Intermediate Risk FL: One Patient's Treatment

Targeted Oncology has another short video series featuring an oncologist discussing one patient's treatment history. Like the one they did a couple of weeks ago about a patient with high risk Follicular Lymphoma, this one highlights a single patient's story. It's not supposed to be a description for how everyone in her condition should be treated, but it is interesting to see how an oncologist makes decisions.

This one features a patient with intermediate-risk FL, and the oncologist doing the describing is Dr. Peter Martin from Weill Cornell in New York City. The link will take you to the first video in the series; the others are linked to the right of the video box.

The patient is a 57 year old woman. A scan showed activity in lymph nodes near her collar bone and groin (stage 3), and a biopsy showed grade 2 FL. She also had low hemoglobin (which carries oxygen in red blood cells), making her intermediate risk.

Dr. Martin points out that the PET scan at diagnosis is valuable as a base line in case there is a suspicion of transformation later on. [That's one of those things that I like about the Targeted Oncology series -- the oncologists who do them are very good about explaining their reasoning, something our own doctors don't always do.]

The patient was treated with Bendamustine and Rituxan initially. Again Dr. Martin discusses soem of the reasoning; he considers GELF criteria, which inolves looking at "organomegalies [enlarged organs], cytopenias [low blood counts], elevated LDH [Lactic Acid Dehydrogenase, which shows possible tissue damage], and the size and number of lymph nodes [pretty sure we all know what that means]." In this patient's case, the cytopenias and fatigue were enough to say she needed to be treated early (low red blood cell count).

Dr. Martin also discusses the uses and limitations of FLIPI scores.

They might be useful in giving a  general idea of "where a patient is headed," but it doesn't say anything about an individual patient's survival or how they might react to treatment.

Again, Dr. Martin provides some reasoning behind the decision to go with B + R. Another option might be straight Rituxan. Interestingly, he says the patient's age and the fact that is probablly still working would be a factor in using Rituxan only -- minimal disruption to her Quality of Life. He also discusses other possibilities, like R-CHOP, as well as the possibility of using either Rituxan or Obinutuzumab maintenance.

Four years later, Dr. Martin saw the patient again. She was experiencing fatigue again, and a scan showed that the nodes near he groin were large again. There were no other signs of transformation, so he didn't do a biopsy. They tried R-Squared (Rituxan and Revlimid/Lenalidomide), which worked well.

Again, Dr. Martin discussed the reasoning for the decision. The patient wanted something that would put her in remission for a while, but without too intensive a treatment (again, seems like a Quality of Life issue). One thing to consider for R-squared is how long to keep it up. Dr. Martin's preference is to not use it any longer than necessary.

Two years later, the patient again needed treatment. There was more activity throughout her body, though the scan didn't show evidence of transformation. She was given Idelalisib, a PI3-kinase inhibitor. Once again, Dr. Martin discusses his reasoning for the choice -- one consideration was that the inhibitor works in ways that are different from the first two treatments, which makes sense, given that the other two types stopped working. The decision also had, again, Quality of Life considerations -- as Dr. Martin says, "Idelalisib is an oral therapy, so it’s easy to do. It requires some blood monitoring and some clinical monitoring after that. But it doesn’t require a lot of intravenous infusions, doesn’t cause hair loss, is relatively easy to administer, and is easy to take, and as long as we’re cognizant of the potential side effects and looking for them and being ready to act on them, it’s something that can be done relatively easily."


So, once again, an interesting description of one person's treatment, with a nice description of the reasoning behind all of the decisions. It won't be the same for everyone, since everyone's disease will act a little differently. But it does give us a lot to think about.


I'm hoping they do a series now on low-risk FL, and it's basically 25 minutes of the oncologist talking about how boring the office visits are since the patient is watching and waiting and they just talk about baseball instead (which is what mine were like).


No, really, there are plenty of decisions to be made even for low-grade FL -- whether to treat or watch and wait, which treatment to try, and certainly what kinds of Quality of Life factors are important to the patient.


I'm looking forward to that one.

Predicting Progression Free Survival in Follicular Lymphoma

I'm about a month late to this, but it's very interesting news for Follicular Lymphoma patients.

