertisements on it, or charge anything for it. Some cancer bloggers do, and that's fine for them. I know some of them who can't work because of their health, and ad revenue is an important source of income. I'm fortunate that I am not in that situation. I'll remind you that, if you find a cancer resource online that you need to pay for, just make sure they provide sources for their information, and the sources are legitimate. Just linking to another blog is not legitimate, in my opinion. Make sure the information you pay for is good and trustworthy. 

So while I don't make money off of the blog directly, the blog has led to some really nice cancer-related opportunities that do pay me. Some of the writing I do elsewhere is for pay, though not all of it. I've done some small consulting jobs. Once I gave feedback to medical students learning how to deliver bad news. Another time, I was a judge for a contest. None of them pay a huge amount, usually enough for my wife and I to go out for a nice dinner (but not too nice). But it all adds up over time. We put that money in a special bank account. I call it "Cancer Money." My wife wishes I would call it something else. But it has a purpose -- to have some fun experiences.

Last year, we used some of the money to buy very overpriced tickets to see Bruce Springsteen. The concert was scheduled for March, but a week before the show, half of the E Street Band came down with Covid. They rescheduled for September. Two weeks before that show, Bruce was diagnosed with a very painful duodenal ulcer and he postponed again. So now we're rescheduled  for April -- we hope. 

Cancer Money is about finding the good in the bad. If cancer is going to take from me, I'm going to be darn sure to squeeze whatever I can from cancer. And I'm going to do something fun with it. It's easy to forget that, even with cancer, we're supposed to be having fun. It helps to be prepared for that, too.

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I don't know if any of you are Bruce Springsteen fans. I recommend one of his recent albums, Letter to You, which is a really wonderful meditation on the changes that come from getting older. Bruce is 74 years old, and he's still doing 3 hour shows when he's on tour. About 40 years ago, he decided that he was tired of being exhausted after his shows, and he started to pay more attention to his health. He prepared for the life he is still living now.

But he's also 74 years old. There are things that he can't control. Covid. Ulcers. Falling down during concerts every now and then. He's probably prepared for those things, too. He gets back up and plays on.

So if there's a lesson that I have learned over 16 years as a cancer patient, it's in those two stories, taken together. There needs to be a balance in our lives. As cancer patients, as much as we prepare ourselves for the bad things, we need to prepare for the good, too. We have to be emotionally ready for whatever difficulties that cancer brings us. But we need to be ready when the good opportunities happen -- emotionally, physically, even financially, as much as we are able. 

And then we need to be brave enough to take those good opportunities when they come.

Thank you, once again, for being such a big part of these 16 years. Stay well. And stay prepared. I hope a really good opportunity happens for you soon, and that you are prepared enough, and brave enough, to do it.\

 

Oncologist Appointment

I had a 6 month oncologist appointment today.

Everything looks good.

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As I have said before, Dr. H, my oncologist has told me that spacing my appointments to once per year would probably be fine. But I like to go every 6 months. It gives me some peace of mind.

I was scheduled for blood work at 9:30am, a half hour before my appointment with the oncologist. I got to the hospital way earlier than I needed to. I always do. I'd rather be there and sit quietly than worry about being late. I'm the same way with airports. And sometimes I get lucky and everyone's schedule is light that day and I can do blood early and Dr. H will see me early and I can just get home. 

That wasn't the case today. The line at the blood draw office was very slow. The person in front of me had some kind of problem and the very talkative receptionist had to deal with it before I could be checked in. And then when I did get to the front of the line, the receptionist told me that Dr. H's office hadn't put in the order yet. So I had go up three flights and tell them, and then go back down and wait for the paperwork to go through. 

A minor annoyance, really. I still got to Dr. H's office on time for my appointment. But it was unusual. They're usually very efficient, and that threw me off a little.

Something else was a little different today, too -- everyone at the hospital was extremely friendly. That's not always the case. Sometimes the people I deal with -- office workers, nurses, security -- are very "professional," but kind of cold, too. Today they were very warm. Even the talkative receptionist in the blood draw office interrupted me to give one of her co-workers a hug. She apologized, and I said it was fine -- I'd never want to interrupt a hug. So maybe that's the trade-off? I can get cold and efficient, or warm with missing paperwork? (If that's really the choice, then I'll take the warmth.)

I was called into the appointment, led in by a very friendly nurse, who did all of the usual things -- blood pressure, temperature, weight, etc. Then I went into the exam room and waited for Dr. H.

Something interesting occurred to me as I was being led down the hall by the nurse. I've lost about 25 pounds since the fall. I've been using an app called Lose It! It's basically a calorie counter that helps me to be more aware of what I'm eating. [I'm not getting any money from Lose It! to tell you that, just to be clear.] My cardiologist had suggested I try one of the weight-loss drugs that are getting very popular, but I wasn't crazy about what I was reading about them, so I tried to do it on my own without the drugs. So far so good. 

