Reasons for Hope to End the Year

This is going to be my last post for 2019.

It's that busy time of year, with lots of holidays, and all of the busy things that go with all of that.

I've been collecting a bunch of Follicular Lymphoma-related news, and trying to to figure out when I'll have time to post about it all.

But then I decided, why not just do a quick review of it? A lot of it is stuff that might need more explaining in the future, so maybe it's not worth going into detail right now.

In the last couple of weeks, here's some of what has happened in the Follicular Lymphoma world:

• FDA approval was sought for Tazemetostat for patients with relapsed or refractory FL. Tazemetostat is an EZH2 inhibitor, and stops the gene EZH2 from keeping a cell from dying. (Much more complex than that, but that's all you get for now.)
• The European Commission approved R-Squared (Revlimid + Rituxan) for previously treated Follicular Lymphoma patients.
• A third possible version of CAR-T has been submitted to the FDA for patients with aggressive lymphomas, including grade 3B FL.
• Another Rituxan biosimilar is under review with the FDA. (Biosimilars might be able to do the same job as Rituxan but for a lower cost.)

That's a lot of good stuff in just a couple of weeks. And I'm leaving out all of the stories that are still coming out of the ASH conference.

Maybe it's just that it's the end of the year, and everyone is trying to finish things up before they take off for the holidays?

Maybe it's an ASH thing, and all of these folks got a good response at the conference and now they're ready to make some announcements?

Or maybe some other reason?

Whatever it is, I think it's a great way to end this year, and begin the next one:

There's a lot to be hopeful for.

There is no "good" cancer, and I hate it as much as most of us when someone suggests that FL is a good cancer to have. But I will admit that, in any ways, many of us are luckier than others. If our FL is slow-growing enough,  we may have some time to see these promising new treatments actually show up at the doctor's office. There are still lots of potential problems for the ones that are still seeking approval. But even if some of those things happen, it's still great news for us.

And if you're not of a mind to think in those terms, that's OK, too. We still have lots of great things already approved. Lots of options and lots to be hopeful for.

So let's end this year off, and begin the next one, with hope.

I look forward to sharing it all with you.

Peace on Earth, and Within You

It's becoming kind of annual tradition, I guess. At this time of year, I keep seeing the message "Peace on Earth," which is tied to Christmas, and is a very good thing. And it always makes me think about Peace within as well. It's something we all need as cancer patients, and maybe even just a little more as Follicular Lymphoma patients. But we al need some Peace, whether we are patients of some kind or other, or not.

And as I usually say, today is Christmas, celebrated by many people around the world, and I'm sure by many readers. Probably not all. But the "Peace on Earth" message -- and my wish for Peace within each of us -- applies for everyone, no matter what you believe.

When I think of that phrase, "Peace on Earth," it is often followed by "And goodwill to all men." I think we probably need that part, too, if we're going to have Peace (on earth or inside us). It seems like we're too quick to be mean to others, or to just not understand them.

Last Saturday, my family and I drive up to Boston to see a show. It's a two hour drive. We parked in Harvard Square, hung out at a bookstore, had lunch at a little place that didn't have a bathroom, and then sat for a three and a half hour musical. It was delightful. After the show, we went back to the car, parked in a garage nearby. As we pulled out of the space, there was a car parked behind us, with its hazard lights flashing. Another car came along behind him and beeped for him to get out of the way. The first car moved a little, then stopped. The second car beeped again. The first car pulled up, going around a corner, and then stopped again. The second car went past, but now I was behind the stopped car. I beeped for him to pull up, since the angle I had taken when I went around the corner was too sharp, and I couldn't get passed him. He rolled down his window and stuck his hand out to wave me passed. I rolled down my window and asked him to move up since I couldn't get by. He yelled out, "The other guy in front of you could get by!" in an angry Boston accent.

I grew up in Boston. My wife says when I go back up there, I change a little. I get just a little more aggressive, especially when I'm driving. The man did pull up a few feet, and I resisted the temptation to yell out a sarcastic "Merry Christmas!" as I drove by.

It took me 15 minutes to get my blood pressure back down. But at some point on the drive home, it came to me: that guy had lost his parking ticket. He was going to have to pay a full day's price for just the few hours that he parked. He was probably angry at whoever was supposed to have hung on to that ticket. That had to be it. Why else would someone just stop in the garage and get that angry?

I was glad I suppressed my Boston and didn't say anything else to him as I drove by. He didn't need any more stress. I didn't need any more stress.

I've seen a dozen different versions of this meme online:

 I don't know who said the "real" version, and it doesn't matter. It's absolutely true.

 It's a very popular meme in the chronic illness community (which I consider Follicular Lymphoma to be a part of). Many people have "invisible illnesses." Again, those of us with FL are included (how many times have you heard "But you don't look sick"?). Whether it's a physical condition, or a mental or emotional one, whether it's a temporary problem, or a permanent one, we could al use a little kindness.  That's what leads to Peace.

But unless everybody gives a little, nobody gets any.

So that's my wish for you all this season. May others be kind to you and give you a little Peace. And may you return it to them. A little understanding of your own might bring you some Peace, too.

Enjoy your day. 

ASH Follow-Up Videos on Follicular Lymphoma

I think this will be the last of the ASH posts for this year. (Though, who knows? Maybe I'll surprise you with another one.)

Just like every year, there are lots of experts who give their opinion on the research that was presented at ASH. (Real, actual experts -- not just Cancer Nerds like me who have an informed but un-expert opinion about things.)

A lot of the commentary comes in video form. And sometimes the videos are produced during the ASH conference. A lot of times it's the researchers themselves who talk on video for a few minutes. Sometimes it's other experts talking about the research that excited them.

So here are a few videos for you that focus on research on Follicular Lymphoma at this year's ASH.

