Follicular Lymphoma Approvals and Trials at ASH

Hello all. 

This is probably my last post for 2022, so I was looking for something appropriately "end of the year"-themed. I couldn't find anything like that, and I don't have time to come up with my own Top 10 list, so I'll offer two things that I think kind of sum up The Year in Follicular Lymphoma.

The first is a quick screenshot from the FDA list of approvals in oncology for the year. There were two FDA approvals in 2022 for Follicular Lymphoma: 

In case that's hard to read, the approvals were for 1) Tisagenlecleucel (also known as Kymriah), a CAR-T treatment approved for patients with Relapsed/Refractory FL who have already had at least two treatments, and 2) Mosunetuzumab (also known as Lunsumio), a bispecific that is also approved for patients with Relapsed/Refractory FL who have already had at least two treatments.

That seems appropriate -- two approvals, one for CAR-T and the other for a bispecific. Those seem to be the two treatment categories that have created the most excitement among Lymphoma experts over the last year. They are both very effective and fairly safe, and move us even further away from traditional chemotherapy (though chemo still has a place for many FL patients, and will for a while). 

So that's a good way to end the year -- looking back at the success that researchers have had in changing the way patients are (and will be) treated.

The second things I want to share is one more look back at ASH. This one is from the website Cancer Therapy Advisor, called "ASH 2022: Trials Show Promising Results in Follicular Lymphoma." It highlights four clinical trials that had results presented at ASH this month. 

Interestingly, the first two trials that I already wrote about: one that showed that Rituxan by itself or with maintenance can give some FL patients a long time until next treatment, and one on the bispecific Odronextamab, which had excellent effectiveness, but raised some questions about safety.

The third one highlighted in the article looks at trial results for Tisagenlecleucel (also known as Kymriah), the CAR-T treatment approved earlier this year. This ASH presentation gave some updated results. The original trial report showed that the overall response rate (ORR) was 86%, and the complete response (CR) rate was 69%. The follow-up showed that it remained effective over a longer-term, with Progression-Free Survival at 67% and Overall Survival at 95% at 12 months, and the PFS rate of 57%, and the OS rate was 88%, after 24 months. 

Interestingly, the article includes an interview with an oncologist who says that we likely won't see CAR-T used in a community setting for 10 more years. In other words, patients will have to go to a hospital for CAR-T treatment, rather than going to an oncologist's office, the way some patients can for chemo, or Rituxan, or even bispecifics. There are still just to many risks involved with things like Cytokine Release Syndrome to administer CAR-T outside of a hospital, where such problems can be handled quickly. 

The fourth presentation is for a "triplet" -- a combination of three treatments. Combinations often have good effectiveness (since they usually come at the cancer in three different ways), but often have safety issues (since the side effects from three treatments can pile up and be three times as bad).

This triplet involves Polatuzumab, Obinutuzumab, and Lenalidomide. Obinutuzumab is a momoclonal antibody, used as an alternatuve to Rtuxan. Lenalidomide is also known as Revlimid, and is part of the R-Squared combination. 

Polatuzumab is less commonly used in Follicular Lymphoma. It's classified as an antibody-drug conjugate. It's like Rituxan, in that it attaches to a protein on the surface of a B cell. But it also has a bit of chemotherapy attached to it as well, so it can deliver the chemo directly to the cancer cell (like the way Zevalin delivers radiation, or a bispecific delivers a T cell). 

This triplet is effective and durable. The PFS rate was 83.3% at 12 months, 67.4% at 24 months, 64.6% at 36 months, and 53.4% at 48 months. The median Overall Survival was not reached. Safety is a concern (as it often is with triple combinations). 86% of patients had a grade 3 or higher Adverse Event (a serious side effect), with 3 fatalities. Most patients (77%) had a side effect serous enough to lead to stop treatment temporarily, and 34% had one that led to stopping permanently.

The researchers seem to think that this combination would do well in a larger study, with one commentator suggesting it could be directly compared to R-Squared in a randomized trial.

So there we are, at the end of 2022: lots of promise from some new treatments, lots of refinements to the treatments we already have, and lots of possibilities for the future.

Progress seems slow sometimes, but I continue to think that we're in a good place as FL patients, especially compared to where we were just a few years ago.

My plan for 2023 is to continue to do what I've been doing, keeping up with news in the world of Lymphoma and sharing what I learned. My 15th diagnosiversary is coming up just a few weeks. I'll have some things to say on that day.

I hope everyone has a happy and healthy end to 2022, and a good start to 2023.   

FDA Approves Mosunetuzumab for R/R FL

Yesterday, the FDA approved the bispecific treatment Mosunetuzumab for patients with Relapsed/Refractory Follicular Lymphoma who have had at least 2 prior treatments. The treatment will go by the name Lunsumio (but I'll probably keep calling it Mosunetuzumab anyway).

The approval is based on results from a phase 2 clinical trial, so a phase 3 trial will be necessary to confirm that it works on a larger group of patients. But it will be available in a few weeks while that trial is being run.

It's a big deal. It's the first bispecific approved for FL in the United States (the European Commission approved it using pretty much the same data, back in June). As you know if you've been reading the blog, lymphoma experts have been very excited about bispecifics for a few years. Once data from trials started becoming available, it was pretty clear that bispecifics could be a game-changer -- a non-chemotherapy treatment option that uses the immune system to kill cancer cells. I've been very interested in it for a few years, since I asked my oncologist which treatments he would consider if/when I needed treatment again, and he mentioned this trial.

As a reminder, a bispecific works by targeting two proteins, one on a cancer cell, and the other on a T cell, an immune cell. Mosunetuzumab targets CD20 on the B lymphocyte that turns cancerous in patients with FL (it's the same protein that Rituxan targets), and then targets CD3 on the T cells. It brings them together so the T cell can take out the cancer cell. 

It's very effective. The phase 2 trial that led to FDA (and EC) approval showed an 80% Overall Response Rate, including 60% of patients getting a Complete Response. It was also pretty durable, with the time that the treatment lasted being a median of 22.8 months. The most common side effects were Cytokine Release Syndrome (39% of patients), and fatigue, rash, pyrexia and headache (all more that 20% of patients).

Bispecifics are often talked about at the same time as CAR-T (see my last post, for example). They do have some things in common, including that they work by have T cells go after the cancer cells. They're also different in many ways, including cost (because CAR-T needs to be made specifically for each patient, it can be more expensive). A conversation with your oncologist will help sort out which would be most appropriate. 

As I said above, the approval is for FL patients who have had two or more treatments already, so newly diagnosed patients wouldn't be eligible, and neither would I (not having had a second treatment). But it will benefit a whole lot of FL patients out there.

And of course, it's important to remember that this is a provisional approval, and if the results of the next trial show that, for example, there are some dangerous long-term side effects, then approval would be withdrawn. (It happens, unfortunately.)

But for now, there's lots to be excited about.

More ASH commentary soon.

Stay well.

ASH Review: Blood Cancer Progress

There's still a little more to be said about this year's ASH conference, and I will share that soon. 

One of the great things for me about the things that are published after a conference like this is seeing the excitement in experts' writing or hearing it n their voices, as they talk about what they have just seen at the conference. I want to share one of those commentaries. It's by Dr. Vincent Rajmukar, a blood cancer specialist at the Mayo Clinic in Minnesota (you can read his profile here -- he's clearly someone who knows what's happening in the blood cancer world).

 Right after the conference, Dr. Rajmukar wrote a Twitter thread about why he was excited about the progress being made in blood cancer research. There were a whole lot of things that excited him.

You can read the thread here. You don't need to have a Twitter account to read it -- it got collected on a different website so it could be easily read. It's just a series of short statements, but together, they really do present a whole bunch or reasons to be excited about where we are, and where we're going, in blood cancer research.

It's pretty short and easy to read, but I'll sum it up for you here anyway:

• Immunotherapy is changing everything. Our ability to understand how genes and proteins influence the immune system and its relationship to cancer has completely revolutionized the way researchers approach cancer.
• CAR-T and Bispecifics are the most exciting types of blood cancer treatments happening right now, and they are just beginning. They're already good, and improvements are on the way. They are a direct result of our understanding of genes and proteins and the immune system.
• (When I say "we" and "our," I'm obviously not including myself as part of the research team doing all this. I mean it the same way as someone from Argentina saying "WE won the World Cup!" I let others do the work and then share in the excitement.)
• That understanding of genes and proteins is also creating even more targets for future treatments. (Remember, CAR-T and Bispecifics are general categories, not specific treatments. Future researchers may find different ways to target genes and proteins in ways that improve CAR-T and Bispecifics.)
• That knowledge also allows us to find very small bits of cancer that don't show up on scans -- Minimal Residual Disease -- that could let us find recurring cancer early, making it more treatable.
• mRNA technology, the same approach that created some of the Covid-19 vaccines, is being used as possible cancer treatments as well. We'll be hearing more about that in the near future.
• Technology has allowed researchers to collaborate in ways that weren't possible just a few years ago. Teams from around the world can share data and speak to one another much more easily now.
• Patients can use technology to communicate with doctors much more easily, too. A Zoom meeting can connect a patient with a cancer expert thousands of miles away. We aren't necessarily limited to the doctors that live near us.
• I'll let Dr. Rajmukar's words stand for themselves here: " I am also totally impressed by the talent of the next generation of investigators. These are some brilliant people who are driven to find ways of improving outcomes in cancer."
• Still lots of challenges --  fancy new treatments come with high prices, some of them are/will be complex to administer (like CAR-T), lots of  new treatments means lots of clinical trials, which will require willing participants and high costs, etc. 
• But even with those challenges, there is so much to be hopeful about.
  

