Wednesday, November 15, 2017

Some Thoughts About Overall Survival in FL

This is sort-of related to ASH, though it isn't looking at one of the abstracts, like I usually do this time of year.

I've been reading the ASH abstracts (over 200 of them) looking for the ones that I find interesting or worth talking about in some way. And I came across a few that mention OS, or Overall Survival for Follicular Lymphoma. It's worth talking again about OS and what it means.


The ASH abstracts are basically summaries of what the presentation is going to be about. They mostly start off with an Introduction -- some description of the general topic of the presentation. The rest of the abstract gets into the specifics. Some of the Intros start off really general, describing what Follicular Lymphoma is, and, if it's appropriate, giving some statistics about things like OS.

As I was reading, one of the things that I found really interesting was the different ways that various researchers talked about FL and OS. For example, these are from 4 different Introductions:

  • "Most patients experience an indolent disease course, with median survival of over 15 years."
  • "Follicular lymphoma (FL) is the most common indolent lymphoma with a median survival approaching 20 years."
  • "Follicular lymphoma (FL) is usually an indolent malignant B-cell lymphoma with median survival now approaching 20 years in the rituximab treatment era."
  • "Despite an indolent course, it remains an incurable disease and the overall survival (OS) is 70-80% at 8 years in the rituximab era."
  • "The clinical course of follicular lymphoma (FL) is characterized by recurrent relapses and progressively shorter remissions, with many patients surviving beyond one decade from initial diagnosis."
Now, to be clear, these are written for other oncologists and hematologists -- experts in blood cancer. And, to be clear, they have reasons for presenting these numbers the way they do. It helps set up the point they want to make about the research they did and why it's important. And those numbers all mean basically the same thing, if you look at them closely enough. But it's strange that they are all presented differently.

And I'm looking at these numbers as a patient. Patients read numbers differently than doctors do.

I did a quick Google search, and it showed me various sites (all up-to-date and reputable) that give the median OS for FL as 19 years; 14 years; over 20 years; "historically 8-10 years" but longer recently; and "Around 10 years," but ranging from 1 year to 20 years.

It's all very confusing, isn't it?

And what makes it worse is that, especially for someone newly diagnosed, survival numbers are really, really important. It's one of the first questions we ask -- "Cancer? Oh no! How long do I have?!"

Unfortunately, the media OS isn't going to give you an answer.


So what's the deal with Overall Survival?

First of all, the reason the ASH abstracts are kind of fuzzy is that there isn't really agreement on what the median OS is for Follicular Lymphoma. I have read that it's because many patients live for a long time. It's hard to calculate a median survival (a measure of when people die) when people are staying alive. So that's a good thing.

The numbers are also kind of fuzzy because different studies have come up with different figures. There are a lot of factors that can mess with that number -- the age of the patients, the treatments they have had, how long ago they were diagnosed, and how treatments have improved recently. So it's easier to say "approaching 20 years" or "over 15 years" or (to be especially vague) "beyond one decade" than it is to give a definite number.

But, as patients, none of that really eases our minds. There's a big difference for us between 10 years and 20 years.

So here are some things to keep in mind about Overall Survival, especially if you're one of those folks who was recently diagnosed, or who obsesses over numbers. I hope it eases your mind just a little.

First, OS is usually expressed as "Median Overall Survival." And "median" matters. It doesn't mean "average." In statistics, the median is the middle of a group of numbers. So if the median OS for Follicular Lymphoma is 20 years, and they came to that number by looking at 1000 patients, that means that 500 of them will live for less than 20 years, and 500 will live for more than 20 years. On the "more" side, that could go on for a long, long time -- 21 years, 25 years, 50 years. There is no upper limit. A median OS of 20 years does not mean you have only 20 years to live. It meas you have a 50% chance of living longer than that -- maybe much longer.

Second, "Overall Survival" is just that -- the number of patients who have survived overall. It measures death by any cause. That includes lymphoma-related deaths, but also death by heart attack, or by snake bite, or by getting hit by a double-decker bus. It's easy to think of that number as being just about lymphoma, and that makes lymphoma seem so much scarier. But OS includes any reason for not surviving.

Third, keep in mind that the average age at diagnosis for Follicular Lymphoma is somewhere in the 60s. That puts the OS number in a different light, especially for those of us who were diagnosed at a younger age (like me, diagnosed at 40). Right now, in the United States, a male who is 60 years old has a life expectancy of 83.3 years. He will live, on average, another 23 years. Compare that to the OS for a patients diagnosed at 60 with FL: about 80 years. Not a huge difference. In fact, you will sometimes see discussions of FL survival point out that it is "approaching the general population."