First up is "Stephen Schuster: Mosunetuzumab Leads to Durable Complete Remissions in Non-Hodgkin Lymphoma." Dr. Schuster discusses the exciting (but very early) results of research on Mosunetuzumab, the bispecific antibody that some see as a less expensive alternative to CAR-T.

Next: "Should we treat patients with high tumor burden FL with a chemo-free regimen?" In this video, Dr. Loretta Nastoupil of the MD Anderson Cancer Center discusses a phase 2 clinical trial that looked at Obinutuzumab + Lanalidomide. Basically, it's R-Squared but with a different (maybe better?) version of Rituxan. Results were very positive and an improvement (maybe?) on R-Squared.

Third is "AUGMENT: Is the combination of lenalidomide & rituximab efficacious in elderly patients with iNHL?" This one does look at R-Squared. There were a bunch of presentations about R-Squared at ASH this year (I already looked at a couple of them, but not this one.) One of the reasons people were so excited about R-Squared being approved for some types of Follicular Lymphoma is that it is an alternative to traditional chemotherapy. As a more focused treatment, R-Squared should do a better job of not killing healthy cells, and will have different (though not necessarily fewer) side effects than chemo. The AUGMENT trial has been looking at a bunch of data from its R-Squared research, and this presentation focuses on elderly FL patients.  Depending on their health, chemo can be rough on elderly patients. R-Squared, according to Dr. Marek Trněný of Charles University Hospital in Prague, elderly patients seem to tolerate R-Squared better than chemo. That's great -- a better option for a lot of patients (since most FL patients are diagnosed around age 65).

Finally, there's "When should patients with R/R NHL receive the bispecific antibody REGN1979?" The bispecific Mosunetuzumab has received most of the big news this year at ASH, but another bispecific also showed good results. REGN1979 is another bispecific (it attaches to two different cells, the cancer cell and the immune cell that  can destroy it) and has also shown some positive updated trial results. Dr. Rajat Bannerji of the Rutgers Cancer Institute of New Jersey gives the results in this video.


Lots of good stuff at ASH this year for Follicular Lymphoma patients. As I said a few weeks ago, there weren't any real blockbusters this year -- nothing that's going to change the way people are treated anytime soon. Mosunetuzumab might have that promise, but it's very early to say for sure.

But even small improvements are good for us.

ASH: Are FL Patients Being Cured?

OK, I'm finally getting to the link that Jacqeuline sent a few days ago, with a press release about an ASH presentation. Drug companies and universities send out press releases after the conference when they think they have something to brag about that cancer news sites might want to to share.

This one is certainly going to get people talking.

The presentation is called "Long-Term Follow-up of Follicular Lymphoma (FL) Patients (pts) Demonstrating Undetectable Minimal Residual Disease (MRD) Using a Next-Generation Based DNA Assay: Support for FL As a Curable Disease."

If you look again at the last line of the title, you can see why Jacqueline (and the researchers) are excited: "Support for FL As a Curable Disease."

So here's the deal. As I'm sure we all know, Follicular Lymphoma is considered an incurable disease. There are some circumstances where FL might be cured (see below), but for the most part, we're stuck with it. How the disease behaves is a different matter, and there's a wide range of behaviors: for some of us, it's really aggressive, and a patient might need treatment within a couple of years of having chemo. For others, it can grow slowly over years and years, and treatment might never be necessary. And then there are hundreds of variations in between.

But whatever little (or big) quirks our individual disease gives us, we all pretty much live with the idea that we either have active FL, or it's probably coming back at some point.

This research asks you to rethink that idea.

The study involved 60 patients. All of them had received treatment that had put them in clinical remission (meaning there were no signs of relapse in a blood test, a physical exam, etc.). The patients received a pretty wide range of  treatments -- R-CHOP, B + R, RIT, Stem cell transplant, double MAB (Rituxan plus another monoclonal antibody). There weren't any that received just Rituxan in this study (which would have been very interesting to me, as someone in that situation.)

The 60 patients had their biopsy samples looked at -- that is, the samples that were taken before they were treated -- and had the samples put through a new type of analysis that can identify changes in the genes that are related to FL. The analysis allows the researchers to identify MRD, or Minimal Residual Disease -- the changes in genes that remain even after the cells look like they're all cancer free. (See the Leonard List post for more on why MRD is becoming more important.)

After treatment, and after patients were said to be in clinical remission, another sample was taken so the FL-related genes could be analyzed again. The idea is, we have a good idea of some of the genes that get messed up when a patient has Follicular Lymphoma. Because certain genes do things like control when a cell is supposed to die, a messed up gene can keep a cell alive, and that's when you get cancer. So a test that can look at those genes can basically tell you if they're still messed up, so even if a patient seems to be in remission, the cancer might come back later (like we assume it will do with the incurable FL). Everything might be OK for now, but those genes that keep cells alive forever are still there, waiting to be jerks.

But what this test found was that some of those genes, two years after getting treatment, were back to normal. They aren't waiting around to tell the cells to stop dying at some later time. No MRD.

There were 43 patients whose samples were analyzed after treatment, and 38 of them did not show any genetic evidence of disease.

If there are no genetic mutations hanging around in the cells, can we say that these patients have been cured?

Maybe.

The researchers are optimistic, but also caution that this study involved a pretty small number of patients, and a fairly short follow-up. The lead researcher calls it an "important first step."

And it's important to be clear -- this study isn't about a new treatment that might cure FL. It's about a way of letting patients know, two years after treatment, that they don't have any evidence of disease. It's more about being able to lift that emotional weight off of us. We all learn to live with the idea that the FL will probably come back. This way of testing can maybe give patients some peace of mind.