I was very happy to have seen that thread on Twitter. There really is so, so much to be hopeful about. And hearing and seeing it directly from a leading lymphoma expert makes it even nicer. 

More ASH information to come soon.

ASH Review: Odronextamab (Bispecific)

 First of all, a couple of photos from the ASH conference (I wasn't there, but there are a whole lot of photos from the conference on Twitter):

 

The first photo is a group of oncologist/hematologists (I blocked out their faces). The second one are the ASH mascots: a white blood cell, a drop of blood, and (I think) a macrophage, another type of immune cell. The blood mascot made an appearance last year, I think, but the other two are new. I'm glad everyone had a good time (that's what conferences are for, in addition to learning about new research). But if I was a platelet, I'd be pretty unhappy that I was left out.

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

One the bad things about not being able to go to a conference like ASH in person is that I miss out on things like photo ops and mascots. But ASH happens at the worst time of year for me for my job, and they don't offer discounted registration for independent patient advocates anyway. 

But the other bad thing is that I only get to read the abstracts -- the summaries of the presentations that I always link to. Those presentations are usually presented as posters (with a little more detail than the abstract) or oral presentations (with a lot more detail, plus questions from the audience). For the presentations that seem to make the most impact, there will at least be some discussion on Twitter, or maybe a press release from the researchers, and some discussion online immediately afterwards. 

Today is the last day of ASH, so I'm starting to see some of those press releases and online discussions. And it's clear that bispecifics are the big news for Follicular Lymphoma this year. People seem very pleased with the updated results for Mosunetuzumab, as I discussed in my last post.

But more controversial are the results for Odronextamab, a different bispecific (I gave this a very brief mention in my last post, because the results seemed good, but not overly exciting to me, based on just the abstract.

However, there are two stories being told about Odronextamab today, after the ASH presentation last night. One is very positive, and the other is a lot more cautious. 

The official story from the company that makes Odronextamab is the very positive one, as their press release makes clear. And the results do show some very good effectiveness. Odronextamab is a CD20 x CD3 bispecific -- it attached to the CD20 protein on a lymphoma cell, and then to the CD3 protein on a T cell, an immune cell that can kill the cancer cell. The results from the phase 2 clinical trial show that it had an 82% Overall Response Rate for patients with Relapsed or Refractory Follicular Lymphoma, with a 75% Complete Response Rate. Those are excellent numbers for a phase 2 trial. The company says they are the highest response rates ever for R/R FL patients, and that the trial has set a "new benchmark." And the response was durable, with the Complete Response lasting a median of 20.5 months.

But then there's the other story, which focuses on safety. As several commenters have pointed out, there are some very serious side effects with this trial. In fact, Odronextamab was put on clinical hold two years ago because of serious side effects.

One of the big side effects was Cytokine Release Syndrome (CRS), which seems common in bispecifics, and definitely in CAR-T. And there were others --- all 131 FL patients had side effects, with 118 of them related to the treatment. There were 81 serious events. There were also 17 deaths recorded during the study, with 6 of them related to the treatment (the others were for things like Covid), with causes such as pneumonia, a brain infection and a fungal infection. Another 15 patients had to leave the trial because of problems like CRS, tremor, epilepsy, high liver enzyme s, etc. The company points out that it did take steps during the trial to cut down on some of these side effects like CRS.

 

The company that makes Odronextamab is planning a phase 3 trial immediately, but is also going to apply to the FDA for accelerated approval. It has already been given Orphan Drug Designation was for FL by the European Medicines Agency (which means it will get some special help during the approval process). It will be very interesting to see what regulators have to say about the side effects. As one lymphoma expert pointed out on Twitter, Mosunetuzumab doesn't seem to have these same safety issues, despite using a similar mechanism.

So far, this has been the most-talked-about presentation from ASH this year. It officially ends today, so there will probably be more experts weighing in the days and weeks to come.

I think the big lesson here is a reminder that, for now, cancer treatments are always about the balance between effectiveness and safety. Treatments that are very good at killing cancer cells are also more likely to cause problems. It's pretty hard to avoid. Maybe someone will figure out how to do that in the future, but for now, it's about recognizing them early and managing them well. 

I'll continue to look out for expert commentary from ASH, and share what I find out. 

In the meantime, may your days be filled with large, cuddly pathogen-killing immune cells like the ones in the pictures.

ASH Preview: Bispecifics for Follicular Lymphoma

More on what's happening at ASH this weekend. 

William asked in a comment what I found interesting with bispecifics. There's actually a lot of bispecifics research being presented, some on new treatments, some on treatments that have been in trials for a while. But it's safe to say that bispecifics and CAR-T are still the treatments that get lymphoma experts the most excited these days.

As a quick reminder: bispecifics act sort of like monoclonal antibodies, in that they find a protein on a cancer cell (like CD20) and attach to it. But unlike a monoclonal antibody, they have two sides (that's the "bi" in the name), and the other side attaches to a protein on a T cell (an immune cell), allowing the T cell to eliminate it.  Very effective, and pretty safe.

Right now, there are not any bispecifics approved for use with Follicular Lymphoma in the U.S. The closest we have is Mosunetuzumab, which is currently under review by the FDA, though it has been approved by the EU. The FDA set a target date of December 29 for a decision, so we may hear something soon.

In the meantime, there are a few interesting presentations on Mosunetuzumab at ASH. For example, "610 Mosunetuzumab Monotherapy Demonstrates Durable Efficacy with a Manageable Safety Profile in Patients with Relapsed/Refractory Follicular Lymphoma Who Received ≥2 Prior Therapies: Updated Results from a Pivotal Phase II Study." The phase II clinical trial results are what the FDA will base its decision on, so this update is important. And the results are very good -- the Overall Response Rate was 77.8%, and Complete Response was 60%. And 79.5% of those with a CR remained in remission for 24 months. This treatment was given to patients with 2 or more previous treatments. When the researchers compared the results to the patients' previous treatments (chemo, PI3K inhibitors, CAR-T, or R-squared), the bispecific treatment had a better response rate, Progression-Free Survival, and time to next treatment. And in this update, there were no new major safety issues. It's easy to see why people are excited about it.

There will also be a description of a trial using Mosunetuzumab and Lenalidomide (no results yet). And in another presentation, a subcutaneous version of Mosunetuzumab is shown to be effective and safe. (Subcutaneous means it can be given under the skin, as a "shot," rather than as an IV.)

There are other bispecifics for FL that are getting attention at ASH. 

Plamotamab, for example, showed good effectiveness and safety in a phase 1 trial.

Epcoritamab is being tested on R/R Follicular Lymphoma in a phase II trial. (This is a subcutaneous bispecific.) It is also being tested in combination with R-squared.

Odronextamab is another bispecific with high response rates for FL in a phase II trial.

So, to sum things up, there might not be anything that is really game-changing about bispecifics at ASH this year. But instead of one big impressive presentation, there are a whole lot of very good presentations about bispecifics that show that it is a treatment that will probably be with us for a very long time. That's certainly the story that many are telling -- the future of FL will revolve around CAR-T and bispecifics, and since bispecifics are probably going to be less expensive, and thus maybe more popular.

Of course, we still don't have an approved bispecific in the U.S., and no real long-term data for effectiveness and safety. I'm kind of seeing shadows of PI3K inhibitors -- lots of excitement, priority review and approval, and lots of variations. And we know how that worked out. 

But I'm more optimistic about bispecifics. As a reminder, I'm no expert -- I'm not a medical doctor or  a cancer researcher. But it seems like 25 years of monoclonal antibody research might matter, since bispecifics work by a similar mechanism.

Lots to be hopeful about.

More ASH previews soon.