And keep in mind that the numbers are different for different age groups. People under 60 (I have read) have a higher OS than the overall median. We can expect, statistically, to be on the part of the scale that goes way beyond 20 years.

One more thing: this OS number changes. All the time. It has risen steadily in the almost 10 years that I have been a patient. I remember a loved one emailing me and my wife in a panic because he'd looked up Follicular Lymphoma and Wikipedia said the median OS was 8 to 10 years. So it has about doubled since then, thanks to better treatments and better ways of measuring. I expect it to go up some more in the next 10 years (and I expect to be around to watch it).


Here's the point I want to make:

Try not to obsess about numbers.

I know it's hard. Numbers seem so sure, and so final, and so unchanging. 2 + 2 always equals 4. In our emotionally-charged brains, it's easy to go from that to thinking "and therefore, I have only 20 years to live" (or 14, or 8 to 10).

Numbers aren't as sure as they seem to be. The huge range of OS statistics out there should prove that. And if experts are only willing to give fuzzy numbers, that should make it even more likely.

A median or an average says nothing about each of us as individuals.

The best we can do is live a good life, enjoy every day, be kind to one another, make the world a better place, learn as much as we can about our disease, and be active in the decisions that get made about our healthcare.

And have dessert.

So go do all of those things.

Friday, November 10, 2017

ASH Preview: Surveillance Scans for Follicular Lymphoma

Surveillance Imaging is common in Follicular Lymphoma -- CT or PET scans after treatment that are meant to find out whether or not the FL has returned.

They are common, but controversial. With every scan, you get radiation. In fact, a CT scan exposes a patient to about 200 times the radiation of a chest x-ray. The question is, is it worth it? Will the scan catch the cancer before the doctor or patient can? I have read (and I cannot find or remember the source) that about 80% of recurrences of FL come from the patient reporting symptoms, not from routine scans. Is that true?

The ASH presentation "Surveillance Imaging during First-Remission in Follicular Lymphoma Does Not Impact Overall Survival" adds some data to answer that question.

The research involved 148 FL patients who had responded to a first treatment. The were observed for a median period of just under 5 years. Of that group, 55patients then had a relapse, discovered either by a surveillance scan or by clinical examination (the presence of symptoms, an abnormal exam, or by lab findings).

Of those 55 relapses, 35 of them (64%) were detected clinically, and 18 of them (33%) were asymptomatic but were found during a routine scan. There was no difference in Overall Survival between the two groups.

Breaking things down even more, the researchers looked at all of the scans for the 130 FL patients who had routine scans at their cancer center (including those who didn't relapse). 584 of the scans were part of routine surveillance for patients without any symptoms, with 68 of them for patients who were thought to have relapsed (even though they were asymptomatic). Just 22 of those "concerning" scans showed that there was FL. So only 3.8% (22 out of 584) of the scans for patients who didn't have symptoms resulted in a positive diagnosis.

Their conclusion: Only 1 in 25 scans results in a confirmed diagnosis for Follicular Lymphoma. With no Overall Survival benefit from doing the scans, there has to be some question about whether it's worth it. They recommend a larger study to see if the results can be confirmed.

As a patient, I have a mixed history with scans, but I now firmly believe that if there's no reason to do a scan, they shouldn't be done.

After I finished my Rituxan, I had a PET to confirm the results (this is common and NOT controversial). My dear Dr. R put off doing another scan. At every visit, he'd say, "We could do one, but there's no reason to, so let's hold off. Maybe next time." After about four years, I asked for one. I wanted to satisfy my own curiosity, mainly. It's hard writing about cancer so much and not knowing what exactly is going on inside your own body.

So I had the scan. It confirmed the presence of some FL, but not much. I was satisfied.

A couple of years later, Dr. R moved out of state, and I was switched to Dr. K.

Dr. K had a bad habit of not listening to me. He kind of had a set speech for every visit, and any time I tried to break in ("Yes, I do know what white blood cells are...."), he would steamroll over me. Very frustrating. I don't like it when I'm not being listened to.

So after a couple of visits, he said he wanted to do a PET scan. I asked if there was a concern.

"No, no concern. Just for a baseline. I don't think we'll find anything, to be honest."