The idea of FL being curable has always kind of floated around as a possibility. Lymphoma Superstar Dr. Bruce Cheson, who is on the team for this research, is always holding out hope that there may be a cure for FL. There is some evidence that patients with stage 1 or 2 FL might be cured with radiation. And Dr. Cheson and others sometimes talk about a "functional cure" -- a treatment can give a long enough remission that a patient dies of old age before they need another treatment (so the FL wasn't officially cured, but the patient lived a cancer-free life, so maybe that's the same thing). CAR-T and maybe some other newer treatments might be able to use the body's immune system in such a way that it can permanently fight off the disease, so even if FL is present, it's held in check.

So we may be very well be on the path to a cure.

Or at least on a path where we can live as if the FL is cured.

One final thought. If the most important thing to come out of this research is that the emotional burden of incurable disease might be lifted, I'm not sure that's going to happen.

I've talked to enough cancer patients -- people with cancers other than FL -- to know that even after years in remission, there's always that little nagging in the back of their minds that the cancer might come back. I'm not sure a test that showed no MRD would get rid of that feeling. Especially for someone ike me who has already lived with it for 12 years.

But maybe a test like this can show that there really are some patients who are being cured, and we just haven't known it yet. Maybe we can go from labeling this an incurable disease to one where we can say "some patients may be cured." So it might not help a cynical old FL patient like me, but people in the near future might have some of that emotional burden taken off of them, even just a little bit.

Even a little extra hope is a very good thing.

ASH: Mosunetuzumb (Bispecific Antibody)

Back to ASH (though, since the conference is over now, I guess this is an ASH review instead of an ASH preview).

If there was anything close to a "blockbuster" for Follicular Lymphoma at ASH this year, it was a session on Mosunetuzumab. All of the presentations I have been writing about take different forms, and there are kind of ways to tell how important the ASH community thinks they might be. One sign is how big the room is where the information is presented. If they expect a lot of people will be coming to hear about it, they'll put it in a big room.

The Mosunetuzumab presentation was in a big room.

 (And thanks to the anonymous reader who commented about this. You were a couple of days ahead of the cancer news sites.)

Mosunetuzumab has been on my radar for just about a year. It created some excitement at last year's ASH conference, and when I had my first appointment with my newest oncologist, he mentioned it as something we might consider if and when I need treatment again. The hospital I go to for appointments is participating in the clinical trial for Mosunetuzumab.

If you pay attention to treatment names, you now that Mosunetuzumab is a Monoclonal Antibody, or a MAB, which is why the name ends in -mab. Rituxan is a MAB, too -- I usually use that name, but its non-branded name is Rituximab, and in some parts of the world, it's known as MabThera.

What makes Mosunetuzumab different from a MAB like Rituxan is that it is "bispecific." Rituxan works by targeting a protein called CD20, which is on the surface of the cancer cell. When it comes across a cell with CD20, it attaches itself and works to kill it off. Mosunetuzumab also finds cells with CD20 and attaches itself. But it also finds immune cells with a protein called CD3 and attaches itself to them. "Bi" means "two." A "bispecific" MAB attaches itself to two cells -- one that it hopes to kill off, and one (an immune cell) that can help it do the killing.

So you can see why, in theory, it could be an effective treatment.

"Theory" is nice, but what about in reality?

 Well, there was a reason it was in a big room.

The session was called "Mosunetuzumab Induces Complete Remissions in Poor Prognosis Non-Hodgkin Lymphoma Patients, Including Those Who Are Resistant to or Relapsing After Chimeric Antigen Receptor T-Cell (CAR-T) Therapies, and Is Active in Treatment through Multiple Lines."

 The title kind of gives the highlights, but here are some of the details.

The study is a phase 1 trial, so in addition to measuring how effective Mosunetuzumab is, the study also looked at safety, and at dose escalation (figuring out how much to give to be most effective and most safe).  There were 218 patients in the study, and 69 of them had Follicular Lymphoma. Another 29 has transformed FL. 16 patients had already received CAR-T (4 with FL, 5 with transformed FL).

The results were very positive. For patients with indolent lymphoma (including FL), the Overall Response rate was 64.1%, and the Complete Response rate was 42.2%. For patients who had already had CAR-T, the ORR was 38.9% and CRR was 22.2%. (That's important, since about 2/3 of CAR-T patients relapse, and the need for a follow-up treatment is great for them.)

After 6 months, the patients who has received a CR were still mostly doing well -- 83% of patients with indolent lymphoma still had a CR, as did 71% of patients with aggressive lymphoma.

Also, 4 patients who had stopped responding to Mosunetuzumab had a response when they were treated a second time, with one of them having a CR.

Based on the number of news stories I have seen in the last few days, there is a lot of excitement in the lymphoma community about Mosunetuzumab's potential. Like all immunotherapy, it uses the body's immune system to fight cancer cells (which can usually escape the immune system). CAR-T is a very effective immunotherapy, but takes time and a lot of money to develop, since it is made specifically for each individual patient. Mosunetuzumab is an "off the shelf" treatment (a phrase that lots of experts have used -- it doesn't need to be specially made for each patient).

How effective will Mosunetuzumab be? We'll have to wait to find out. Long-term results will take time to figure out, and the dose escalation (how much to give to be most effective) is still being worked out. This is a phase 1 trial, after all.

It all reminds me a little bit of R-Squared. Lots of early excitement. Let's hope the same results comes about -- an alternative to chemo that is safe and effective and gives us another option.

Lympho Bob on Stage

Despite the title of this post, I'm not going to be performing on stage anytime soon (though my family can tell you that I think I would absolutely kill as Tevye in Fiddler on the Roof.  As long as the director went with my interpretation of "Do You Love Me?").

It also doesn't mean that my life story is going to be performed onstage anytime soon, either. Two years of watching and waiting doesn't make for riveting theater. Plus, Waiting for Godot pretty much covered that already.

But I found out yesterday that Lympho Bob made it into a play that was performed Off Broadway earlier this year.