 

ASH Preview: The Costs of CAR-T

I saw my first television commercial for a CAR-T treatment recently. It kind of confused me a little bit, but then, most ads for cancer treatments have that affect on me. It's customary in the U.S. to include an "ask your doctor about...." statement in those ads, as if most of the population just casually brings those things up during doctor appointments ("My elbow hurts when I raise my coffee mug. Hey, what's this CAR-T stuff I saw an ad for when I was watching that rerun of Modern Family?")

But that's the way it is with our healthcare system. I have no idea if other countries, who have single-payer healthcare systems, even have such things as television ads for pharmaceutical treatments. I'm guessing you do not.

But I was thinking of that when I read an abstract for an ASH presentation called "4859 Total Costs of Care during Chimeric Antigen Receptor T-Cell Therapy in Patients with Relapsed/Refractory B Cell Non-Hodgkin Lymphoma: A Large Private Insurance Claim-Based Analysis."

CAR-T has been probably the most talked about, and most promising, blood cancer treatment in the nearly 15 years since I was diagnosed. It gets people very excited. At this year's ASH conference, there will be about 350 presentations related to CAR-T in some way. It's a big deal, as I'm sure you all know.

But one of the big criticisms of CAR-T has been the price. The treatment is developed by removing some T cells from a patient, changing them in a lab so they'll recognize cancer cells as something to be eliminated, and then put back into the patient. So each patient has their very own, personalized treatment made specially for them. So it's an expensive process, much more expensive than a treatment that can be made for thousands of people.

This ASH presentation looked at the private insurance records of patients who had received CAR-T and added up the costs. When CAR-T treatments were first approved, the manufacturers estimated that the treatment would cost roughly $450,000. (If you're not in the U.S., you can use this currency converter so you get a sense of the cost. Hint: it will be a lot.) But that $450,000 is just the price for the treatment itself. The researchers for this study also looked at all of the other costs related to the treatment, all of which were paid for by the private insurance: inpatient, outpatient, professional and associated drug costs. In other words, the costs for the doctor appointments before treatment, the costs of the drugs that help with side effects, separate fees for specialists that need to be consulted, etc. 

What they found was that the mean total cost was $618,100, and the median was $573,300. Nearly 6% of patients had a total cost of over $1,000,000. There weren't many FL patients in the study (only 6, compared to 269 with DLBCL), and their costs were higher ($611,900 for DLBCL, and $743,100 for FL).

And while the numbers are high, and awful, for patients in the U.S., this is a problem for all of us, no matter where we live: even single-payer systems will have to prioritize treatments, and make sure the effectiveness is worth the cost, or if some other treatment will a better, more cost-effective choice. 

So what's the alternative? Well, possibly an "off-the-shelf" or Allogeneic CAR-T. In other words, instead of making a personalized treatment for each patient, there could possibly be one CAR-T that could be effective for all patients. There are a number of Allo CAR-T treatments in development, including one called CB-010, which is getting an update at ASH.

One of the exciting things about ASH (and ASCO in the spring) is getting to see the small improvements that are made in treatments that have been around for a while. As great as CAR-T is, there's still lots of room for improvement, so hopefully we'll see more ways of getting this treatment to people soon.

I'm still reading. I'll post more interesting ASH presentations soon.

Oncologist Appointment Today

I know I said I was going to talk more about some ASH abstracts, and I promise that I will. 

But I had my six month oncologist appointment this morning. Everything still looks good.

I don't really have much to report. It was, as usual, difficult to get there. I see a lymphoma specialist now, instead of a general oncologist, because I wanted someone who could answer my (sometimes very specific) questions. But that means I have to go into the cancer center in city near where I live, and my appointments are usually right around the time the city gets busy. And to make it worse, the parking garage is under construction, so I almost got into three accidents while I was trying to park. 

That's not really anything that you want to hear, I know. No one likes to hear someone complain about something like traffic.

But what you do understand is that bad feeling that bubbles up when an oncologist appointment comes up. I was diagnosed almost 15 years ago, and I've thought about cancer every day since then. I don't have the fear of it that I once did. But driving to the hospital for an appointment, even having done it dozens of times, I still get that little bit of stress. And I can see it in myself -- I know when I'm stressed, I get annoyed very easily. So it's not about traffic and construction. It's about those feelings that we all have, whether we were diagnosed 15 years ago or 15 days ago.

But I have to say that the hospital I go to has gotten better over the years. By that I mean it's gotten more personal. For a while, it was all very business-y, and I felt like I was just being moved out as quickly as possible. But it's better now. The staff seem genuinely concerned about patients. I was waiting for my blood draw, and the receptionist in that office told me that if the music was too loud, just let her know and she'd turn it down. (Of course, it was Mariah Carey's "All I Want for Christmas Is You," so I told her it was fine for now, but if it happened a couple of weeks from now when I would be sick if it, I'd ask her to lower the volume.)

My actual appointment with the oncologist was fine -- it always is. He likes that I'm an "easy patient," meaning I don't force him to make difficult treatment decisions. He's still very impressed that I have gotten almost 13 years of Progression Free Survival out of 6 rounds of Rituxan. My physical exam was fine, and my blood work looks good. 

Other than that, we talked about my kids and what they are up to, my travel plans for next year, my dermatologist appointment, my colonoscopy, and a few other unimportant things, the kind of things that people talk about when they only see each other every six months. 

It was a good appointment.

And more importantly, it was a reminder that I'm still a cancer patient, even if I haven't had treatment for a while. That's a good thing. I don't think I want to forget how that feels. As long as I'm a cancer advocate, I want to keep that connection. It's all much too big a part of my life to just let go. 

ASH commentary is coming soon.

Giving Thanks

I've been looking at the ASH abstracts, and started a few posts on interesting topics, but I'm still working on them. I thought I'd pause today for Thanksgiving.

I know that not everyone reading is from the U.S., so: Today is Thanksgiving, our annual holiday where we pause and remember good things in our lives and give thanks for them. (There's also lots of eating, since this holiday is supposed to have started as a kind of harvest festival.)

I think cancer patients (especially those of us with Follicular Lymphoma) have a hard time with Thanksgiving. On the one hand, we're alive, and that's certainly something to be thankful for. On the other hand, we're often living with difficult things, whether the physical problems from the FL itself, or side effects from treatment, or the emotional burden of watching and waiting, or just worrying about a successfully-treated cancer that might come back. Nothing is easy with this cancer.

But, hopefully, there is more to be thankful for than not. 

This is my 14th Thanksgiving as a cancer patient. As I sometimes do, I looked back at what I wrote in this blog about what I was thankful for that first year (2008). I'll tell you something that I find kind of 'amazing -- thinking about it over the last few days, my list this year is pretty much the same list, 14 years later.

I'm still thankful for all of the wonderful doctors I've worked with. I counted 11 of them back then, based on the business cards in my wallet. I've added a few since then, as I deal with an aging body and more that has gone wrong with it. They're all great. All things considered, I'm a reasonably healthy 55 year old with an incurable cancer who can still more or less do what I want to do. I know not everyone can say that. I give doctors at least a little bit of credit for that.

And I'm very thankful still for FL researchers. I certainly write a lot of about their work. What's different now, 14 years later, is that I've actually gotten to meet some of them and work with them. That's been very cool. They're passionate about what they do, and they do it very well. 

I'm still thankful for my job, which gives me great security in many ways. I don't talk much here about the work that I get paid for. I'm a teacher, and I teach writing. It's a very fulfilling job. I like my students and I like my colleagues. I've been doing in for over 30 years, and it's still feels like something new all the time. There's a lot to be thankful for there. 

OK, I guess I'm still thankful for music, though I gave up my music "career" long ago. But I do still get to listen to my kids play. My oldest plays saxophone in a band, and we may get to see them play Saturday night (if we can stay up that late). My middle child has taught himself to play banjo. As I said 14 years ago, my wife and I always wanted a house full of music. We still have one.

I said back in 2008 that I'm thankful for my support group. I rely on them less now than I did then, but I will say that I am thankful for other FL patients who have shared their stories with me, including many of you reading this. Even 14 years after diagnosis, it's always comforting to hear from someone who has experienced the same thing as you. Cancer can be lonely in many ways, and talking to some of you can make it feel less lonely.

I said back then that I was thankful for my parents, and that's true. They were so wonderfully supportive. "Were," unfortunately. Both have passed on, and I lost both to cancer. It was another of those strange things, to be able to share cancer stories with your parents -- something to be thankful for, and not thankful for. I was lucky enough to have had a good relationship with both of them for my entire life, even during those years when most people don't have great relationships with them. I miss them, especially at this time of year.

And I'm still thankful for my brother. I said back then that my cancer had brought us closer together, and losing our parents brought us a little closer, too. I'm very thankful of all of the work he has done to raise money for cancer research.