Researchers believe they have found a gene expression model that can predict which FL patients are high risk and which are low risk.

Some background and reminders: one of the big pieces of news about FL in the last few years is the discovery of PFS24 -- patients who receive Immunochemotherapy (usually a monoclonal antibody plus chemo, like R-CHOP or R-Benda) but then do not get to 24 months of Progression Free Survival (the disease comes back or gets worse within 2 years) have a lower rate of Overall Survival.

It's good that researchers have identified that. The problem is, they don't know if someone is on that PFS24 group until they get the Immunochemo and then get worse.

The research suggests that looking at a genetic profile of the patient's cancer cells mighty help them make that prediction right away, at diagnosis.

The researchers looked at biopsies from patients who were in the PRIMA trial, which is examining the effectiveness of maintenance. They identified 395 different genes that were related to disease progression. Some of the genes are directly involved with Follicular Lymphoma, and some affect the microenvironment of the cell (that is, they allow things to happen or not happen that keep the cancer cell alive longer than it should be).  Using some statistical analysis, they were able to figure out which 23 genes affect the cell in a way that make a patient "high risk."

They could then go to the patients who were biopsied, and see what their results were. They found that those who were considered high risk in their model had a 5 year PFS of just 26% (only a quarter of the patients had not had their disease progress in 5 years). The low risk group had a 5 year PFS of 73%.

They then used this model of 3 other groups who were participating in different trials, and the model held up -- the media PFS for the high risk group was 3.1 years, and the low risk group was 10.8 years.

So there seems to be some validity with the model. At the time a patient is diagnosed, they can be categorized as high risk or low risk. No need to wait to see how they respond to treatment.

The big question is, of course, How does this actually play out in the doctor's office? If I find out I'm high risk, what can I do about it?

Well, the researchers here seem to suggest that there's not much you can do -- at least not yet.

According to the researchers, "Despite recent progress in the stratification and management of patients with follicular lymphoma, a substantial proportion of patients are still underserved by existing standard treatment and have rapid progression of their disease...Our gene-expression predictor could be valuable in the clinical setting to identify patients at high risk or low risk of progression so as to adjust the therapeutic strategy and enrollment for innovative treatments....For patients with high-risk FLIPI and 23-gene scores, having a 50% risk estimate of lymphoma progression at 2 years, new treatment options should be developed."

Note the wording: this is a first step. For now, doctors might be able to "adjust the therapeutic strategy" and suggest a more aggressive treatment right from the start, or encourage "enrollment for innovative treatments" such a clinical trials. But in the end, "new treatment options should be developed," suggesting they aren't here yet.

Or maybe they are. There are already treatments based on gene expressions. Possibly combining them might target several of the gene expressions in that group of 23. Or perhaps newer treatments will be developed instead.

Whatever the case, it seems to be another piece of the fabulous puzzle that we call Follicular Lymphoma. It brings us a little bit closer to understanding how it all works and what we can do to bring it under control.

And while it probably won't help those of us who have already been diagnosed, this knowledge might help some of those folks who aren't yet diagnosed, and make their lives just a little bit better.

Dogs and Cancer

I found out this morning that today is National Puppy Day!

It's kind of one of those made-up "holidays" that I keep reading about on Facebook, but I don't care. I love dogs.

A couple of things to read if you're a dog lover, too, and interested in cancer (which I know you are -- why else would you be reading this blog?).

The first one is from a couple of days ago -- a dog was able to detect her owner's skin cancer.

There's a long history of dogs who have been able to detect cancer. They are certainly not as accurate as a CAT scan (ha!), but they could be a good first step.

The first cancer-sniffing dog was a Standard Schnauzer named George. My own dog is also a Standard Schnauzer. Her named is Strudel, because she's very sweet and a little nutty. Unfortunately, she is not at all good at sniffing out cancer. She's 11 now, and getting crankier as she gets older.

I'd love to think we can teach her some new tricks, but cancer detection is probably not going to be one of them, even though she is very smart:

(You can tell she's smart because she wears glasses.)

The other article I want to share was published yesterday -- "How Dogs Are Helping Us Understand Cancer." Turns out we can learn a lot about human cancer by studying dog cancer. That link will take you to an article that includes a video documentary on the topic. Fascinating stuff.