The play is called God Said This, and it was written by Leah Nanako Winkler. It won the 2018 Yale Drama Series competition. Nanako Winkler's own website describes it like this: "James, a recovering alcoholic seeks redemption from his family when his wife is diagnosed with a rare and aggressive form of uterine cancer. John, a thirty-something single dad searches for a legacy for his only son while Hiro, a single NYC transplant struggles to let go of the demons she inherited. Sophie, a born again Christian, confronts her faith as she comes to terms with the inevitable death of her parents, her own shortcomings and some broken dreams. This is a play about five Godless and God-loving people in Lexington, Kentucky who face mortality in very different ways."

The introduction to the written version of the play talks about the identity issues that it brings up -- how the labels that are put on us can affect us as we accept, reject, and come to terms with them.

In one part of the play, characters read from what others have said online about having cancer. That's where Lympho Bob comes in:

If you can't see the image, it includes the character James reading the quote "Right now, I'm scribblin' in the sunshine on a notebook littered with bumper stickers from Gotcancer.org -- thanks for the rec Lympho Bob. My favorite? The one that says CCKMA: CANCER CAN KISS MY ASS!!!!!"

So it's not like I'm a character or anything, or even that a character talks about me. It's a character reading from someone who talks about a website recommendation that I made on the blog. Like, five levels from actually being me.

Still, how cool is that?

It gave me a lift. I've been in one of those periods lately where I'm a little overwhelmed with other things, and I can't give the blog and my other cancer advocacy the time and attention that I'd like to. So that little reminder that I'm reaching people was really nice.

Plus, the play sounds great. So many connections for me -- I go to a Yale hospital, I grew up in and now live in the northeast, but I lived in Kentucky for 5 years. And, of course, the whole idea of thinking about Identity is something I've been kind of obsessed with for a few years -- what it means to be a "cancer patient" or a "survivor" and how the words we use to describe ourselves, and the words others use to describe us, can affect the way we deal with the disease. It's something I write about a lot in small ways. I'm working on a big piece that looks into it more deeply, but it's a ways off. Still thinking it all through.

I wish I'd known about Lympho Bob the reference in the play earlier. I'd have brought the whole family to see it. We're a very easy train ride from New York City, and we see shows there all the time. Maybe I'll get lucky and it will be performed nearby again sometime soon.

(In the meantime, cancer really can kiss my ass.)

ASH Preview: The Leonard List

For this post, I'm letting someone else do the previewing: Dr. John Leonard, Lymphoma Rock Star and oncologist at the Weill Cornell Medicine in New York.

Every year, Dr. Leonard creates the "Leonard List," his Top 10 abstracts at the ASH conference. He counts them down on Twitter in the days leading up the ASH, and then discusses them in more detail (and adds 5 more as a bonus) on a podcast.

The podcast, which you can find here, is easy to access.

This year's Leonard List includes a lot of discussion about DLBCL (Diffuse Large B Cell Lymphoma). It seems like every year there is one type of blood cancer that has a bunch of exciting things happening, and from this list, it seems like DLBCL is the star this year.

Unfortunately, that means Follicular Lymphoma is not the star. That doesn't mean there isn't good stuff happening this year, just not the big, important things that are happening for other diseases.

But he does include 2 Follicular Lymphoma abstracts on his List.

The first is #9 on his list: "EARLY STAGE Follicular Lymphoma: First Results of the FIL 'Miro' Study, a Multicenter Phase II Trial Combining Local Radiotherapy and MRD-Driven Immunotherapy." For this study, researchers looked at FL patients with stage 1 or stage 2 cancer. As they note, many patients at this stage can receive traditional radiation treatments and can possibly be cured. Because the FL is localized (staying in one or two spots), a beam of radiation can take care of it.

For this study, patients were given radiation, and then were given immunotherapy (in this case, Ofatumumab, which is anti-CD20 monoclonal antibody, like Rituxan). After the radiation, the patients were tested for MRD -- Minimal Residual Disease. Basically, this means  finding very small amounts of cancer cells left over after the treatment was finished. Those with MRD were then given the immunotherapy, which helped clear the small amounts of disease that were left.

As Dr. Leonard points out, the techniques for finding MRD are still being developed, but he thinks this idea of measuring for them as a way to guide treatment is innovative and might be very useful in the future.


The second Follicular Lymphoma presentation that made the List is his #3: "Evaluation of the m7-FLIPI in Patients with Follicular Lymphoma Treated within the Gallium Trial: EZH2 mutation Status May be a Predictive Marker for Differential Efficacy of Chemotherapy."

Dr. Leonard likes the idea of m7-FLIPI. It made his List in 2016, too.

 m7-FLIPI is an updated version of the FLIPI index, which is meant to guide researchers who are developing clinical trials by making sure everyone in the trial is similar in terms of age, grade, etc. It's a misunderstood tool that too many patients use as a way of understanding how severe their disease is. Read more about FLIPI here, at Lymphomation.org. And don't use it to try to understand your own disease -- it will only cause you unnecessary stress.

The m7-FLIPI takes the traditional FLIPI and adds seven biomarkers. This is supposed to make the FLIPI index more accurate -- age doesn't tell us much about which patients might run into problems, but the presence of certain gene mutations in a cancer cell could probably tell us more about individual patients.


In this research, patients had biopsies that allowed researchers to look at gene mutations. Many were classified as high risk by the FLIPI, but were then reclassified as lower risk by the m7-FLIPI (which would seem more accurate). Patients in the study were given Immunochemotherapy (either CHOP, CVP, or Bendamustine, plus Rituxan or Obinutuzumab). The big takeaway here is that EZH2 gene mutation resulted in longer Progression Free Survival in patients who had CHOP, but not in Bendamustine.