And I'm still thankful for my kids, and not just because of the music. They are all technically adults now, though they're still just kids to me. But they've grown into wonderful people, who care about others and want to make the world a better place. I can't ask for more than that. My oldest is here for the holiday from his job about 300 miles away, and my middle one just took a job in the state that we live in, so we're seeing him more often. And our youngest can't be with us for Thanksgiving, since they're literally halfway around the world, studying in Japan. It's a wonderful opportunity that I am very thankful they were able to experience. I'm a happy dad, and 14 years ago, I'm wasn't sure I'd be here to see it all.

And I'm mostly thankful for my wife, Isabel. I like what I said so long ago, so I'm going to repeat it here:

And I'm mostly thankful for Isabel. She had no idea what she was getting into when she promised that whole "sickness and health" thing -- no one ever does. She 's been so strong, so positive, so supportive through all of this. I heard someone say once that in a good marriage, you take turns being crazy. We've managed to do that, balancing each other out, being positive when the other is feeling bad, energetic when the other is tired, sane when the other is crazy. It's a great comfort to know when I'm down, she'll be up. Love you.

We'll be celebrating our 30th anniversary in a less than 2 months. I couldn't be more thankful for anything in my life.

Happy Thanksgiving, everyone. 

 

More on Watching and Waiting

I got some really interesting comments on my last post about watching and waiting. I started to respond to them in the comments, but I thought it might be easier to respond to them here in a new post.

Just as a reminder: I was diagnosed with Follicular Lymphoma in January 2008, stage 3, grade 1 and 2. Various tests at the time suggested I could watch and wait, and after a month, I had another scan, which confirmed that things weren't growing very quickly. My oncologist recommended I watch and wait. His reasoning was, at least back then, there were not a lot of treatments available. Since this disease is considered incurable, the thinking back then was that it was better to hold off on treatment if you could, since you would probably need a bunch of them, since the disease would keep coming back. 

None of that happened to me. I watched and waited for two years to the day, starting Rituxan on the two year anniversary of my diagnosis. I haven't needed treatment since. I think we know more about FL now, and there isn't the assumption anymore that we'll all be on that same path -- needing multiple treatments, with the time between treatments getting shorter, and the disease getting more aggressive each time it comes back. That does happen with some FL patients, but with more and better treatment options, many of us have more time between treatments, and there isn't a definite pattern of having the disease become more aggressive and resistant to treatment over time. 

Even though I went through watching and waiting based on some old assumptions, I still don't regret the choice. It worked for me, and I' do it again, even with all of this new knowledge.

Now, on to the comments. 

A couple of readers shared that they are now watching and waiting -- one for 2 months, and one for 11 years. It's fascinating to me that there can be such different experiences with the same disease. 

One of those readers (they both posted anonymously, which is fine, but it means I can't address them by name) said "Thank you for this. I was diagnosed with 'Follicular Lymphoma' 2 months ago & am in the Watch & Wait phase. Will show this study to my oncologist & possibly start maintenance therapy. Honestly, I have no desire to undergo any therapy, so I was okay with Watch & Wait. But as it stands, I would get a greater benefit from starting retuximab & maintenance therapy sooner."

Let me remind everyone first that I am not a doctor, so my medical opinion means about as much as an overly friendly guy sitting on a bar stool next to you. I do think that studies like this provide data that can help us make decisions, but it's also important to remember that when a study discusses statistics, they are always the median of a group -- in other words, the exact middle, so exactly half of the people in the study did more or better (of whatever is being studied) than the median, and the other half did less or worse. There's never any guarantee that you'll get the same result (in fact, "median" means the chances are 50/50 that you'll get the same result). Statistics aren't destiny. If you really have no desire to start therapy, and there's no physical reason to, then watching and waiting some more is still an option. I think it's smart to talk to the oncologist about it. Ask lots of questions and make sure you're satisfied with the answers. And let us know what you decide. 

And since you're just two months into this life, I'll say to you what so many said to me almost 15 years ago: I'm sorry you had to hear those words on the day you were diagnosed, but I'm glad you found us. Good luck with the chat with the doctor.

The other (11 year) watch-and-waiter pointed out that Covid has affected their choice, and they are happy to stay on watch and wait until things have calmed down some more. This makes sense -- treatments for FL will all lower our immunity to some extent, and lower immunity is not what we want during a viral pandemic. So that's probably a good choice -- if it's been working for that long, stay with it until there's reason to stop.

(That's the kind of wisdom that 11 years of watching and waiting will bring. It takes some real self-knowledge to live that long while knowing you have cancer. That's awesome.)

Another anonymous reader asked, "Is there actually a reason why maintenance therapy with rituximab is stopped after 2 years? What would be an argument against maintaining a maintenance therapy as long as the patient tolerates it and possibly keeps the tumor burden within limits?"

Excellent question, and there is a good answer. Simply put, Maintenance lowers immunity and increases the chances of getting a serious infection. There was a report at ASH about this in 2018. Researchers split FL patients into two groups after they had four rounds of Rituxan and had a response from it. One group had Rituxan Maintenance for 6 months, and the other had it for 5 years, They found no major differences between the two groups  in their Event-Free Survival, Progression-Free Survival, or Overall Survival. In other words, more Rituxan didn't make them live longer or keep their disease away any longer. This was true even after 10 years of observing the two groups. But there was a difference in the problems it caused. Rituxan goes after cells with the CD20 protein on their surface, meaning the B Cells that turn cancerous in FL. But it also goes after healthy B Cells, not just the cancerous ones. And B Cells are an immune cell. So 5 years of wiping out healthy immune cells means greater risk of infections, but with no benefit. Two years seems to be the right balance between effectiveness and safety. 

Finally, reader Liz did what I requested, and found the original research that the ASH study was referring to. I had said that this year's ASH abstract mentioned Quality of Life but didn't get into any detail about how the measured Q of L. Liz found the details for us. You can find a link in Liz's comment from my last post, in case you want to read the details. But basically, as Liz points out, the study shows that FL patients undergoing maintenance were less worried than those watching and waiting. 

However, as Liz says, "I think its relevant to note that baseline scores were generally high but equally important there was no significant deterioration in physical or functional wellbeing scores within the treatment arms. I think having looked through all this, that it's so important to have informed conversations with our doctors about our individual treatment priorities and concerns. Watch and wait is still an appropriate choice for many but moving to treatment earlier does have potential benefits and may just be worth a more detailed initial discussion at diagnosis. I'm not quite clear why some of us aren't given that opportunity for discussion."

And that's really what this is all about -- watch and wait is one option, but there are a bunch of others. And as much as I'm happy to give you my opinion, and as much as data from great studies can give you things to think about, the best person to talk to is you doctor. Hopefully, they can help you think through all of it -- the best treatments available, your psychological and emotional needs, your goals (going for a long time between treatments? Ok with something more aggressive?), and anything else that might affect your choice.

And Liz, 6 months into watching and waiting, good luck to you, too. Keep us updated.

And good luck to all of you who are watching-and-waiting. I know it's not easy. But it does get easier with time, and as I said last time, I think it does ultimately make us stronger.

Thanks for the comments everyone. Stay well.

More ASH soon.

 

ASH Preview: Watch and Wait vs Rituxan

I'm getting into the ASH abstracts now (all 282 of the Follicular Lymphoma ones), and there's actually a lot to think about. I'm finding the usual mix that I have found in the last few years -- lots of deeper looks into what we already know, some newer treatments (lots of combinations of new and old treatments), but no real blockbusters that I can see on first glance. 

This first preview post is one of those "deeper dives into what we already know." It's a long-term follow-up of a study that compares Watching and Waiting to Rituxan in asymptomatic FL patients. As someone who watched and waited for two full years, and the had just Rituxan as a treatment, I am very interested in this study.

The presentation is called "607 Long Term Follow-up of International Randomised Phase 3 Study of Rituximab Versus a Watch and Wait Approach for Patients with Asymptomatic, Low Tumour Burden Follicular Lymphoma Shows Rituximab Is Highly Effective at Delaying Time to New Treatment without Detrimental Impact Following Next Line of Therapy."

As the title indicates, this study involved 463 FL patients in the UK, Australia, New Zealand, Turkey, and Poland. They were divided into three groups: one group watched and waited, another was given just Rituxan, and the third had Rituxan + Rituxan Maintenance.

This research has been reported on before (the first patients in it were enrolled in 2004, even before I was diagnosed). Its purpose was to compare how well the three different approaches worked on patients who were a lot like me (and probably some of you)-- no symptoms, not a lot of large nodes, and didn't necessarily need treatment right away. The early results of the study found that after about 4 years, 88% of those in the maintenance group had not had a new treatment, and a similar number for the Rituxan-only group (compared to only 46% of the watch-and-waiters). However, there was no difference in Overall Survival for all 3 groups (which is kind of typical for FL treatments, no matter which ones they are comparing). 