"Then why do it?" I asked.

"Just so we can see what's there. I don't think we'll find anything."

"Then why do it?"

We did this a couple more times, and then the visit was over. His assistant noted that Dr. K wanted to schedule a scan.

"I'll get back to you on that."

Dr. K retired before my next appointment. I still haven't gotten the scan he wanted. It made no sense to me to get one when even the doctor didn't think it would find anything, Why take on all of that radiation for no reason?

The evidence from this research certainly seems to show that I was right.

(Oh my gosh, do I love being right!)

I understand the need to want to confirm that things are still OK, and want a clear picture (literally) that they are. It's the same as any kind of watching and waiting -- we're relying on our own understanding of our bodies to make sure everything is, and sometimes it's helpful, emotionally, to have science confirm that understanding. I get it. And I would never judge any Follicular Lymphoma patient for wanting a scan because it makes her feel better. that matters, too.

But, looking at things long-term, we also need to trust that clinical exams will find bad things, and that includes our own self-examination of symptoms.

Don't be bullied into a scan. Get it if it's your choice, and you understand the risks.

Tuesday, November 7, 2017

ASH Preview: Follicular Lymphoma: The Good, The Bad, and The Grade 3

OK -- time to start looking at some ASH abstracts.

In the comments in my last post, Dan suggested I look at the abstract for a session called "Effect of Histologic Grade on Clinical Outcomes of Follicular Lymphoma: Prolonged Progression Free Survival of Grade 3 Follicular Lymphoma in the Rituximab Era."  I had my eye on this one because a few people were discussing it in the support group I've been in for years. ( I rarely post anymore, but I check in every day. the link is on the right under "Sites I Like.")

There's a lot going on in this abstract.

The researchers are interested in Grade 3 Follicular Lymphoma, and how it compares to grades 1 and 2 in terms of outcomes. (I was diagnosed as grade 1, with some grade 2.) In general, a higher grade means the cells are expected to behave more aggressively. The grade is determined by how many large, aggressive cells are visible by a pathologist in a particular area. (See for more on this.)

The important thing is, higher grade = more aggressive type of FL. It's more complicated than that for lots of reasons; the Lymphomation link gets into some of that.)

Grades 1 and 2 are usually considered less aggressive. Grade 3 used to be just one grade, but now it is usually broken into grade 3A (which behaves like grade 1 and 2) and grade 3B (which behaves more like Diffuse Large B Cell Lymphoma, a more aggressive type).

I'm going to assume that anyone reading this knows their (or their loved one's) grade.

The researchers wanted to know the difference in outcomes for the different grades. It seems reasonable to think that grade 3 would probably have worse outcomes, right? We've all been told about Transformation, and we're scared of it. Our slow-growing lymphoma becomes fast-growing, and that's bad. Aggressive must be bad. right?

Turns out that's not the case.

The researchers looked back at 227 patients who were diagnosed with FL between 2002 and 2014. 27% of the patients has grade 3 FL (either 3A or 3B) and the rest had grade 1 or 2.

The results: patients with grade 3 FL had a higher rate of Transformation (30%) than grade 1 and 2 (12%).

But there was no real difference in Overall Survival between the groups.
Grade 3 had a higher Progression Free Survival (61% after 5 years, versus 41% for grades 1 and 2).
The grade 3 group had a higher PFS when they limited it only to those who had immunochemotherapy with anthracycline (like R-CHOP). And when they isolated out the grade 3A patients, they had a higher PFS, too.

Here's their conclusion: "In this retrospective study of outcomes of follicular lymphoma in the rituximab era, we observed that patients diagnosed with grade 3 FL have better PFS than patients diagnosed with lower grade FL. This improved outcome appears to be independent of the choice of initial therapy, with an apparent plateau in the risk of relapse of patients diagnosed with grade 3A FL, suggesting a subgroup of these subjects can receive front line treatment with curative intent."

In other words, their data suggests that initial treatments for some patients with grade 3A might last long enough that it could be considered a cure.


I'm guessing there's going to be some commentary from experts on this one in the next few weeks, as we get closer to ASH. It's surprising, but it makes sense.

DLBCL is an aggressive cancer, but it's curable, unlike most Follicular Lymphoma. So a grade that has more aggressive cells, and that behaves like an aggressive lymphoma, would more likely to be curable.

From a patient perspective, though, it brings up an interesting issue (one that was touched on the the support group discussion).