As Dr. Leonard points out, there are lots of reasons why this needs to be tested in another study to confirm, but hes excited at the idea that a biomarker like the EZH2 gene mutation could be used in helping doctors decide which treatment would work better. That's the goal, after all -- using something in the cell to hep decide how to treat. It's a step forward in this process, not the final step.

The ASH conference begins in less than a week. I'll take a look at a few more FL abstracts that seem interesting to me. I'm not an oncologist or a cancer researcher -- just a Cancer Nerd who is a patient, as I like to remind you all. So I always enjoy hearing what actual experts like Dr. Leonard find interesting and exciting.

Thankful

Today is Thanksgiving in the United States (I know some of you aren't from the U.S.). It's the one day we set aside in the year to be thankful.

Of course we should be thankful every day, and we probably are, but it's good to set a day aside and truly think about the good things we have in our lives, even when our days can seem overwhelmed by bad things (which happens sometimes with cancer patients).

It's close to the end of the year, too, so it's a nice time to reflect.

For my family, this is definitely a transition year. For all of my married life (almost 27 years), my wife and I have taken ourselves and our kids to either my family's house or her family's, a trip of somewhere between 2 and 6 hours. Which has been nice. Thanksgiving is often about being with family.

My dad died last year, just over a year ago, a few weeks before Thanksgiving. My mom died about five years ago. Both from different forms of cancer. So this isn't my first Thanksgiving without them. But it's the first I've had a chance to really think about it.

My wife's mom died about two years ago. (Her dad died many years ago.) So it's not our first Thanksgiving without her, either. But there's a wedding coming up in a few weeks in my wife's family, a very happy occasion, but one that will kind of change the dynamic in some ways on her side of the family, too.

So this Thanksgiving feels a little different. Lots of change.

But that doesn't mean I don't have a lot to be thankful for. In fact, it feeling a little different this year just helps remind me of those goof things.

I'm thankful for my kids. My daughter went away to college in September, and my sons are both still in school (my oldest is almost finished). Our house has been quieter. For Thanksgiving, we'll have all of them home together for the first time in a few months. It's great to have them all here. I'm so thankful that they've grown into smart, caring people who want to help others and see some change in the world.

I'm thankful for my brother and his family. We'll be spending Thanksgiving with them. After my dad died, my brother and I spent a lot of time together, going through dad's things and settling everything that needed to be settled. It wasn't very fun, but we had each other. Just like we have each other now, and I'm thankful for that.

I'm thankful for my wife's family. I now there is a long history of "in-law" jokes, and we're kind of supposed to dislike our spouse's parents and family and dread spending time with them. Not true for me, and it shouldn't be true for anyone. If you love your spouse, his or her family shaped who they are, right? So there must be some good in them. For me, there's lots of good. They've always been supportive of us and our kids. I'm thankful for them, too.

I'm thankful for my health. I'm still here, almost 12 years after I was diagnosed with Follicular Lymphoma, so there must be something to be thankful for there, right? It's been almost 10 years since I had Rituxan, and even though I've never had a completely clean scan, for the most part, I'm a healthy person. I'm not a complete picture of health -- I'm 52, so I can hurt myself gesturing to someone while I'm giving them driving directions -- but I'm healthy, and my cancer is in check. I can work full-time and go to the gym and generally do the things I want to do. So I'm thankful for that.

And mostly, I'm thankful for my wife. She's been my rock. Go back to the beginning of this blog, and you'll see that. In difficult times, she's pulled me up. And in good times, she's shared the joy with me. Our lives are a little different this year, with some new challenges, good and bad. But we face them together, and we deal. Like we've been doing for these 12 cancer-y years.

So I wish you all a Happy Thanksgiving, and if you're not celebrating, I wish you all a peaceful day, full of things that you are thankful for.

ASH Preview: Long-Term Results of RIT

Back to ASH Previews.

The next one I found interesting is "Long-Term Outcome of Patients with Low-Grade Follicular Lymphoma Treated with Yttrium-90 Ibritumomab Tiuxetan: The Mayo Clinic Experience."

Yttrium-90 Ibritumomab Tiuxetan is better known as Zevalin, and it is a type of RadioImmunoTherapy, or RIT.

If you're new to Follicular Lymphoma, you may not eve know about RIT. It's a lot like Rituxan, in that it seeks out and attaches itself to cancerous B Cells (in fact, Zevalin attaches to CD20, the same protein that Rituxan attaches to). But RIT is different -- it has a little bit of radiation attached to it. Standard radiation that if often used on solid tumors just won't work on blood cancer. You can't hit a moving target, like a blood cell, with a beam of radiation. But RIT solves that by tracking down the cancer cells in the blood, attaching to them, and delivering that little bit of radiation right to the cell. Ideally, it cuts down on the typical side effects of radiation because it is targeted to specific cells.  

I'll admit, I'm fascinated by RIT. As a treatment, it hit its peak right about the time I was starting to understand my disease and learn more about it, and I know of a bunch of folks who have had more than 10 years of cancer-free living after RIT.

Unfortunately, it has never been used as much as it should have been used in the United States. Because it involves radiation, it requires extensive, specialized training in order to be administered. When it was first approved, there were also some related issues regarding how doctors were paid for it. Despite how effective it has been, the administrative difficulties have kept it from being used as much as it probably should be used.

Still, there is lots of research being done on RIT, including Zevalin (search this blog and you'll see few stories from 2018 on Zevalin), and a new RIT, Betalutin, was given Fast rack designation by the FDA last year. I'm hoping that if it does get approval in the U.S., they'll find a way to get it into patients.

As for this particular ASH presentation, the researchers looked at the long-term effectiveness of Zevalin in patients at one cancer center (The Mayo Clinic). Patients had low grade FL (grade 1 or 2). Basically, they wanted to see how Zevalin affected Overall Survival and how long patients went before needing another treatment.

Looking back at medical records, they found 137 FL patients had Zevalin between 2003 and 2018.