The researchers also report that "Selected [Quality of Life] measures were shown to be superior for patients in the RM arm compared to W&W." This is only a summary of the research, so they don't get into any more detail, but I'm very curious to know what they measured for Q of L. I'm guessing they were emotional issues, maybe? Getting some kind of treatment eases the emotional burden of watching and waiting? (Though it's also interesting that they "selected" Q of L measures. Maintenance can also lower immunity, since B cells are being targeted for a long period of time. maybe that wasn't considered a Quality of Life issue?)

Anyway, this presentation at ASH is a long-term follow up of the same patients -- a median of 12.3 years.

Researchers found that 242 of the patients from the study had needed a new treatment over that time -- 133 in the WW group, 42 in the Rituxan group, and 67 in the maintenance group. The median time that it took for a second treatment was 2.7 years for the watch-and-waiters, 9.9 years for the Rituxan group, and longer than that for the maintenance group (they had not reached the median, meaning less than half had needed a second treatment). After 10 years, 28.8% of watch-and-waiters had not needed a second treatment, compared to 49.4% in the Rituxan group and 64.5% in the maintenance group.

The median was not reached for any of the three groups for a next treatment after that first one.

Some of the other results from the study:

The 4 year progression-free survival for both Rituxan groups was better than for the W and W group.

There was no significance difference for Overall Survival between the three groups.

There was no significant difference in the time to transformation between the three groups.

There was no significant difference in rates of developing a new cancer between the three groups.

It's all a very interesting bit of research, and confirms a lot of what was found out years before. that's what is so interesting to me. Looking at the numbers, there seems to be a lot of evidence to show that watching and waiting isn't worth it, and some kind of Rituxan (with or without maintenance) is a better choice. And yet, we still have lots of people who are watching and waiting.

I think "choice" is the key word here. As I said above, the whole idea of "Quality of Life" has me wanting to hear more. How are they measuring it? Which "selected" qualities did they focus on? (If anyone in the class wants to do a research project for extra credit, feel free to take it on. Find the original research and report back to me. And yes, I am a teacher.)

But thinking about Quality of Life brings up another issue for me -- the emotional benefits of watching-and-waiting. I occasionally have FL patients contact me about treatment choices that their doctor has suggested, asking my advice, especially about watching and waiting. After I remind them that I am not a doctor, I tell them why W and W was a good choice for me, and I remind them that it's not a permanent choice. In other words, you can decide to wait until there are physical symptoms that make treatment necessary (which is what happened to me). But you don't need to wait that long. You can decide after a couple of months that the emotional burden of living with an untreated cancer is just too much. Tell your doctor you changed your mind. Ask for Rituxan. Most patients I talk to don't do that. they manage to live with W and W until it's necessary.

And maybe that's why people keep watching and waiting, even if there is evidence that treating right away is a good (maybe better) choice, at least by some measures. Maybe they hold off out of fear of what kind of side effects will come with treatment.

But maybe, just maybe, it's an emotional test that we give ourselves. We want to prove that we can beat the cancer without needing to be treated right away. 

I'll have to think about that some more.

I'll keep looking at ASH abstracts and writing more soon.

 

ASH Preview

My goodness -- the ASH annual meeting is happening in just over a month.

If you're new around here, ASH is the American Society of Hematology, and every December, they have a big meeting where blood cancer researchers present their work. It's one of the two big cancer meetings that I follow every year -- ASCO in June (or so), and ASH in December.

Last week, ASH abstracts were published online. It's right about the time they are usually published, but they snuck up on me anyway. There are 282 abstracts for Follicular Lymphoma. I'll do my best to go through them and write about the ones that seem most interesting, impactful, or just fun (every now and then, someone will do research that says something like whisky is good for you).

I was reminded about ASH because I got two alerts today about ASH. The first one is from BioPharmaDive, called "Bispecific cancer drugs and gene therapy advances: What to watch at next month’s ASH meeting." The title tells you the focus of the article. Bispecifics are big this year for blood cancers. The article mentions a few studies in lymphoma for new bispecifics. Right now, they will all try to improve on Mosunetuzumab.

The other ASH preview was called, interestingly enough, "Ash 2022 preview – Affimed and Aptose score" from Evaluate. It focuses on two lymphoma treatments -- one a new version of CAR-T, and the other an NK Inhibitor. I'll read more about them later.

The treatments in the articles aren't necessarily aimed at Follicular Lymphoma, but they do inspire me to start reading some more (next week, probably, after my job eases up just a bit this weekend).

I enjoy ASH for the reason I enjoy ASCO -- even if very few of the treatments being discussed will actually make it to pharmacy or the doctor's office, they remind me that there is lots of great research out there, and lots of smart people working to improve our lives. 

More soon (I hope).

Shared Decision-Making

Interesting research from a conference on blood disorders that brings up a lot of important issues.

The conference is from an organization called SOHO (The Society of Hematologic Oncology), and it took place September 28 to October 1. I'll be honest, I'm not really familiar with SOHO, but looking at some of the research from their meeting, it seems like I should find more time to pay attention to them.  

The specific presentation that caught my eye is called "Preferences and Perceptions Regarding Treatment Decision-Making for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL)."

From the title, you can see that this isn't about Follicular Lymphoma. And if you've been reading for a while, you know that that there is a connection between FL and DLBCL. While FL is indolent and usually slow-growing, DLBCL is more aggressive and fast-growing, and some FLs can transform into DLBCL. 

But the connection I see isn't really about the type of lymphoma at all. It's about the "Perceptions Regarding Treatment Decision-Making" part of the presentation. How we decide about treatment options is an issue no matter what kind of cancer we might have.

The study looks at how patients, caregivers, and doctors feel about how much involvement all three groups have when it comes to making decisions about treatment. DLBCL is an interesting cancer to focus on because it has few options for relapsed/refractory patients -- that is, patients who have already had at least one treatment, and now need a second or third treatment because the first (or second) didn't work or stopped working after a while. 

The researchers did interviews with 30 people -- 14 DLBCL patients, 8 caregivers, and 8 oncologists. 30 people is a small study compared to something like a large phase 2 or 3 clinical trial, but doing interviews makes up for that -- the researchers can go much deeper with their questions. 

The results were really interesting to me.

About 71% of the patients and 38% of the caregivers felt like they didn't have much choice when it came to the treatment they would receive. This was usually because the doctor told them that the treatment being suggested was a well-established "standard of care." There are guidelines from the NCCN for each type of cancer that make suggestions, based on the most current research, on what treatments should be given whenever a treatment is needed. Another reason, though, was the shock from diagnosis, which made it hard for them to think clearly about what to do.

Interestingly, all of the doctors in the study felt that the limited options available from R/R DLBCL made it hard to integrate patient and caregiver choice into the decision. However, all 8 of the doctors also felt that it was important to include patients in the decisions, but 5 of the 8 also thought that lack of patient understanding made it hard to include them in the decision.

Some other issues that came up (though this doesn't cover al of them):

5 of the 16 patients thought that the doctor had over-emphasized how effective the first treatment would be, so they were unprepared for the return of the cancer.

71% of the patients felt satisfied with their treatment, though 3 patients felt overwhelmed with details, and felt that what they had first been told about treatment ended up not being true, or their treatment plan changed and the change wasn't communicated well. Also, 4 patients felt their doctor wasn't prepared to help them with issues like mental health, and 2 patients thought their doctors didn't know about treatments beyond the standard of care and couldn't make other recommendations.

Now, some of these issues have to do with DLBCL, like there being limited options available. 

But the lessons for those of us with Follicular Lymphoma, in my opinion, are clear:

First, because we do have multiple options for R/R FL, unlike DLBCL, it's possible that we'll have more choice than the patients in this study. There is less of a standard of care for FL than there is for DLBCL -- that is, less agreement among experts on which treatment should be given first, then second, then third. We have lots of options, and the range of options can be confusing (even to some doctors, from what I have been told). It's important that we know our options.

Second, it's important to get second opinions. It's easy for many of us to get overwhelmed at diagnosis, like the patients in this study. But for many of us with FL, there is less urgency. The slow-growing nature of some Follicualr Lymphoma types means we may have weeks or months to make a decision (or even longer -- I watched and waited for 2 years). That gives us time to take a deep breath, come to terms with the diagnosis, and educate ourselves. That's not the case for every FL patient, but for those of us with the luxury of time, education about the disease is a good way to spend that time.

Third, I am very aware that not all of us have a choice. Not just because we need treatment immediately, but also because insurance or whoever pays the bills may have a strict standard-of-care plan, and patients get certain treatments in a certain order whether they like it or not. Some other patients may live in a place where there aren't many oncologists, and traveling for a second opinion just isn't an option. Choices are limited. And that's OK. Choice is great, but it's important to remember too that standard-of-care is the standard because it has the most research to back it up. You might wish that you could try a new inhibitor or a radioimmunotherapy, but R-squared is all that's offered, but that doesn';t make R-squared a bad choice at all. 