(I have a doggy friend going through chemo now, which makes me sad. But dogs rarely seem to get sad, which I take as an inspiration.)

So hug any puppies (whether they are 11 weeks or 11years) that you know today.

And if anyone wanted to share pics of their dogs, I would be totally OK with that.

High Risk Follicular Lymphoma: One Patient's Treatment

Targeted Oncology just did a really nice series highlighting how one oncologist treated one patient with high risk Follicular Lymphoma.

Now, of course, every one of us is different, and one patient's story doesn't tell us anything about our own disease and treatment. each of us will have to work that out with our own doctor. But I thought it was pretty interesting to see how this oncologist made decisions for this patient.

If you want to watch and read for yourself, the article/series is called "Approach to High Risk Follicular Lymphoma," and the link is here. There is a video near the top of the page, and clicking the boxes to the right of the video will let you see the next videos in the series. The transcript of the video appears below.

The doctor is Ajay Gopal from the Seattle Cancer Care Alliance, and the patient he is discussing is a 62 year old man with left axillary adenopathy (swollen nodes in his left underarm). Bloodwork was normal, and a biopsy of the nodes showed stage 2 FL. A PET scan showed FL in other areas, plus 30% bone marrow involvement.

Here's where the cancer nerd in me think it gets interesting -- if I were this patient, what kind of treatment would I want?

As Dr. Gopal points out, there are some choices here. Watch and Wait? Since he has symptoms, this was ruled out. Rituxan or other innumotherapy? Maybe, but that's more likely for a patient with low tumor burden. They went with Rituxan + Bendamustine. Interestingly, Dr. Gopal pointed out that R-squared (Rituxan + Revlimid) could also be appropriate for this patient, but it is not yet approved by the FDA for FL, so cost would be a factor -- insurance won't pay for it. It's nice to hear that patient cost is something that doctors think about.

B + R seemed to work well, but 18 months later, the patient came back with new symptoms -- weight loss and fatigue. Another scan showed that the FL had gotten worse. Dr. Gopal also points out that a short remission of 18 months should mean a new biopsy as well, to make sure the FL has not transformed. An 18 month remission puts this patient in the high risk category -- that PFS24 group that does not achieve 24 months of Progression Free Survival (about 20% of FL patients).

They decided to go with R-CHOP, but the patient did not tolerate it well. After only 2 cycles, he developed anemia (low red blood cell count) and the fatigue that goes with it. He had a Partial Response after the 2 rounds of CHOP.

Unfortunately, after only 5 months, he developed new symptoms again -- a feeling of fullness in his abdomen. An exam showed a swollen spleen and low platelet counts. This time, a new biopsy showed the FL had progressed to grade 3, with bone marrow involvement at 90%. As Dr. Gopal points out, the biopsy did not specify if it was grade 3A or 3B, which is an important distinction, since grade 3B is basically considered Diffuse Large B Cell Lymphoma, and would require much more aggressive treatment.

The question now is, which treatment to try next? Since he had trouble with reactions to chemo, a more aggressive chemo (such as RICE) was ruled out. An Autologous Stem Cell Transplant was also a possibility. Because the patient had several bone marrow-related problems, they needed to consider whether there was some kind of marrow disorder, too.

In the end, the choice was Idelalisib, a PI3-kinase inhibitor. More targeted and less harsh than traditional chemotherapy, it could do the job. Other choices were Copanlisib, another PI3-kinase inhibitor, and Zevalin, the RadioImmunTherapy.

The patient went on Idelalisib, had some side effects that were dealt with, and remains on it after about 5 months.

Dr. Gopal ends with the reminder that there are other treatments on the horizen that might be available in the future, including Revlimid and CAR-T.


Again, as I said, one patient's story really doesn't tell us much about out own. Mine has certainly been very different from this patient's -- my age, my health concerns, my stage and grade, my reactiosn to treatment. His path wouldn't work for me.

But I think it's really interesting to see what kinds of factors his oncologist considered with each step -- which health issues mattered, which treatment options were on the table, and which choices were made. It's good for each of us to consider what kind of map we might need to follow when the time comes.