Median follow up was 10.2 years; median age of patients was 60, and 69% of patients were still alive.

For patients who had Zevalin as their first treatment, there was a 100% Overall Response Rate, and a 93% Complete Response Rate. For patients who had Zevalin as a second or later treatment, the OR was 93%, and the CR was 73%.

Of the 108 patients who a Complete Response, 45% of them still had that response a median of 7 years later. Only 43% of the first-line patients relapsed in that time, while 71% of the second-line patients did.

For the whole group, the median Progression Free Survival (how long it took for the disease to get worse or comeback) was 2.5 years, and the median Time To Next Teatment was 3.6 years. The PFS and TTNT numbers were better for the first-line group than the second line group.

Now the Big Number: media Overall Survival for the whole group was 18 years.  It was also 18 years for the second-line group, and a median hadn't been reached yet for the first-line group (since the median is the exact midpoint of the group, that means not enough people had died yet to measure the median -- a very excellent thing).

None of this very surprising to me, given the excellent long-term results in the people I now who had it years ago.

The researchers conclude that the numbers for Zevalin after almost 20 years are even better than they were when they first started measuring all of this. They recommend using Zevalin in combination with newer treatments as a way of extending their effectiveness.

That certainly seems like good advice. In fact, a recent study looked at patients who had Bendamustine + Rituxan, followed by Zevalin. The B + R had a 97% Overall Response, with a 56% Complete Response. When they followed it with Zevalin, there was again a 97% OR, but the CR went up to 89%.

It's good stuff, that RIT.

It would sure be nice if we could find a way to get it to more people who could be helped by it.

The Follicular Lymphoma Foundation

Good news for Follicular Lymphoma patients: yesterday was the launch of the Follicular Lymphoma Foundation.

The FLF was begun by Nicola Mendelsohn, who is a Facebook's Vice President for Europe, the Middle East, and Africa. She was diagnosed with FL in 2016, watched and waited for a year, and then did chemo. Things look stable now.

Her story is very familiar to a lot of us. She'd never heard of Follicular Lymphoma. She had no symptoms. She was married with 4 kids. She went back to work after she found out. She found a support group on Facebook (of course) and learned from others.

And, using her huge influence, she started a foundation to raise money for research. It's the first ever foundation for just Follicular Lymphoma -- no other lymphomas or other cancers involved.

If you're tapped into the online FL community (I certainly am), you know that the launch of the FLF was a big deal yesterday. Mendelsohn was interviewed on TV, and a number of magazines published stories about her.

Though the foundation is based in London, its major initiative will be to work with international organizations to find a cure for FL. Certainly, no matter where the research is taking place, it will help all of us.

This is a good thing. Head over the the FLF website and take a look around.

ASH Preview: R-Squared

Next up in previewing some of the research that I find interesting at ASH: some stuff about R-Squared.

R-Squared, if you're new to this, is the combination of Revlimid (also known as Lenalidomide) and Rituxan. A few months ago, the FDA approved R-Squared for some patients with previously-treated Follicular Lymphoma. And just yesterday, the Committee for Medicinal Products for Human Use recommended that the European Commission approve R-Squared for the same group of patients. That decision should come in about two months.

R-Squared is a big deal because it's the first combination approved for FL that does not involve some kind of traditional chemotherapy. Chemo can be very effective on FL, but with some side effects that can also damage a lot of healthy cells in the process. R-Squared is more targeted -- it spares healthy cells more than chemo does, but it also has a different bunch of side effects, sometimes also severe.

It's one of those treatments that oncologists get very excited about. It shows that there is promise for Follicular Lymphoma treatments that are not chemo.

There's still a lot of R-Squared research going on, particularly for patients with FL who have not yet received treatment. A fairly safe, effective, non-chemo treatment for first treatment would be another great option.

Two of the ASH presentations that I found interesting looked at just this issue.

The first is called "A Phase II Study of Lenalidomide Plus Rituximab in Patients with Newly Diagnosed Follicular Lymphoma: An Interim Analysis." This presentation is an "interim analysis" -- the phase II study isn't finished yet, but they're giving us some results. The researchers are from China, as are the patients. So far there have been 86 patients in the trial. Interestingly, the median age of the patients is 48, and the range of ages is 22 to 73. It's a fairly young group, compared to the typical age for someone diagnosed with FL, which is about 65. The results have been good so far, with 64 patients being evaluated. There is an Overall Response Rate of 90% (58 of 64), and a Complete Response rate of 81% (52 of 64). The side effects are manageable, and seem in line with the side effects in the previously-treated FL group.

A second interesting presentation on FL and R-Squared is "Predictive Factors of Response and Survival of Lenalidomide and Rituximab As Initial Treatment of Follicular Lymphoma." This study looked back at 98 FL patients who had been given R-Squared as a first treatment. Response rates were similarly great -- 98% Overall Response Rate, and a 90% Complete Response Rate, after 6 months. After 88 months (a little more than 7 years), 31 patients progressed or died. Only 3 patients had transformed disease, and 2 patients died (one from disease progressing, and one fro unrelated health issues).

The news looks good for R-Squared as a possible first treatment. There is a growing body of evidence (including these two reports) that shows good effectiveness with manageable side effects.

The weeks following a big conference like ASH often have announcements of FDA applications. The research gets presented at the conference, and pretty soon, the process starts for getting the treatment its official approval.

I don't now if that's the plan right now (the first one I looked at above is a study from China, and the second looks back at patients, rather than showing trial results), but my guess is the approval will be sought by someone soon.


 

ASH Preview: Doctor-Patient Communication for FL

The ASH Abstracts are here!

ASH is the American Society of Hematology, the country's largest organization for specialists in blood cancer and other blood diseases. Every year in early December, they hold their annual conference. And a few weeks before, they release the abstracts for the conference -- the summaries of the presentations that researchers will make.