The bottom line, in my opinion (and this is a good time to remind you all that I'm not a doctor or a cancer researcher, just a patient who reads and listens a lot): Stay educated. Learn as much as you can. Be able to contribute to the choice when you have the option. And if you don't have a choice, your self-education will at least let you understand the treatment that you do receive.

That's a very good thing.

 

Lenalidomide and Secondary Cancers

Since I've been thinking and writing about secondary cancers lately, I thought I'd share this: "Second primary malignancies in patients with haematological cancers treated with lenalidomide: a systematic review and meta-analysis," published a couple of days ago in The Lancet Haematology.

I'll give you the good news up front -- Lenalidomide doesn't seem to cause secondary cancers in Follicualr Lymphoma.

Lenalidomide is also known as Revlimid, and it is the second "R" (along with Rituxan) in the combination R-Squared. This treatment is, of course, an important option for Follicular Lymphoma patients, since it is the first non-chemotherapy treatment that has been shown to be as effective and safe as traditional chemo like R-CHOP or B-R. Safety is important -- in the study that compared R-Squared to chemo, it was found that R-Squared had about the same amount of side effects, but different ones. 

One long-term side effect of any cancer treatment is the potential for developing secondary cancers -- a new cancer other than the one being treated. They happen, because many cancer treatments work by affecting the DNA of cancer cells, and sometimes normal cells, too. When a normal cell's DNA is changed, it can change in bad ways, making it hard for the cells to die a natural death, and thus become cancer cells.

So that brings us to the Lancet article.

Lenalidomide has been used for a while to treat Multiple Myeloma, another blood cancer that shares some characteristics with FL. It can grow slowly, for example. When I was a guest on the No Better Time Than the Present series (see the YouTube video here), I talked a little bit about how much I could connect with my host Yolanda's experience as a patient with Multiple Myeloma. Yolanda watched and waited for 5 years before treatment, for example, way more than my 2 years.

Whole Lenalidomide can be effective for for Multiple Myeloma, several studies have shown that it increases the the chances of secondary cancers for MM patients. But, as the researchers say, there hasn't been a careful look at whether Lenalidomide increased the chance of secondary cancers for other blood cancers and blood disorders that use it as a treatment.

So they did what's called a meta-analysis. Instead of running a brand new clinical trial, they looked back at the data from every bit of research they could find that studied Lenalidomide. They found a whole bunch -- 38 trials that included 14,058 patients, including 18 trials with patients with Multiple Myeloma.This allowed them to compare MM with other blood cancers.

The results were kind of fascinating. Patients with MM had a higher incidence of secondary cancers, both new blood cancers and new solid cancers. But patients with other blood diseases -- lymphoma, CLL, or myelodysplastic syndrome -- had no increased chance of secondary cancer. 

That's good news for us. I can only see the abstract of the article, not all of the data, so I don't know if they broke out Follicualr Lymphoma studies specifically. But I don't think that matters for the results. At least according to research that has already been published, Lenalidomide does not increase our chances of a secondary cancer. 

It's not good news for Multiple Myeloma patients, of course, and I feel for them. But I also find it fascinating that there is something about MM that mixes with the mechanisms of Lenalidomide that just isn't present in FL or other lymphomas. I'm sure lots of Lymphoma experts will find that even more fascinating, and that's great news. A new line of research that might help them understand MM a little bit more.

One less thing to worry about....

A Tool for Predicting POD24 in Follicular Lymphoma?

 Very cool research from Spain, published in Clinical Cancer Research this week, in an article called "Monitoring of circulating tumor DNA predicts response to treatment and early progression in Follicular Lymphoma: results of a prospective pilot study." It has some potential implications for POD24 patients.

Lots of background before we get to the article.

POD24 stands for "Progression of Disease within 24 month." It's the name for what happens when an FL patient receives immunochemotherapy (like R-CHOP or B-R) and has a response, but then relapses (has progression of the disease) within 24 months. Research shows that this happens to about 20% of FL patients. Research also shows that, unfortunately, POD24 patients have a lower median 5 year survival rate than other FL patients. It was a fairly big deal that researchers were able to identify this group of patients, and lots of Lymphoma experts think that the Lymphoma Research Community needs to focus its attention on helping this group. And lots of researchers have done that.

Now, a separate bunch of researchers are working on "Liquid Biopsies." I'm sure we are all familiar in some way with "solid" biopsies, where a sample of possibly cancerous cells is taken from out body. Maybe this is with a fine needle aspiration (not fun, but the least painful option now available). For others -- me included -- this meant surgery to remove a lymph node, and/or a bone marrow biopsy to get inside a bone and remove some of the inner material. (I had both of those.) "Solid" biopsies are not fun. They are invasive and painful.

(Sorry -- I probably didn't need to remind you of that.)

With a liquid biopsy, a sample of blood is taken and analyzed to see if there are any tiny cancer cells floating around. They're called "circulating tumor DNA" or ctDNA because they float around in the blood, too small to be picked up a scan, and not gathered up in a lymph node in a big enough group to justify a solid biopsy. But they are still there, in very early stages. A "liquid biopsy" can find them, early, without all the cutting.

I wrote about liquid biopsies a few months ago, looking at an article that basically laid out what we knew about them so far, and how promising they were.

So bring those two things together now: some researchers in Spain have done a prospective study that uses liquid biopsies to find circulating tumor DNA to predict POD24. This is excellent news.

The researchers looked at samples of plasma (the liquid part of the blood) from 36 patients with Follicular Lymphoma. The patients came before, during, and after treatment (they had immunochemotherapy). Then they followed the patients for a median of about 3.5 years. The goal was to see which of the patients turned out to be POD24, and to then look at the plasma samples to see if there was any ctDNA in the samples, and whether that could have predicted the POD24.

What they found was that, yes indeed, the liquid biopsies could find the ctDNA and could predict that some patients would relapse early. There was a clear difference in the samples of POD24 patients and patients who did not have a Complete Response to treatment, compared to non-POD24 patients and those who did achieve a CR.

From this, they think their method for identifying ctDNA could be used during clinical trials to monitor patients, and could one day be used in clinical settings, allowing FL patients to monitor their status with a blood test, rather than a scan (or a solid biopsy).

Of course, the important words in the title are "prospective pilot study." This was a small sample of patients, not in an "official" trial setting. So it shows a lot of promise, but it's not something you're going to see in the doctor's office anytime soon.

I do think its important, though, to recognize that researchers are becoming more and more conscious of not only the importance of dealing with POD24, but also of just paying attention to Quality of Life for all of us.Liquid biopsies won't cure anything, but they will make the experience of living with FL a  little bit less unpleasant. And that's worth a lot.

Cancer Vaccine by 2030?

Earlier this week, I saw a whole bunch of news stories about a possible cancer vaccine being available by 2030. I'm skeptical. (But that's just how I am.)

I'm actually less skeptical the more I think about it.

The vaccine possibility came during an interview with Dr. Ozlem Tureci and Dr. Ugur Sahin, the married researchers who founded BioNTech, the company that created an mRNA Covid-19 vaccine with Pfizer.  

I'm skeptical because I'm always skeptical by anyone who claims they might find "a cure for cancer," as if cancer were one disease. It's certainly not -- even Non-Hodgkin's Lymphoma isn't a single disease, and has up to 80 subtypes. And even within a single type of cancer, the pathways that cancer cells use to stay alive, and the microenvironment factors that they take advantage of to grow -- it's all just mind-blowing to think about. Cancer cells find a way to avoid treatment, to come back from treatment, and to find new ways around treatment. Finding one way to stop a cancer cell is a very difficult task. Finding one way to stop ALL cancer cells, no matter the type, just seems impossible. 

And yet....

Apparently, Drs. Tureci and Sahin were originally working on an individualized cancer vaccine when their mRNA technology was needed for Covid. Now they're back to the cancer vaccine.

It is individualized, something like CAR-T. As they describe it, after surgery to remove a tumor, the patient would receive a vaccine that recognizes the cancer cells. It uses T cells (like CAR-T) to scan the body for cancer cells and eliminate them. Like CAR-T, in theory, the T cells will have a memory so that if the cancer cells come around again, the T cells will find them.

It's an interesting concept, and to me, the fact that it is individualized is what makes me slightly less skeptical than I would be about some other "cures for cancer."

And, of course, it's important to go beyond the headline and look a little closer. Lots of stories have "cure" in their headline to catch people's attention, but a quote from the interview is important:

"Yes, we feel that a cure for cancer, or to changing cancer patients' lives, is in our grasp," said Professor Ozlem Tureci during an interview on BBC's "Sunday with Laura Kuenssberg."