When it comes to Lymphoma, what's "good" and what's "bad"?

I remember, years ago, in that same support group, a discussion broke out about indolent and aggressive lymphomas. A lot of us have had people say to us, "Follicular Lymphoma? Well, at least you got the good one," or "If you're going to get one, this is the one to have."

Is it?

The folks in the support group had a debate over which was "better" -- the aggressive one that is potentially curable, or the indolent one that you might live for years with.

The aggressive one is scary. It grows quickly. You see the numbers getting larger by the week.

But R-CHOP or B-R or a stem cell transplant might cure it. That's good.

But it might not. That's bad.

An indolent lymphoma like Follicular might go years without needing treatment. That's good.

But those years aren't always happy years. Every bump or lump or lingering cold or tingling foot or swollen ankle or pulled side muscle means panic for a few days until it gets better or the oncologist will see you and check it out. That's not so great either. It takes a toll, emotionally and physically.

(As you know, I think FL is as much an emotional disease as a physical one.)

If I could go back 10 years and choose one over the other, which would I choose?

I honestly can't say.

The lesson, I guess, is that as patients, we can't assume a diagnosis, whatever it is, is better or worse than another. Our job is to understand what we have, educate ourselves enough to be clear about our options, and insist on an honest and open conversation with our doctor in which our voice is respected.

More ASH previews to come. I hope they aren't all this emotionally exhausting.....

Friday, November 3, 2017

ASH Abstracts Are Here!

Last night, I saw my first ASH abstract linked on Twitter. You know what that means -- ASH is coming!

It's the Cancer Nerd Christmas!

If you're new to this, ASH is the American Society of Hematology, a large professional group for blood cancer specialists (and specialists of other blood disorders). Their annual meeting takes place around the first week of December every year. This year, it's in Atlanta, Georgia (lovely city) from December 9 to 12, and it is often the place where researchers will talk about the work they are doing, sometimes releasing or updating results from clinical trials.

A few weeks before the meeting, the chatter starts. Last night, I saw an abstract on Twitter. This morning, I had a couple of emails in my inbox from publicists who were hinting that good things were going to be announced at the meeting.

It really is like Christmas, with moms and dads telling kids that Santa Claus will be coming soon. Only it's researchers and public relations offices, and instead of getting me excited about video games and dolls, they're talking about immunotherapy combinations and cell-signaling pathways.

Tome, that's just as much fun. And even better, I don't need to behave myself for the next 6 weeks because Santa might be watching.

I have only taken a very quick look at the abstracts for Follicular Lymphoma (you can see them here if you're curious), but it looks like a lot of updates to data from recent clinical trials. I see a lot of Rituxan-focused abstracts, too, and Bendamustine keeps coming up. There will be more updated data for Copanlisib, and more results for trials involving Obinutuzumab, and for Lenalidomide. And it looks like a few abstracts on Transformation.

There's going to be a lot to go through.

My plan, as usual, is to sift through abstracts and write about things that I find interesting. It's pretty subjective -- some of the things I find interesting aren't necessarily that ones that the actual experts are excited about.

It's also important to remind you that I'm not going to be at the meeting. I'm just looking at the abstracts -- the summaries of what's going to be talked about. Sometimes what actually gets said is more important than what gets sent in weeks before the meeting.

I'll also keep an eye out on Twitter and elsewhere for what some of my favorite blood cancer specialists are saying about the meeting, and what has them excited.

And I'll keep an eye out for press releases and articles that come out during the meeting and soon after, bragging about the success of their presentations. (And many of them will be worth bragging about.)

So look for lots of stuff about current research over the next few weeks.

I'll post as often as I can. Looking forward to it. Merry Cancer Nerd Christmas!

Tuesday, October 31, 2017

What Breast Cancer Awareness Month Can Teach Us

October is coming to a close, and that means Breast Cancer Awareness Month is ending.

I've always had a funny relationship with Breast Cancer Awareness Month, or "Pinktober" as it is sometimes called. On the one hand, I really hate all of the pink that comes with it. My kids' old school did a "Pink Day,"and my town painted one of its police cars pink. Plus there are all of the pink-wrapped products at the grocery store.

Part of it is jealousy. I'd love it people cared about Lymphoma as much as they seem to care about Breast Cancer.

But I also recognize that there is some good that comes with "awareness."