Summaries can't tell you everything, but they do give the highlights. So every year at this time, I look through the abstracts for Follicular Lymphoma and right about the ones that look interesting to me. So maybe they aren't the most "important" (though if there is some major news, I'll write about that).

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

So here's the first one: "A Cross-Sectional Study of Unmet Needs of Lymphoma Patients in Patient-Doctor Communication: Follicular Lymphoma (FL) and Diffuse Large B-Cell Lymphoma (DLBCL)."

This presentation looks at data from the Lymphoma Coalition's 2018 Global Patient Survey, and it compares responses from Follicular Lymphoma patients and DLBCL patients about their needs for communication with their doctors. It seems to me that the communication, overall, is not good.

Overall, the survey looked at responses from 6631 lymphoma patients in over 70 countries. 937 of them have Follicular Lymphoma, and those were the responses that interested me most, of course.

As for ages 17% of FL patients taking the survey were under 40 (I was diagnosed at 40), and 33% were over 60. My math skills tell me that 50% were in their 40's and 50's. (That's not when they were diagnosed, just how old they were when they took the survey.)

As for communication,  65% of patients would have liked more information and support when they were diagnosed, but only 39% said their doctor encouraged them to have more discussion and 23% said they were referred to other places for support. 

About 70% of FL patients reported physical issues to their doctors, but only 42% reported emotional issues. Only 40% felt helped by their doctors for physical issues, and only 31% felt helped with their emotional issues.


62% of patients felt helped by doctors for treatment side effects, but only 33% felt helped for Fear of Relapse.

Before moving on, I think it's important to point out that this survey might not represent all FL patients. Since it was put out by the global Lymphoma Coalition, it seems to me that a particular type of FL patient was more likely to take it -- one that's more of an advocate, and maybe (as a result) one that is more critical. (I'm thinking of myself.) That might have made the numbers lower.

That said, the problems pointed out by the survey are troubling, especially with the way patients and doctors talk about emotional needs.

Troubling, but not surprising.

I've been saying for years that Follicular Lymphoma is an emotional disease as well as a physical disease -- maybe more so than for other cancers, because we often have no physical symptoms, and are waiting around for things to happen.

I wonder if that's part of the issue with FL patients not feeling like their emotional needs are taken care of. An experienced doctor might see the FL diagnosis and think "Slow-growing, we can watch and wait, I'm not too concerned yet." But a patient thinks "CANCER!" A doctor might see no physical symptoms and that means nothing to worry about. But a patient, as many of us know, can't help but worry.

I don't know if a survey like this will mean that doctors start to pay more attention to these things (my guess is that it won't). So that means it's on us as patients to ask for more. We need to insist that we get what we need, even if it isn't offered to us.

That's not easy when we're marinating in the emotions that come with a cancer diagnosis. But it's exactly the reason we need to.

Options for Newly-Diagnosed Follicular Lymphoma

Targeted Oncology has a nice piece on a presentation by Dr. John Leonard at the CFS (Chemotherapy Foundation Symposium) in New York this week. He spoke about the options for newly diagnosed Follicular Lymphoma patients, and the recent research that helps us understand them.

Basically, newly-diagnosed FL patients fall into one of three groups:
Localized Disease
Advanced Stage Disease with Low Tumor Burden
Advanced Disease with Symptoms

Each group has different choices for treatment.

Limited Stage or Localized disease is usually stage 1 or 2. About 70% of patients will not need treatment for 10 or 15 years, so watch-and-wait or radiation is appropriate, rather than chemo. Recent research shows that adding chemo or chemo + maintenance to patients in this group increased the time between treatments, compared to patients getting radiation, but all three approaches had the same Overall Survival.

For patients with advanced stage (3 or 4) FL, but with no symptoms, there are other options. (This is the group I was in when I was diagnosed.) Options for this group also include watching-and-waiting, but, according to Dr. Leonard, Rituxan is also an option, and can last in longer times between treatments.  Dr. Leonard cites research that shows that just 4 doses of Rituxan gave a median Progression Free Survival of just under 2 years, with 15% of the group progression free at 7 years. (I watched and waited for 2 full years, and then had straight Rituxan -- I haven't needed treatment in almost 10 years.)

The there's the third group -- they are diagnosed with advanced disease, with symptoms like large tumors or aggressive disease. The standard first treatment is either Bendamustine + Rituxan or R-CHOP. The B-R tends to have fewer side effects with the same effectiveness. Other options include Obinutuzumab instead of Rituxan, or R-Squared (Rituxan + Revlimid). Again, Dr. Leonard cites recent research that shows how well these treatments work for this group.

Dr. Leonard also pointed out that there are a whole lot of questions that still need to be answered (like whether or not we'll ever have something that's more effective than watching and waiting but with few side effects so it doesn't affect Quality of Life.

There are more choices than just these, of course -- and plenty of clinical trials for patients in all three groups. As always when I read about treatments, I feel good knowing we have some decent options right now, and there are more coming in the future.

How One FL Patient Was Treated

Targeted Oncology has another video series on Follicular Lymphoma. It features Dr. Jonathan Friedberg from the Wilmont Cancer Institute in Rochester, NY.

As with many of these video series, I find this one interesting because it provides some very up-to-date information about FL and one expert's opinions on that information. (That doesn't mean it's new information, which is OK, too. It's nice to now the stuff I already know is up to date.)

The series features Dr. Friedberg talking about newer treatments in Follicular Lymphoma, but what I find most interesting is the video called "59 Year Old With Relapsed Follicuar Lymphoma." In the video, Dr. Friedberg gives a case study of an FL patient.

Now, I've watched enough Call the Midwife by now that I could almost certainly deliver a baby by myself. And I've read enough about FL that could guess an expert's recommended treatment.

So I watched the video and made my guess.