A cure for cancer OR changing cancer patients' lives? That leaves open some possibilities. A treatment that knocks back a previously incurable cancer will "change cancer patients' lives." So will a treatment that doesn't cure it, but does control it to the point where it becomes a chronic disease. So will a treatment that greatly extends a patient's life after a disease becomes refractory, extending survival for years instead of months, which is often the case now.

So I remain skeptical of any treatment that claims to be a cure for cancer -- or skeptical of any headline that makes that claim. Especially a treatment that's essentially an idea. I'll be less skeptical when it's tested in a lab, and then in a phase 1 trial, and a phase 2 trial -- you understand what I mean.

But that doesn't mean I won't be keeping an eye on this. 

(It also means I fully expect to be around in 8 years to see if they were right. Expect a blog post either way. I have a good memory for these things.)

 

 

New (Expanded) CAR-T Trial

Early results from a new trial for a CAR-T treatment look very promising. It's not actually a new trial, but an expanded one. Still, the results are promising and worth keeping a close eye on.

The treatment is called MB-106, and is manufactured by a company called Mustang Bio. The company has already been conducting a phase 1/2 clinical trial at a single location, Fred Hutch Cancer Center. I wrote about this in May, when they reported results at the European Hematology Association meeting. 

This CAR-T treatment is different from those already available. It targets CD20, the same protein that is found on B Lymphocytes that is the target for many other B Cell Lymphoma treatments (like Rituxan). That is important because it means that patients who tried other CAR-T treatments, which target CD19, may be able to use this one as a next-line treatment. (That's one of the things the clinical trial is testing.)

The early trial of just 12 patients at Fred Hutch found that 11 patients had a response. There were 9 patients with Follicular Lymphoma, and 6 of them had a Complete Response. Side effects were great --  none of the patients had serious Cytokine Release Syndrome, and none had ICAN (a type of nerve damage that is common in CAR-T treatments). Four patients have had a Complete Response that lasted for more than 24 months, with the CR lasting 33 months (and still going, as far as I can tell).

The results were good enough to expand the trial. It is still a phase 1/2 trial, but now it will happen at 6 different cancer centers, and involve up to 287 patients. The patients will be put into 3 groups: one for patients with aggressive lymphoma (including transformed FL), one for patients with indolent or slow-growing lymphoma (including other types of FL), and one for patients with CLL. As a phase 1 trial, one of the goals is "dose escalation," or figuring out how much of the treatment to give a patient that will be most effective while creating the most manageable side effects. Once that is figured out, they will add more patients to each of the three groups.

The treatment is in the news this week because the company announced the early results from the first patient enrolled in the expanded trial. The patient did not experience cytokine release syndrome or ICANS, much like many of the patients from the earlier version of the trial.

It will be very interesting to see more results from this trial. Perhaps there will be more data presented in a couple of months at ASH, and definitely next spring at ASCO.

All of this is just more proof that CAR-T is going to be an important part of our treatment lives in the future. We're at the point where new CAR-Ts are not only going after different targets on cells, but are being developed so previous CAR-T patients can try a different version. That tells me that CAR-T is an established part of the treatment landscape for us.

Lots of questions still to be answered about CAR-T. Can someone develop an allogeneic or "off the shelf" version that will be as safe and effective, but won't require a specific treatment made for each individual patient? In the meantime, are there other ways to keep costs down? Can new developments figure out how to make CAR-T effective for that 20-30% that don't get a response at all? 

Stay tuned. I;m sure there be lots more CAR-T research to report in a couple of months as ASH approaches.

CAR-T Animation

The Peter MacCallum Cancer Centre in Melbourne, Australia (known as Peter Mac) has posted a very, very cool video. It shows how CAR-T works by showing the Killer T-Cells identifying abnormal (cancer) cells, connecting to them, and then signaling that the T cells should eliminate the cancer cell. It is extremely interesting.

The video, which won the "Best of Show" for both the Science and the Health categories at the Doctors Without Borders Film Festival, was created by  Dr. Maja Divjak from Peter Mac.

The video is about 11 minutes long, and it can be found embedded in a story on the Peter Mac website. The video is also available on YouTube, where it might be have more helpful tools for those of you who need translation help.

I really enjoy videos like this. For the most part, I can picture the kinds of processes that are involved with cancer treatments. And while I do my best to describe them in simple terms, a picture is certainly more helpful in allowing people to see what is happening. 

Maybe it's not really helpful in a lot of ways. Maybe seeing an immune cell find and eliminate a cancer cell doesn't help make the treatment any more effective. But to me, emotionally, it's great to see a treatment doing its job. It makes it seem more real. And for those of us with Follicular Lymphoma, a cancer with no easy answers and a lot of waiting around, seeing something that seems more concrete and real.

I hope you enjoy the video.

 

 

Secondary Cancers: A Reminder

In August, I wrote about secondary cancers in Follicular Lymphoma. It's worth bringing up again.

Last week, I had a growth removed from my forehead. The biopsy came back negative -- pre-cancerous. Not yet cancerous. But it could have been if I had let it go longer.

As I wrote in that post, Follicular Lymphoma patients are at higher risk for developing a secondary cancer -- a new cancer besides the FL. That's true for lots of reasons, including having "imperfect" immune systems due to our B-cell cancers, and sometimes because of treatments we receive, which can cause changes to our DNA that can get out of hand. It's good to be aware of that, and do all of the kinds of screenings that are recommended. I had a colonoscopy earlier in the year, ten years after my first one. The doc found a benign polyp -- no problem, but now I'll do the next one in 7 years, just to be sure.

And I see my dermatologist at least once a year, more often if I have a concern. My oncologist has been especially insistent about this, and I'm glad of it. I've had some weird skin patches removed over the last few years. The doctor says, "Oh that's a fliggamujangaping, nothing to worry about" as she freezes it off. I don't remember the names of the things. If she doesn't say "cancer," I pretty much stop listening and let her do her thing.

But this time, she came into the exam room and looked at my forehead and immediately said "I want a biopsy." The nurse prepared one as the doctor looked over the rest of my body, even the bottom of my feet, and said, "It all looks fine. Except that spot on your forehead. It could be squamous cell carcinoma. If it is, we caught it early. If it isn't, it's pre-cancerous, and we caught it before it became cancerous. Either way, don't worry about it."

And, strangely, I didn't worry. Maybe because I've already been through the shock of hearing "You have cancer" the first time, and it only shocks the first time. Or maybe the oncologist has been preparing me for this for a few years by telling me to get checked, so I kind of expect it every time. Or maybe I just took her at her word when she said "Don't worry." 

So this is your reminder to pay attention to potential secondary cancers. Being at higher risk doesn't mean we're guaranteed to get one. But it does mean we need to pay closer attention, and if we're concerned, to make sure we're listened to.

And if you're like me, and you can blame your Scottish/Irish/French Canadian ancestors for your fair skin and history of bad sunburns, then get your skin checked frequently. 

Take care of yourselves, everyone.

Evolving Treatment Landscape in Follicular Lymphoma

A quick one today:

OncLive has a short series of short videos (3 videos, the longest being a little over 2 minutes). they are part of a series called "Evolving Treatment Landscape in Relapsed/Refractory Follicular Lymphoma."  Three videos, featuring Dr. Krish Patel, Dr. Solly Chedid, and Dr. Madan Arora. Sometimes these are part of a longer series of videos, or previews for longer individual videos, so a few more may get posted soon. But for now, the three that are available are brief but informative.

The videos are short enough that I don't think I need to go through all of them. But the overall message is important.

We're in a time when there are more and more treatments available for us, especially those of us who have relapsed/refractory FL (that is, our last treatment didn't work, or has stopped working after a time). When I was first diagnosed almost 15 years ago, there were very few options available, and the general attitude was something like, "This disease gets more aggressive over time, so we can start with a treatment that will give maximum response time, like R-CHOP. Then we can expect shorter response times with each treatment, with side effects piling up as the treatments get more aggressive as well."

It's amazing what we've learned about FL in 15 years, and how treatments have changed (especially in developing non-chemotherapy treatments that are more targeted at the cancer cells). That means the overall approach has changed, too. Lots of old assumptions are gone, including 1) FL patients will only have an 8-10 year median survival, 2) that the disease will become more aggressive over time, 3) that chemo is the least aggressive approach, and 4) quality of life doesn't matter. The videos in the series make that clear. In theory, FL patients can live long lives (18-20 years is now the consensus for the median survival rate for FL patients), and with decent quality. 

I've said this before, but it's been a while, so worth repeating for those of you who are new to the blog:

A few years ago, someone in a support group said that her oncologist told her, "If we can keep a Follicular Lymphoma patient alive for 5 years, we can keep them alive for 50 years."