And it emphasizes how important it is to have a doctor who is open to conversations about those choices. As patients, we certainly should have a voice.

RIT for FL: Betalutin

I've been talking about Betalutin for a few months now -- since the ASH conference, I think -- so I suppose it's time I wrote about it, huh?

It's especially timely since we've seen good news with RadioIummnoTherapy (RIT) in the last couple of months, too, with research showing that it is effective and safe.

Just as a reminder -- RIT is a type of radiation therapy. Conventional radiation therapy is effective on some types of solid tumors. Not so much on most blood cancers, where the cancer cells are floating around to much to shoot at them with a beam of radiation. RIT solves that problem -- it attaches a tiny bit of radiation to an antibody (something like Rituxan) that seeks out and attaches itself to a protein on the cancer cell (Rituxan attaches to CD20). The result is, ideally, the benefits of radiation without the side effects, since the radiation doesn't travel too far beyond the cancer cell.

Betalutin is, of course, another type of RIT.

There have already been a couple of other RIT treatments approved in the U.S. -- Zevalin, which is still around, and Bexxar, which is no longer being made. (Why? More on that below.)

Betalutin in a little different from other RIT treatments. It stays in the body a little bit longer, so it can kill off more cells, and the radiation it releases doesn't travel as far, so it should spare more healthy cells nearby. Most importantly, Betalutin targets CD37, rather than CD20. So for patients who are refractory to Rituxan (that is, it has stopped working for them), Betalutin could be a more effective option.

Someone sent me a link for a really nice video explaining how Betalutin works. Watch it here.

Researchers presented data for Betalutin at ASH in December. In the phase I/II trial, 61 patients were given straight Lilotomab (the monoclonal antibody that targets CD37), and then Betalutin (Lilotomab plus the bits of radiation). The study has 4 different arms, with patients receiving different doses to test which one works best (this is common in early trials). One arm seems particularly effective for Follicualr Lymphoma patients, with 81% of the 21 FL patients showing a Response, 28% of them showing a Complete Response. (You can look at the ASH abstract link for more details of the study, including safety issues, which were pretty good.)

Updated data were presented at the ASH meeting (you can see some of the numbers here).

As always, there are a couple of things worth mentioning.

First, this is an early trial. Approval in the U.S. would not happen for a while, assuming a phase III trial goes as well. Given that the makers of Betalutin are targeting patients who are refractory to Rituxan, it seems like they have a good target population that needs treatments. But it will be a while before this is available.

Second, and maybe more important, is that RIT faces some barriers in the U.S. The rules for handling radioactive treatments are strict -- it cuts down on the number of doctors who can administer it. It's a big reason why Bexxar could never get a grip, and why Zevalin is so under-used, despite its effectiveness. The video I linked above does mention that Betalutin comes in a ready-to-use formulation. I don't know if that makes it easier to administer, or if those same limitations will apply.

(You might remember Lymphomation made an effort to advocate for lymphoma patients by getting Congress to change those rules. It's never too late to get in touch with members of Congress to educate them about our disease and its treatments.)

So, bottom line is, in my opinion, Betalutin could end up being an effective treatment option for FL patients who are refractory to Rituxan. And you know I'm always in favor of having more options for us. This could be especially true for patients in Europe and other parts of the world where there is more enthusiasm for RIT.

As for the U.S., it's going to be a tougher road, but not a completely closed one. Just bumpier.

ASCO's Cancer Advance of the Year: CAR-T

It seems like I've been writing a lot lately about CAR-T. But I guess that's because it's been in the news so much lately -- lots of lymphoma experts are very excited about it. And with good reason. The results from trials so far have been pretty amazing.

(In my last post, I mentioned the CAR-T and Follicular Non-Hodgkin's Lymphoma Blog. One of its contributers, William, added a comment to that post about his and his wife's experience -- you might want to check it out.)

Last week, ASCO, the American Society of Clinical Oncology, released its top cancer advances for the last year, and CAR-T came in at #1. That's a great endorsement for the treatment (not that it needed another one for everyone to realize how great its potential is).