Here's what we know (copied from the Targeted Oncology website):

++++++++++++++++++++++++++

Case: A 59-Year-Old Man With Symptomatic Follicular Lymphoma
A 59-year-old man presented to his physician with a 10-lb weight loss and chronic night sweats for the past couple of months. He complained of intermittent fatigue but is able to maintain his current exercise regimen.

H & P

• PE: enlarged bilateral axillary lymph nodes; enlarged spleen, palpable
• CBC: WBC, 12 X 10⁴ /L; platelets,103 X 10⁹ /L; Hgb, 9.2 g/dL
• LDH: 400 U/L

Biopsy

• Excisional biopsy showed grade 2 follicular lymphoma; CD20+, CD10+
• Bone marrow biopsy; 60% involved

Imaging

• PET/CT showed widespread lymphadenopathy and a large splenic mass measuring 10 cm
• Diagnosis: Stage IV follicular lymphoma

++++++++++++++++++++++++++

Any other amateur oncologists want to give this a shot?

No information on his previous treatment, so I went with Bendamustine + Rituxan.

I was wrong, as you will see if you watch the video. I won't tell you what the actual treatment was.

The lesson here? I'm not a doctor. I make that clear on the blog, and I always remind anyone who emails or tweets me for advice. The best thing you can do when you have concerns is to talk to yur doctor.

I could still deliver a baby, though.

Experienced Docs Are Best?

Just watched a really interesting video from the Yale Cancer Center.

It's a lecture from their Grand Rounds series, featuring Dr. Scott Huntington, an oncologist and lymphoma specialist.

"Grand Rounds" is a kind of lecture for medical students and working doctors. When a doctor "does rounds," it means visiting individual patients. When this happens at a hospital that is connected to a medical school, it often means having some medical students tag along to observe. (I'm sure this has happened to many of you, with good and bad results.) "Grand Rounds" are a way to present information without having a few dozen people crowd into a patient's room. One doctor presents a lecture, and everyone who attends gets the chance to learn. It's a good thing.

This Grand Round is called "Provider Volume and Cancer Outcomes: Moving beyond surgical settings and into the increasingly complex field of medical oncology." The video is about 25 minutes long, and I found it pretty interesting.

"Provider Volume" is a way of saying "doctor experience" -- a provider with greater volume is one who has more experience with a particular treatment. And as the research presented here shows, more experience can mean better patient outcomes.

The example that stood out for me had to do with Rituxan. (Naturally, I find that fascinating, since Rituxan and I are good friends.)

As you may know (maybe from experience), many patients have an allergic reaction to Rituxan during the first or second dose. It is usually taken care of with Benadryl and/or steroids, and the rest of the doses work out with no problems.

The research looked at a database of lymphoma patients who had given Rituxan (18,570 of them), and measured how many of them stopped treatment after 1 or 2 doses. The assumption was that patients who stopped early probably had doctors who were less experienced (that is, had a lower provider volume). A doctor with less experience giving Rituxan might not understand that, as long as the patients can be treated with something fairly easy, then rounds 3 through 6 or 8 will go much easier.

And that's exactly what they found -- about 7.6% of patients stopped early, compared to 1-3% in clinical trials. Doctors who had not given Rituxan to any patients were 57% more likely to stop after 1 or 2 rounds than doctors who had given Rituxan to 3 or more patients in the last year. Experience -- provider volume -- matters.

The next step in the research is to make the experience better for patients. The researchers are testing out a system where doctors who are inexperienced with a treatment will be given data that shows how other doctors have handled the situation. So instead of stopping the Rituxan early, they'll know that Benadryl or a steroid has worked in some percentage of cases. They'll be able to use other doctors' experience when they don't have their own.

It's a nice example of "Big Data" -- the term used to describe statistics that involve huge numbers of people -- being used to hep single, individual patients.

That's the goal.

Still No "Best" Trestment for Early Stage FL

According to research presented in the journal Blood Advances, there is still no "best" treatment for early stage Follicular Lymphoma.

I don't write a lot about early stage (stage 1 or 2) FL, for a couple of reasons. First, not many FL patients have it. Most of us are diagnosed with stage 3 or 4 disease. Less than 20% of us are diagnosed with early stage disease. Symptoms just don't show up very clearly at those stages.

The other reason is that there really isn't a lot of research on early stage disease. For many years, the thinking has been that early stage FL can actually be cured, in many cases, with traditional radiation. It makes sense -- staging is based on location. Stage 1 lymphoma is isolated to one area of the body. Radiation doesn't work on other stages because a single radiation beam can't get to it. But it can with stage 1.

But is that the best approach? That's what the Blood Advances article tried to answer.

The article is called "Outcomes of stage I/II follicular lymphoma in the PET era: an international study from the Australian Lymphoma Alliance."

The research looked at how effective a bunch of different treatments were on stage 1 and 2 Follicular Lymphoma -- Watching and waiting, radiation alone, systemic therapy (like chemotherapy), or  chemo + maintenance.

The big outcome is that they found that there was no difference in Overall Survival among all of the choices.

This is not a surprise. It's the golden ring that no one seems to be able to grab -- lots of treatments seem to do good things for FL patients, like increase time between treatments, or do the job with fewer side effects. But all of them seem to give the same survival benefit. They can do different things for us, but in the end, none of them keep us alive any longer than the next best one.

The patients that received Maintenance had better Progression-Free Survival. Again, not a surprise. That seems to be the case with many studies -- Maintenance keeps the disease from coming back longer than not getting Maintenance (though it does come with the side effects that come with long-term treatment). Better PFS, but with the same Overall Survival.  

The good news is that all of the different treatments resulted in "excellent outcomes."

And that's about where we are, still, with Follicular Lymphoma, with a few exceptions. We have lots of options, which lets us choose treatment based on our goals. The important thing is to know what those options are, know what your goals are, and have a doctor who is willing to talk about it all with you.