I wrote about this is a piece I had published on The Mighty a few days ago. It's called "What the Rest of Us (Cancer Patients and Survivors) Can Learn from Pinktober." I invite you to take a few minutes to read it.

Ultimately, the lesson for all of us is that if we want others to be "aware" of our cancer, then we have to be the ones to make it happen. And that means being open about what we experience, encouraging people to do things to prevent cancer, to get themselves tested (and to do self-exams), and, if they are unfortunate enough to get a cancer diagnosis, to educate themselves about their disease.

So if you are like me, and you got a little frustrated at all of the pink from the last month, try to see some good in it. There are absolutely people who exploit Pinktober for their own gain, and that's a shame. But -- big picture -- talking about cancer is better than not talking about it.

I'm looking forward to another month of learning and writing.

Saturday, October 28, 2017

Follicular Lymphoma: Changes in the Treatment Landscape

Thanks to William, who sent me the link to an hour-long video from OncLive. I thought it was a compilation of some shorter videos, and I was going to ignore it, but I'm glad William alerted me to it. It features some great Lymphoma specialists, and is worth watching.

The video is aimed at oncologists, to give them a sense of the state of the art when it comes to treating Follicular Lymphoma. It's called "Follicular Lymphoma: Changes in the Treatment Landscape," and it features Dr. Bruce Cheson of the Georgetown Lombardi Comprehensive Cancer Center, Dr. Nathan Fowler of MD Anderson Cancer Center, and Dr. Anas Younes of Memorial Sloan Kettering Cancer Center.

That's some serious Lymphoma Rock Star stuff.

[I might go back to my idea from a few years ago of creating trading cards with Lymphoma Rock Stars on them. You'll get a free pack with every Rituxan infusion. Trade with your friends!]

The Rock Star Doctors cover a lot. From my perspective as a Cancer Nerd, it's all fascinating to me. Their subject is how treatments are changing, so they go into a lot about specific treatments, and the clinical trials that they were involved in, so it can kind of technical. But I'm OK with that.

Aside from being Cancer Nerd, though, I'm also a cancer patient, and that's different. It's one thing to gaze lovingly at a video, and another to think about how it all affects my actual life as someone with Follicular Lymphoma.

So these are the things that stood out for me as a patient:

First, they open the discussion by talking about some of the "scoring systems" that are used to measure prognosis. these are things like FLIPI and FLIPI-m7. The problem with these scoring systems, as they point out, is that they tell us a lot about groups of patients (they were created by looking at data from large groups), but don't say anything about individual patients.

Sometimes, as patients, we look at "scores" like FLIPI, and the numbers seem so definite, that we assume they will predict our futures. They won't. They can't. It's just not what they are meant to do. I'm happy that these three make that point -- and I hope that message gets through to oncologists who may use those numbers without explaining their significance to patients.

Another topic that thrilled me as a patient was their discussion of Subcutaneous Rituxan. All of them were thrilled with the amount of time that subcutaneous Rituxan cuts out from the patient's visit. It can go from about 6 hours (roughly how long my first Rituxan infusion took) to about 10 minutes. That's a huge improvement on Quality of Life. Dr. Cheson asked an important question -- how accepted will this be? He hinted that some doctors might stick with the IV version if Rituxan, because it might generate more revenue. That would be pretty horrible, putting profits ahead of patients. It's great that this discussion was being aimed at working oncologists. I think some of them can use the reminder that our Quality of Life matters, especially if some of us will be living with FL for years and years.

I'm happy that the good doctors made that point to lots of other doctors who might watch.

Another interesting exchange: the possibility of a cure. Dr. Fowler first brings this up, and Dr. Cheson asks if he "used the 'C' word" (and then makes it clear that it was he who has encouraged Dr. Fowler to think in those terms). The two are clearly more open to the idea of an eventual cure for FL than Dr. Younes, as least at this point.

But I like that, too -- that mix of optimism from Fowler and Cheson, balanced with a little skepticism from Younes. I think that's about the right mix -- 2/3 optimism about our future and all the great stuff that is happening in the FL treatment landscape, with 1/3 reminind ourselves that there's a long way to go.

Which isn't to say that Fowler and Cheson are blindly optimistic, or that Younes isn't also enthusiastic about things. Because there is plenty enthusiasm and plenty of realism from all three of them.

In fact, one of the really great things about the video (I'm speaking as a Cancer Nerd again) is the way they consider the many clinical trials and treatments that they look at -- with enthusiasm and realism. They're all hopeful about the future, but they know there's a way to go. These treatments are going to help a lot of people, but we're not there yet.