That was a long time ago, before CART-T and R-squared and Bi-specifics. It's an important point, and one that I remind myself of a lot: we have more and better treatments now than we ever did, and more options when we need them, especially if our disease is indolent enough to get past those first few years. Obviously, that doesn't apply to every individual patient, but it's enough to give me hope.

Stay well, everyone.

 

Talking to Other Cancer Patients and Survivors

The website Blood-Cancer.com (for which I have written in the past, before I got too busy) had a really nice couple of articles over the past few weeks. The articles featured two of its writers, Ramae and Deb, who had been chatting for a couple of years online. Each of them is a blood cancer patient/survivor. They finally got a chance to meet one another in person. They each wrote about it separately. Ramae's story is here, and Deb's is here.

The stories came at an interesting time for me. Last week, I had the chance to speak to some other lymphoma patients/survivors. 

I keep using that "patient/survivor" thing because I don't what peoples' status is. There's whole other conversation to be had about what we call ourselves. But that's kind of part of what I want to write about.

I don't think I've ever met any of you in person, face-to-face, but I did have the pleasure of Zooming with a few of you during the pandemic, and I've had some email conversations with a whole bunch of you.

And I really enjoy making those connections. Especially with other patients/survivors.

There's something kind of oddly wonderful about hearing someone else's story. Their diagnosis, their treatment, their survival. So many of the details are different. The people I talked to last week all had more aggressive cancers. They all seemed much younger. Their diagnosis had happened much more recently. 

But so many of the details were the same. And all of the feelings were, too. The fear. The surprise and disbelief. Confusion. Guilt. Just not-knowing. 

I remember a few years ago hearing a cancer survivor talk about what it was like to tell her kids about her diagnosis. It brought back so many feelings for me of telling my own kids. It was actually painful to hear her story. But at the same time, so comforting. It's a strange feeling, a kind of reverse schadenfreude. Not taking pleasure in someone else pain, but taking pleasure in sharing that pain.

I remember, too, many years ago, hugging someone I worked with, who had been dealing with breast cancer. It was a wordless hug. We both just knew what we should be saying, and we didn't have to, because we both knew. 

I'm not saying I feel that way with every cancer patient/survivor I meet. Some experiences really are just too different. I sometimes feel strange describing my experience to someone who has had an aggressive cancer, because there are things they've been through that I haven't. 

And sometimes the words we use just don't match up. I call myself a cancer patient most of the time. I'm not cured, and I still see my oncologist twice a year. For me, it's an active disease. But sometimes I call myself a survivor, because it's what people are used to hearing. I know for some people, it means that my cancer experience is over, and we don't have to talk about it. And that's OK. I call myself a survivor to make other people comfortable sometimes. 

But despite those differences, it seems like the similarities are greater, and our experience is distilled into one common thing - we've heard a doctor tell "You have cancer," and we've felt everythig that goes with it. 

I'm not recommending that you seek out other cancer patients/survivors to talk to, unless you know they are willing to share. But if they are, it can be a wonderful thing. It just feels less isolating. 

If you've never been a part of a support group, and it feels like you need to make a connection, I highly recommend them. In-person or online -- either can work.

And, of course, I'm always happy to listen if that's what you need.

 

 

Plant-Based Diets, Keto Diets, and Cancer

Here's some Lympho Bob trivia for you: 

The fourth most-read article on this blog is "Keto Diet and Lymphoma Treatment" from July 9, 2018.

(If you're curious what the most read article is, it's a kind of boring one from April 2021 in which I report on an oncologist's appointment and show you the Peace Garden at the cancer center that  go to. The top 3 all include photographs, which is something I don't usually do, but maybe I should start.)

I'm bringing this up because I want to report on an article from JAMA Oncology that looks at diet and how it affects cancer. It's not specifically about Follicular Lymphoma. It's not even reporting on original research. Instead, it looks back at a whole bunch of other studies that try to show if there is a relationship between diet and cancer. In particular, it looks at the research around two popular diets -- Keto diets and plant-based diets. I know that post about keto diets got a lot of hits, so it caught my eye. It actually came out about two months ago, but I've been waiting to write about it until I could read it carefully and think about it.

It's not surprising that this would be a popular topic. Based only on what I see in the online cancer discussion groups that I belong to, people are very interested in how the things that they eat might have an effect on their cancer -- especially whether or not their cancer can be cured through diet alone.

And we all know people who have had their lives legitimately changed by changing the food they eat. And there are plenty of people who profit off of those changes, making claims that certain diets, or even certain individual foods, will solve all kinds of problems. In my nearly 15 years of living with cancer, I've seen a whole bunch of people telling me to try certain foods, diets, and supplements -- or to avoid certain foods, diets, and supplements -- to cure my cancer. And they almost always include a statement like "They've done studies!" without telling me who "they" are or where I can find the particular studies. 

And when they do have an actual study, it's not a clinical trial, but instead something isolated in a test tube or petri dish, or tested on animals but not humans. 

The truth is, there is no solid scientific evidence that any food, or any diet, will cure your cancer after you've been diagnosed. That's one of the conclusions from the article. 

I certainly understand the desire to want to find an easy solution to a cancer diagnosis, especially a solution that allows us to do something. So much of being a cancer patient just seems to be sitting around waiting, even if we're not actually officially "watching and waiting." Taking control of at least one aspect of our lives and doing something to cure ourselves without drugs would be a wonderful thing. I remember reading Lance Armstrong's autobiography very soon after I was diagnosed. A few things are kind of burned into my memory. One is of him reading that a substance in broccoli might help control cancer, and his mom making him large heaping bowls of steamed broccoli every day. that sounded good to me. But it was ultimately chemotherapy that saved his life.

So if there are no studies that show that a keto diet or a plant-based diet will cure cancer, then is there any value in them?

Again, looking at the research that has been done, the answer is yes, there is some value.

Interestingly, that article from 2018 showed that a keto diet might help PI3K inhibitors be more effective. The keto diet cuts down on sugar, and that lack of sugar helps the inhibitor do its work. But that's very different from saying cutting down on sugar (a popular "cure" suggestion) will help. Cancer needs sugar to survive, so eliminating sugar will kill the cancer, right? But no. Unfortunately, our amazing bodies find ways to create glucose (sugar) all on their own. Our brains are very heavy users of sugar as well, and they manage to function just fine on a low-sugar diet. There are no easy answers, I'm afraid.

What the review of research found was that both keto and plant-based diets, while being almost complete opposites, both can result in some very good things that can help with cancer prevention --  weight loss, decreased inflammation, and decreased insulin levels.Again, that's a very different thing from saying it will cure cancer after it has been diagnosed.

And that's no small thing, even for those of us who have already been diagnosed with cancer. As we know, we are at a higher risk for developing secondary cancers. Following a diet that cuts that risk, and the risk of other health problems, is a very good thing. We'd all like to be around for a very long time. If we're looking for something to control, diet is a good way of doing that.

Interestingly, the review of research does compare the two diets and how well they may help to prevent cancer. The researchers come down on the side of a plant-based diet here: "Currently available data support plant-based diets as opposed to [keto diets] as part of a lifestyle associated with reduced cancer risk. In the postdiagnosis setting, there are currently no rigorously tested approaches that support the recommendation of any diet to treat cancer." Eat more fruits and vegetables and less meat and fat if your goal is to prevent cancer.

One of the problems with trying to figure out how diet affects cancer is that it's just a really hard thing to isolate. In other words, in a clinical trial, researchers can gather a group of people with a certain cancer and give them a particular treatment and test how well it worked. That's a lot harder to do with food. Most research is self-reported -- people tell the researchers what they have eaten. But because eating is something we do every day, it's very hard to convince a large group of people to be isolated for weeks or months to control what they eat. Even cancer patients have lives to live. People in clinical trials for, say, a monoclonal antibody go about their lives in between treatments. That's almost impossible to do with testing food as a treatment. As humans, we eat throughout much of the day, every day.

So one of the recommendations that the researchers make is that we do just that -- treat diet as a treatment to be tested rigorously, maybe by requiring patients to eat only food that is sent to them through a delivery service, for example.

And that's important to note. The researchers who wrote this article are not closing the door here, and saying food will never be a cancer treatment. Instead, they're saying that we need to do a better job of finding out whether or not it is. As different as they are, keto diets and plant-based diets do have benefits, and might have even more, if we can figure out how to measure them in a more rigorous way.

For now, the best advice is to continue to eat well, however you define that. A good diet won't cure us, but it can help prevent other health issues, can keep our bodies strong for when we need them to be (whether it's cancer-related or not), and maybe most importantly, can help us feel a little more in control than cancer makes us feel.

Also, I'm including a photo, because apparently that gets more readers.

Stay well.