For now, CAR-T's approved use in lymphoma is only for aggressive B cell lymphomas, including transformed Follicular Lymphoma. There are trials that look at its use in indolent B cell lymphomas, like the slow-growing versions of FL that many of us have.

CAR-T involves removing a patient's T cells and changing them, so the treatment is about as personalized as you can get. However, there are attempts at designing a CAR-T treatment that is "off the shelf" -- one that anyone can use, with the potentially complicated and expensive personalization process. If an effective version of that can be developed, then we'll really have something.

The ASCO report listed a bunch of other cancer advances form the last year, too. Not all of them deal with blood cancers, but a few of them should mean something to those of us with FL:

• Researchers and oncologists are (maybe slowly) paying more attention to Quality of Life issues. As treatments become more targeted, side effects should be less severe, and so Qulaity of Life should be better.
• Last year, the FDA approved the first "tissue-agnostic" cancer treatment, Pembrolizumab, also known as Keytruda. "Tissue-agnostic" means that it was not approved for a cancer of a specific body part (blood or stomach or breast). Instead, it targets a biomarker that shows up on cancers from a bunch of different places in the body -- skin, blood, brain, lung, head and neck. It's not yet approved for FL (though results from a phase 2 trial with Rituxan look pretty good). More importantly, it's a huge shift away from the way researchers have always thought about cancer. We don't just focus on a body part, but instead on the genetics underneath it all.
• The report also talks about cancer prevention -- stop smoking, and don't drink so much alcohol. Too late for us to prevent getting FL, but there is evidence that we can increase our survival with other lifestyle changes, including getting more exercise. 

I always enjoy reading about how excited cancer experts can get about the research they are doing. That's the vibe I get from the ASCO report -- lots of good things happened in the last year, and there's lots more to come.

Lots of reasons for hope.

When FL Patients Have Power

I'm going to link to another article by Jamie Reno, journalist and Follicular Lymphoma patient.

This piece is called "You Say You Want A Revolution? Cancer Patients Gently Wrest Control of Groundbreaking Immunotherapy Conference."

The first part of the article talks about the ImmunoTX Summit, a two day conference in California with presentations on immunotherapy treatments for various types of cancer. Immunotherapy, of course, involves using the body's immune system to fight off cancer. There are lots of immunotherapy treatments already in use, and lots and lots more (Reno says "thousands") in clinical trials.

As he describes the conference, the immunotherapy getting the biggest buzz these days is CAR-T, or Chimeric Antigen Receptor T cell therapy. I've posted about CAR-T a bunch of times. CAR-T involves removing T cells from the patient (T cells are an important part of the immune system -- they attack invaders, but not cancer cells, which technically aren't invaders from outside the body like a virus is). The T cells are changed so recognize the cancer cells and attack them.

The results from clinical trials for CAR-T have been pretty fantastic, with a lot of success stories. (I'll remind you to take a look at the CAR-T and Follicular Non-Hodgkin's Lymphoma blog. It's put together by Ben, who had a successful CAR-T treatment, and William, whose wife had a successful CAR-T treatment). Lots of great up-to-date links to explore.

It sounds like the ImmunoTX conference was great, with lots of big names in the field as speakers.

But if you look at the title of Reno's article, there's more to it than just talk about CAR-T and other treatments. It's about patients being empowered.

And that happens in a few different ways.

I love the way he describes patients as feeling more involved in the process when they have CAR-T as a treatment. "The patient's own body is the drug," he says.

That is so cool.

I've told stories about feeling like my doctor isn't listening to me, and how frustrating that is. (You can read one of them here -- a post I wrote for the Savvy Co-Op blog.) Not only does the treatment make patients feel like they are in more control of things, but their doctors seem to actively encourage the feeling. We need more of that.

And another example: CAR-T is expensive, costing roughly $400,000 for the treatment. (I'll let you international folks do your own monetary conversions for that one.) Reno tells the story of one patient who wrote a proposal to her insurance company, showing that one CAR-T treatment, if successful, would cost less than the repeated treatments she would likely face otherwise.

That's what patient empowerment is all about.