Another Cancer Nerd thrill for me: at the end of the discussion, they discuss how the community can try to prioritize certain treatments or combinations of treatments. there are, for example, a fairly large number of BTK inhibitors. It's an excellent target, but maybe putting resources into other targets would be good, too. There's certainly a patient aspect to this as well -- there are only so many patients who are willing to participate in trials, so a better focus would be more more efficient. Also, doing more to consider the safety of some combinations would also be good. And for that matter, maybe greater incentives for patients to participate in trials would help a lot.

[And for my CAR-T friends, going back to a discussion we had a few weeks ago in the comments -- certainly seems like CAR-T is going to be focused on patients who have had 4 or 5 previous treatments already. Cost and toxicity are the issues for now, though maybe that will change.]

So, once again, this is really great video, with some Rock Star panelists. (I'm too much of a Fanboy, I know, but this was like watching Glengarry Glen Ross or Doubt -- a bunch of Oscar winners and nominees doing their thing.)

Sunday, October 22, 2017

Awesome Video on the Importance of Educating Yourself

I want to recommend another great Lymphoma video for you. This one is great because of the star -- me!

WEGO Health asked me to make a video about the importance of doing research and educating yourself -- definitely something that I'm in favor of. The video is being used to introduce a WebMD slide show about a side effect of Hodgkin's Lymphoma treatment. (Yes, it's not the same as Follicular Lymphoma, but that's OK -- as I say in the video, doing research is important no matter what lymphoma subtype you might be living with.)

You might remember that WEGO Health are the folks that sponsor awards for online health advocates, and I was nominated for a couple of them (best blog and best kept secret). Alas, I didn't win, or even make the final five for either category. But that's fine -- it was nice to be nominated, and be listed among all of those great online health advocates. Thanks to those of you who voted for me.

I know some of you voted for me just so you could go to the page and see my picture. Well, here's your chance to hear my voice, too.

If you've been reading the blog for a while, my message in the video will be familiar.

There were 3 things I wanted to make sure I said: 1) There is a lot of information online, and it's important to find good information that is evidence-based, backed up by science; 2) Cancer is an emotional disease as well as a physical one, and doing research can help with that, too; and 3) doing research gives me a feeling of control over things that seem uncontrollable. I'm happy I was able to get all three of those messages in.

And I think I seem waaaaay more serious in this video than I usually am in real life. But that's because I did this in about 30 takes (I went too long, or the dog would make noise, or I'd forget what I was going to say, etc, etc. There are lots of frustrated bad words in the blooper reel). So by the end, I was focusing really really hard on just getting it right. That's not me being serious so much as just really focused.

The video is on the WEGO Health Facebook page. You can watch it even if you don't have Facebook.
The full video is here:

The short version (just the invitation to click the link to the slide show) is here:

(For some reason, the shorter version is way more popular. I guess people get sick of listening to me. I'm used to it -- I have three kids.)

It was fun making the video. I might do more of it soon. Thanks, WEGO Health, for the opportunity.

Thursday, October 19, 2017

CAR-T Approved for Lymphoma

More good news for us -- the FDA has approved a CAR-T treatment for some Follicular Lymphoma patients.

(As usual, when it comes to CAR-T news, Ben beat me to the news. I just learned that he is a fan of the New York Yankees -- rivals to my beloved Boston Red Sox. I still like him anyway, and I'll keep sending you to his blog for everything you want to know about CAR-T and Lymphoma.)

The treatment is called axicabtagene ciloleucel, or axi-cel, though it will probably known to patients as Yescarta (to help you remember: Yes! CAR-T! Ahhhhhh!). The approval came from the results of the ZUMA-1 clinical trial, which involved patients with refractory aggressive B cell lymphomas.

That's important to remember. For now, anyway, the approval is for a very specific group of Follicular Lymphoma patients -- those with Transformed FL. There are other types of aggressive B cell lymphomas, too, who meet the approval criteria. But it's a big step for all lymphomas.

As a reminder, CAR-T stands for Chimeric Antigen Receptor T cell therapy. In the procedure, a patient has T cells removed from her blood. T cells are a type of white blood cell, part of the immune system, whose job is to attack invaders like viruses and bacteria. But they don't attack cancer cells. With CAR-T, after the T cells are removed, they are genetically engineered so that, when they are put back into the patient, they do recognize the cancer cells as invaders, and they attack. T cells have a memory, so if the cancer cells come back, they should be able to find them and attack again.

