Wednesday, March 14, 2018

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.

Sunday, March 11, 2018

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.

Wednesday, March 7, 2018

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.

Sunday, March 4, 2018

Life Lessons

March 4 is the 25th 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 20th 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….

Wednesday, February 28, 2018

Treatments for Relapsed and Refractory FL

Every now and then, someone will publish an article that lists the treatments available for Follicular lymphoma patients. It's nice to read. Even if there's nothing new on the list, I always feel better having it all laid out in front me, knowing what's out there if (when) I need it.

Best Practice and Research: Clinical Oncology has gathered some recent articles on indolent lymphomas into its March 2018 issue. A few of them look at Follicular Lymphoma, including one of those articles that lays out treatment options.

It's called "Novel Agents for Relapsed and Refractory Lymphoma," written by Dr. Chan Yoon Cheah and Dr. Nathan Fowler. As the title says, the focus is on treatments for patients who have already been treated at least once, and either did not have a response to the treatment, or who had a response and then had the FL come back.

(Since I've already had treatment, I'm especially interested in all of this.)

The article starts out with a description of indolent lymphomas like FL -- slow-growing, often manageable, usually incurable. Ideally treatment will result in remission that lasts a long time and allows for a good quality of life.

The authors recommend that, if a relapse is suspected, a new biopsy be taken, to make sure the FL has not transformed into a more aggressive form. If it has, then there's a whole different set of considerations (and a whole different article to look at in this issue of the journal).

If there is no transformation, then there are a bunch of options: if no organs are threatened and there are no problems, then watching and waiting is OK. If treatment is necessary, they recommend that patients go into a clinical trial "whenever possible."

That's worth repeating. Patients should consider clinical trials whenever possible. If the symptoms are not life-threatening, then a trial may end up giving a response. If not, there's probably time to try something else (again, the relapsed FL isn't aggressive). And at the very least, the patient has helped us all by trying out something that might be approved for the rest of us (or might not -- that's valuable, too).

From there, the authors list some options:
  • Anti-CD20 Monoclonal Antibodies. Rituxan is the biggie here, but Obinutuzumab has been recently approved. They work on their own (I had straight Rituxan), or in lots and lots of combinations with other treatments.
  • Lenalidomide. Also known as Revimid, and R-squared when combined with Rituxan. Lenalidomide worked just OK on its own, but it has been great in that R-squared combination. I think it's one of the treatment that gets lymphoma specialists most excited. 
  • PI3K Inhibitors. Idelalisib is the one they focus on most, though they also mention Copanlisib and Duvelisib. While these inhibitors have been successful, the authors also point out some serious side effects.
  • BTK Inhibitors. Like other inhibitors, these stop (or inhibit) processes that cells go through in order to grow and survive. Ibrutinib is their main example, though there are some others in development. BTK inhibitors are another treatment type that seems to work better when it is combined with something else. (That's a big theme these days.)
  • Bcl-2 Inhibitors. Again, these treatments stop cancer cells from doing the things that the immune system can't. Venetoclax is their main example here.
  • Antibody Drug Conjugates. Monoclonal antibodies like Rituxan work by seeking out a protein on a lymphoma cell and attaching to it. A conjugate takes advantage of that -- while the antibody is attached, it delivers something else to the cell to kill it. 
  • Epigenetic Therapies. This is another group of inhibitors, thugh it targets something different than the ones above. Vorinostat is an example (though it is one that seems to work well on its onw, instead of in combination with something like Rituxan). Abexinostat and Tazemetostat are two others.
  • Immune Checkpoint Inhibitors. Nivolumab and Pembrolizumab are two examples. Another type of inhibitor, this one stops something that stops something else. The result is that the immune system is able to find and attack lymphoma cells.
  • Chimeric Antigen Receptor T Cell therapy. Also known as CAR-T, which has been in the news quite a bit lately. T cells, part of the immune system, are removed from the patients and changed so that the T cells recognize the lymphoma cells as something that doesn't belong. A very promising treatment. Read more about it at CAR-T and Follicular Non-Hodgkin's Lymphoma, the blog run by our friends Ben and Will.
Note that these are novel agents -- new ones. You may have noticed that they don't even inlcude chemotherapy, RIT, and some other treatments that have been around for a while.