Usually when I lose even a little bit of weight, my cardiologist and my general practitioner are very encouraging. But what occurred to me here was that my oncologist might react in the opposite way. Weight loss is, of course, often a symptom of an active tumor. So much for getting lots of praise today.

Dr. H was very quick to come in to the exam room. We talked a little about work, and travel, and kids, as we always do. I updated him on the skin cancer surgery (the dermatologist office is not in the same healthcare system as the oncologist, so there was no record of it in my online chart). And I updated him on various vaccines I had gotten in the last 6 months (which I got at my local pharmacy -- again, different online system, so no records).

I told him I was actively trying to lose weight, at the recommendation of the cardiologist. He was pleased, but also cautious. He asked me what my goal was, and I told him probably another 10 or so pounds. He took note of that in my chart, and said he was almost certain that the weight loss wasn't cancer-related, since my blood work was normal. Almost certain. It's kind of fascinating how different doctors have different perspectives and concerns.

Dr. H was pleased with things -- my blood work, my well-behaved lymph nodes, and my general attempt to be and stay healthier. As I often do, I asked him about what was happening in the world of Lymphoma treatment. He mentioned Bispecifics again, and their being approved for Relapsed/Refractory Follicular Lymphoma. And that means it would be an option for me if and when I need treatment again. He also mentioned that, given my success with Rituxan, that would be an option for me as well. But he was also excited about Bispecifics as a first treatment for FL, and said the hospital was part of the trial for that.

So I'm done for 6 months. At least with this cancer. I go for a follow-up for the skin cancer surgery in the spring. I'll be sure to update you about that as well.

I hope you all have happy oncologists at your next appointment, too. Stay well.

 

ASH Review: Long-Term Results

Welcome to 2024, everyone. I hope it's a healthy, happy year for you all. 

I'm still "cleaning up" all of the Follicular Lymphoma news items that I have been saving from the last couple of months. Here are two more presentations from ASH that are worth sharing. In the write-ups I saw after the conference, both were presented as good "long-term" results -- meaning 3 years. 

The first is #603 "Mosunetuzumab Monotherapy Continues to Demonstrate Durable Responses in Patients with Relapsed and/or Refractory Follicular Lymphoma after ≥2 Prior Therapies: 3-Year Follow-up from a Pivotal Phase II Study." 

The presentation looks at FL patients with Relapsed/Refractory disease who received Mosunetuzumab. As you probably remember, Mosunetuzumab is a bispecific antibody, so it attaches to both lymphoma cells and to the T cells that might eliminate them. The early results from this phase 2 trial were very strong (it was a phase 2 trial that led to Mosunetuzumab being approved by the FDA). By looking at these patients after 3 years, researchers were able to show that the treatment is effective over time, and that new side effects have not developed (or if they have, they were manageable).

For the 90 patients in the study, the Overall Response Rate after 3 years was 77.8%, with the Complete Response rate at 60%. The median Duration of Response was just under 3  years. In that time, 57.1% of the patients remained disease-free. Another 37.8% of them had received another treatment for their lymphoma, including 5 who received another dose of Mosunetuzumab (3 of the 5 achieved a Complete Response from that second round of he bispecific).

As for side effects, there were no new cases of Cytokine Release Syndrome (CRS) or serious side effects. Overall, side effects were comparable to those that were reported in the two-year follow-up. 

The researchers say that this follow-up shows that Mosunetuzumab remains effective and safe even after three years.

The second presentation is #601 "Clinical Outcomes of Patients with Relapsed/Refractory Follicular Lymphoma Treated with Tisagenlecleucel: Phase 2 Elara 3-Year Follow-up."Lots of interesting parallels with the Mosunetuzumab presentation above. It's a 3 year follow-up of a phase 2 trial for an approved treatment, involving R/R Follicular Lymphoma patients. In this case, it is the CAR-T treatment known as Tisa-Cel, or Kymriah. 

The trial involves 94 patients who were evaluated. The Overall Response rate was 86%, and the Complete Response rate was 68%. The median Duration of Response was not yet reached (which means more than half of the patients in the trial still had a response after 3 years). As for safety, no new side effects were reported, and the most common serious side effects were CRS, pneumonia, and neutropenia (low white blood cell counts). 

Like the Mosunetuzumab researchers, the Tisa-Cel researchers believe that the treatment has great potential. They are especially hopeful that the treatment will be effective for POD24 patients (those who relapse within 24 months of receiving immunochemotherapy).

As I have been saying for a while, it is these two types of treatment -- Bispecifics and CAR-T -- that seem to get Lymphoma experts most excited these days. And these presentations just gave them more reason to be excited. 

More good things to come. Have a great year, folks.