The ZUMA-1 trial involved 101 patients with several types of aggressive B cells lymphomas, including Transformed FL. The results were great -- 82% had a Response, including 54% who had a Complete Response. Six months after treatment, 36% were still in remission.

There are some side effects, of course, though researchers are looking into ways to recognize the most dangerous ones early and control them.

But there may be some other problems with this treatment (which I have seen coming up since the approval news).

The first will be the cost. This is an expensive treatment -- about $373,000. Granted, it's a personalized treatment -- each patient will have her own cells removed, manipulated, and put back, so it's not like it can be manufactured in large quantities. But it's still a lot of money.

The second will be the limited number of patients who have conditions that it has been approved for. It's pretty clear that only certain patients are approved for this (as is the case with any FDA approval). But Dr. John Leonard had a good point on Twitter last night. He said "I expect MDs to spend much more time explaining to lymphoma patients why they are not CAR-T candidates than managing the very few who are." This is likely to get a lot of attention (which it deserves), but won't be able to help a lot of patients -- yet. The manufacturer is developing CAR-T treatments for other types of solid cancer. The ZUMA-2 trial is looking at this treatment in Mantle Cell Lymphoma patients. ZUMA-3 is for Acute Lymphoblastic Leukemia patients.

It keeps going. ZUMA-5 is the trial for indolent (slow-growing) lymphoma patients, like those who have Follicular Lymphoma. It will look at 50 patients with indolent lymphoma whose disease has relapsed within two years of initial treatment, or had a second (or greater) treatment stop working, or who relapsed after a transplant. The first patient to get treatment in that trial got it in August.

We have a lot to look forward to.

(And I don't just mean next spring, when baseball starts up again for some of us.)

Sunday, October 15, 2017

EJM: New Paradigms for FL

Let's keep this theme going. The European Medical Journal published an edition that looked back at the European Hematology Association conference from last June.  In all of my reading about Follicular Lymphoma, it seems like the kinds of research that gets done in the U.S. is the same as in other parts of the world, more or less, but I enjoy getting a different perspective on things.

One section of the journal is called "Shifting Treatment Paradigms in Non-Hodgkin Lymphomas," and in that section is a piece called "Follicular Lymphoma: Strategies in the Era of New Targeted Therapies." [The link should take you right to the article on FL, but if it doesn't, scroll to page 36.]

The FL article is written by Professor Dolores Caballero from University Hospital Salamanca in Spain. She gives a sense of the current state of treatment and its results. In a nutshell:

The median Overall Survival for FL is about 15 years. [Remember "median" means half of patients will survive less than that, and half will survive more. Also remember that most FL patients are diagnosed in their 60's; the media OS for younger patients is much longer than 15 years.] Common options are watching and waiting, straight Rituxan, and immunochemotherapy (usually Rituxan + CHOP, CVP, or Bendamustine.)  Patients with no symptoms often get W & W or Rituxan; patients with a higher tumor burden often get R + chemo. Some benefit from Rituxan Maintenance. Some more aggressive approaches seem to improve Progression Free Survival (how long it takes until the disease starts to get worse), but don't improve Overall Survival.

That about sums it up, right?

Prof. Caballero continues: While something like R-CHOP might increase PFS, it also comes with side effects that affect Quality of Life. Traditional chemotherapy attacks healthy cells as well as cancer cells. What we need (and what we have) are treatments that focus on the cancer cells and leave everything else alone. This should result in fewer side effects. And since FL is a heterogeneous disease -- it's a little bit different for everyone -- it would be good to have a bunch of options.

And that's what we have. Prof. Caballero gives a brief discussion of some of the targeted options available, and how well they have performed in trials. These include Obinutuzumab (combined with chemo, it had a higher 3 year PFS  than Rituxan + chemo), Idelalisib (a PI3K inhibitor, which seems to work best with patients who are high risk and have had several prior treatments), Ibrutinib (a BTK inhibitor with high response rates), and Lenalidomide.

Lenalidomide gets the most discussion here (it's not a long article, but it gets about 4 paragraphs). An immunomodulatory agent, it has been combined with Rituxan to create "R-squared" (Lenalidomide also goes by the name Revlimid). It's a combination that has had lymphoma specialists very excited for a few years.