And then there are the patients who are pushing for clinical trial reform, changing the ways they are conducted so more patients have access to them. (And it's not just patients who are advocating for this -- lots of doctors, too, especially the ones who work outside of research hospitals where trials usually take place. That's a really complicated situation, with lots of hard work to balance access, safety, and effective science, as I found out recently.)

The important thing is, patients are using their voices, and doctors and others in health care are starting to listen.

Finally, the article talks about an advocacy group called COLONTOWN, made up of colon cancer patients and advocates. They work together online and go to conferences to make sure that patients' voices are heard.

I like Reno's article because it shows so many different ways that patients can recognize and use their power to make a difference. Sometimes that's in really big ways, like trying to get clinical trials reformed. And sometimes it's banding together with others to make sure the patient's perspective is included in conversations about treatments and other issues.

But I also know that taking on big issues can be hard. A lot of us don't have the time, or the energy, to make Big Changes. It is, frankly, intimidating.

And that's OK.

Take on the small changes, but the ones that might hit closest to home. Make your voice heard by your own doctor. Ask questions and make sure you get answers. Be informed. Listen and respond. All of us can do that.

The important thing is, find the place where you have power. And then use it.

Life Lessons

March 4 is the 25^th anniversary of one of the most famous Cancer speeches in history.

Jim Valvano, perhaps better known as Jimmy V, received the first Arthur Ashe Courage and Humanitarian Award at the first ESPY awards ceremony on March 4, 1993. Jimmy V was most famous at that time for being the coach of the North Carolina State University men’s basketball team, underdogs who won the national championship in 1983.

When Jimmy V won the Arthur Ashe award and gave his speech, he was just a couple of months away from the end of his life. He had metastasized adenocarcinoma, a glandular cancer.

In his speech at the ESPYs, he offered some advice:

“To me, there are three things we all should do every day. We should do this every day of our lives. Number one is laugh. You should laugh every day. Number two is think. You should spend some time in thought. Number three is you should have your emotions moved to tears, could be happiness or joy. But think about it. If you laugh, you think and you cry, that’s a full day. That’s a heck of a day. You do that seven days a week, you’re going to have something special.”

I saw Jimmy V make that speech 25 years ago on TV. At the time, I thought it was inspiring, but as a young healthy man, it didn’t mean much to me.

Five years ago, on its 20^th anniversary, I heard it again, on the radio as I was driving.

That time, it meant something. His words hit me hard. And it made me think a lot about what my days were like, and whether I was living the kind of “full days” that he was urging me to live.

Laugh, think, cry: it’s as good a guide for living as I have ever seen. Doing it really will lead to a heck of a life, as he says.

But I’m not saying it’s easy.

Even if we don’t take his advice literally, his point is worth taking to heart. We should live life deliberately.

Here’s what I mean.

Laughing every day is actually pretty easy for me. My parents loved to laugh, and they passed that on to me. Even when I was first diagnosed with cancer, I couldn’t help but laugh. It was absurd – a healthy 40 year old man with cancer? It was (and still is) ridiculous to me, and I refuse to let cancer take away my joy.

But to laugh, you have to be in the mood. If you’ve ever watched a funny movie with someone who isn’t in the mood to laugh, you know what I mean. Laughing isn’t easy for lots of people with cancer or other illnesses. It takes effort.

For me, crying was the harder thing to do. I’m a man, and a husband and father, and I’ve been conditioned to think that I am supposed to be the rock for my family. That’s not the case so much for me anymore. I give myself permission to cry now. Hearing a sad song will do it most days. So will videos of soldiers surprising their families when they return home.

And thinking? Of course we all think. But sometimes it’s easier to just not think about certain things, especially about our disease. It can be overwhelming. But not thinking sometimes means letting others make choices for us, about all aspects of our lives. Thinking guarantees that we at least let our voices be heard, about whatever the topic is.

Laughing, thinking, crying – sometimes they come easy. But not always, and not for everyone.

To live the kind of life that Jimmy V says we should live, you have to make the choice to open yourself up. To laugher. To tears. To thought.

You have to live deliberately. That’s how you end up with “something special.”

You might do one or two of those things every day – laughing, thinking, crying-- without choosing deliberately.

It takes work to choose to do all three in a day.

But what a great choice….