A couple of trends -- lots of these treatments seem to work better when they are combined with others. And lots of newer treatments are kind of anti-chemotherapy -- instead of trying to kill the cancer cells directly, they try to to stop (inhibit) other things from happening that the cancer cells need in order to survive.

The good news with this list is that there are a lot of options being tested for us. Some of them will end up working, though not all of them will.

And it's important to remember that all of these treatments come with side effects. They might be anti-chemo, in a way, and more targeted, but that doesn't mean they won't cause some problems. Ideally, researchers are finding ways to make sure the problems aren't as bad as the solutions -- the success of the treatment is worth the side effects.

Lists like this are valuable because they give you something to talk about with your doctor, if and when the time comes to treat.

And it's worth repeating -- none of this stuff becomes available to patients until it goes through a few clinical trials and then gets approved. "Whenever possible," we should think about participating in clinical trials, and helping to make it all happen.

Saturday, February 24, 2018

Nicola Mendelsohn

This is another one of those Follicular Lymphoma news stories that a few of you have told me about. I've been thinking about it for a few weeks now.

On February 4 (World Cancer Day), the Sunday Times published a piece by Nicola Mendelsohn.

She is Facebook’s Vice President for Europe, the Middle East, and Africa – someone with a loud voice when it comes to spreading the word about something. In the piece, she describes her experiences as a Follicular Lymphoma patient.

I know that story.

As many of you know, I was diagnosed with Follicular Lymphoma a little over 10 years ago, and reading about her experiences was like reliving my own past.

She writes, “It was a terrible shock. I didn’t even feel ill….So when the doctor told me, I just kept thinking: ‘But I’m fit. I’m young’.”

Yup. As many of us know, lots of FL patients have no symptoms when they are diagnosed. At most, maybe a lump that won’t go away, that gets worrisome after a few weeks or months. Like Mendelsohn, I found a lump near my hip bone. And like her, I was in the best shape of my life at the time.

And like Mendelsohn, I was young – 40 years old (she was 46) – diagnosed with a disease that usually gets diagnosed in people in their 60s.

“[My husband Jon and I] gathered our four children — aged 13-20 — together and sat them down to explain my condition. Zac is our youngest and his first question was: ‘Are you going to die?’ That’s always the thought that comes into your head when you hear the word ‘cancer’. It is not a conversation I could ever have imagined having with them, not even in my worst nightmares, until it hit me in the face. It was the hardest moment of my life.”

Yup to that one, too. My kids were younger than Mendelsohn’s – 6, 8, and 10 – but telling them was also the hardest thing I’ve ever had to do in my life. Mine didn’t ask about death. They didn’t say anything. But I had my arms around my boys, and I felt my oldest child’s body tense up as I said the word “cancer.” It relaxed only when I mentioned the name Jon Lester, a pitcher for the Boston Red Sox, his favorite team, who had come back from aggressive Lymphoma a few months before.

There are other similarities between us, too. For both of us, our spouses have been our greatest gift. We both chose to watch and wait, holding off on treatment until symptoms get worse.  We are both able to enjoy a good quality of life. We both quickly found how important it is to have a community of people who understand what we’re going through (for Mendelsohn, that came, naturally, through a Facebook group, one that I have also been a member of for a while).

But the thing that connected with me most was the title of her article:

“My Life Sentence.”

Follicular Lymphoma is, as we all know, incurable.

About a month ago, I celebrated the 10th anniversary of my diagnosis. When I was diagnosed, I read that the median survival rate was 8-10 years for Follicular Lymphoma patients. So 10 years was always kind of a special milestone for me. It was always something to reach for.

Many cancer patients hit a 10 year anniversary, and it’s a pretty clear sign that the cancer isn’t coming back. Not so much with an incurable cancer like Follicular Lymphoma.

10 years with FL requires a different kind of celebration. It’s not so much celebrating the day of the diagnosis.

For me, that day was about celebrating the 3,653 days since my diagnosis.

And it was celebrating all of the days that are to follow.

I guess that’s two more ways that I see my story in Mendelsohn’s.

The first is our shared desire to use our diagnosis to help others. For Mendelsohn, that means using the power of Facebook and its communities to bring people together for education and inspiration. For me, it’s the same thing, using my blog to listen, respond, help, and inspire.

The second is our attitude.

“Sometimes, when people receive a diagnosis like this, it can really change them: who they are, what they stand for, the choices they make. That hasn’t really happened to me. I’m on a different path now, but I’ve always been an optimist — someone who cherishes life and is grateful for what I’ve been given. Now I just feel even more grateful.”

It can be hard some days to feel optimistic and grateful. And that’s OK. That’s one of the things that online communities can be good for – to get you through the hard days.

But other days, you wake up and put your feet on the floor and try to be grateful for day number 3,654. You hug your spouse and kids a little tighter. You try to find ways to make your small corner of the world a better place. You cherish life.

So thank you, Nicola Mendelsohn, for sharing your story. For being a model for how to face adversity. For having a voice and using it to help us. I’m sorry you had to join this crappy club. But I’m really glad to have you here.

Tuesday, February 20, 2018

New Stanford Immunotherapy

A few of you have left comments or sent emails about this news story, and I'm finally getting around to writing about it. (I've been unusually busy these days. It's a good problem to have -- it means I'm healthy enough to be busy.)

The news comes out of Stanford University. The press release from Stanford is called "Cancer 'Vaccine' Eliminates Tumors in Mice."

This is one of those pieces of news that gets reported in a lot of places and gets people very excited. But those kinds of stories (for those of us who have been through this before) usually mean we need to slow down and read carefully and not get too excited.

The study being reported deals with an Immunotherapy method that seems simpler and less expensive than some others. (I'm thinking about CAR-T, for example.) In this method, two very very small amounts of two agents are injected directly into tumors. (In the study, which used mice, there were tumors in many different locations in the body, not just lymphomas.)

And these are really small amounts -- measured in micrograms (a microgram is one millionth of a gram). That's so small I can't even think of a way of comparing it.

The two agents that are injected are, first, a CpG oligonucleotide, which is a short piece of DNA. This works with cells nearby to hep activate a receptor on T cells called OX40. It's basically sending a  signal to cells that they need to get ready to attack. The second thing is an antibody that latches on to the OX40 on those T cells. When that happens, the T cells (part of the body's immune system that attack invaders) now know which cells to attack -- that antibody has told them what to look for.

The T cells do their thing and find and attack cancer cells. But even better -- T cells don't stay in one place in the body. They move around and look for more of those same cells to attack. So if there are tumors is in more than one place, the activated T cells will find them and attack them, too.

The T cells are targeted -- they will only look for the cancer cells they are told to look for. So when the researchers used a mouse with both Lymphoma and colon cancer, but only set t up for the T cells to look for the Lymphoma cells, the colon cancer cells were ignored.

The results were impressive. 87 of 90 mice had their cancer cells wiped out. The other 3 were given a second round, and that did the trick.

the results were good enough to have a phase I clinical trial start last month. While the mouse study involved lots of types of cancer, this trial will look at 15 Lymphoma patients.

There are lots of reasons to be hopeful about this. Immunotherapy is big these days, and this treatments seems to work in a way that makes sense -- finding ways to stimulate the immune system to do its job on cancer cells, which normally find ways to fool the immune system. It also has Dr. Ronald Levy as its senior researcher (he's a genuine Lymphoma Rock Star -- he played a big part in developing Rituxan).

But the usual cautions apply here. It was tested on mice, not humans. Obviously, there are going to be some differences.

But that's why we have clinical trials. A phase I study will see if it really works the way we think it will (and hope it will). It will give us a sense of safety -- what kinds of side effects that might come from this treatment, short term and longer-term.

We know that lots of promising treatments sound great when they are given to mice, but never make it to phase 2 or 3, let along to approval.

The good news is, even if it doesn't work, we'll learn something from that and try again.

(I know, I'm an optimist.)

Definitely something to keep an eye on.

(And again thanks to everyone who sent me the link.)