Dr. Caballero finishes by pointing out that next generation treatments will combine biologic and targeted agents, in ways that are based on individual patient needs. But we need to learn more about biomarkers -- those clues that help predict which patients will respond to which treatments even before they try them.

So, looking at the trends here, and comparing what a European expert is excited about to what American experts seem excited about, I'd say Lenalidomide is near the top of everyone's list. More targeted treatments like inhibitors are also up there. And there's plenty of buzz about CAR-T.

The big lesson I'm taking away is that we have a lot of options, and more on the way. And if you think about some of the combinations that are being tested, that's even more still.

The future looks bright, on both sides of the world.

Tuesday, October 10, 2017

NCCN Congress on Hematologic Malignancies

A few days ago, the NCCN Congress on Hematologic Malignancies took place in San Francisco. The NCCN is the National Comprehensive Cancer Network, a group of cancer research centers best known for their guidelines for cancer treatment. They have a number of meetings every year for different cancer specialists, to give updates on different sub-types. Of course, Follicular Lymphoma was one of the topics of discussion.

I wasn't at the Congress, but OncLive has a couple of articles (one with a video) describing the FL session. (OncLive has a whole series of pieces on the sessions for different blood cancer subtypes, and they posted them almost immediately. OncLive has always been good, but they are just nailing it lately. My thanks to them.)

(While I'm at it, I just want to say that I would love to actually be at all of these meetings, like ASH and ASCO and NCCN and the rest. I wish I had the time and money to go. Maybe some day after i retire.)

(And yes, even though I'm 15 or 20 years from retiring, I do plan to be around until then -- and longer after that.)

Anyway, both articles focus on Dr. Jane Winter from Northwestern University in Chicago. (I believe she was the expert who presented on Follicular Lymphoma.)

The first OncLive article gives an overview of the session. Some of the issues she covered:
  •  Stage 1 FL can sometimes be treated with radiotherapy -- traditional radiation. A PET scan can help identify if this approach will be helpful. Up to half of stage 1 patients can possibly be cured with radiotherapy. Unfortunately, fewer than 1/3 of patients who could benefit from this treatment actually get it. (Don't know why, but I suspect that the difficulty of diagnosing at stage 1 might be part of it -- for most of us, we don't actually notice symptoms until stage 3 or 4.)
  • For many patients with stage 3 or 4 disease, watch and wait is still an option. The signals that it is time to treat? Symptoms start to show up, threats to organs [that's what happened with me -- swollen inguinal nodes started pushing on things], cytopenia or low blood counts, bulky disease, and steady disease progression. Right now, there is no evidence that watching and waiting results in a lower Overall Survival than treating right away.
  • Maintenance Rituxan after a treatment does not offer a better Quality of Life than treating and then waiting for a reason to treat.
  • Long-term follow up of patients who received R + Chemo shows that there is no one treatment that prolongs Overall Survival better than others.
  • R-squared (Rituxan + Revlimid/Lenalidomide) continues to impress experts, enough that the results of a phase 3 clinical trial might be enough to recommend that the combination replace chemotherapy as the standard choice.
  • Patients who receive R-CHOP and then have progressive disease within 24 months have a lower survival rate than other patients. This group accounts for about 20% of Follicular Lymphoma patients. One of the big challenges for FL researchers is figuring out how to identify these patients early, and how to treat them.
The second OncLive article features a short video of Dr. Winter, and a lot of the video focuses on that last item -- the 20% of patients who progress within 24 months. It's good that researchers have been able to identify that group of patients, and it's great that lots of energy is going into identifying and treating them early.

So these articles aren't presenting anything brand new. And that makes sense -- they are reporting on a session that was meant to get oncologists up to date on a bunch of things. But it's always interesting to see what FL experts think is important enough to want to make sure all of their peers know about it. I hope we see more in the near future about that 20% of patients.

(And I'm serious about wanting to go to one of these conferences. If any of you is a kindly billionaire who grants wishes, my email is in the profile on the right.)

Friday, October 6, 2017

Obinutuzumab vs Rituxan

The New England Journal of Medicine published an article yesterday on the results of the GALLIUM study that compared Obinutuzumab and Rituxan as part of an initial treatment for Follicular Lymphoma. Obinutuzumab came out ahead.

Or did it?

Obinutuzumab was in the news at the end of August, when it was given priority review by the FDA. The review will also be based on the GALLIUM trial results. Obinutuzumab is similar to Rituxan, in that they are both monoclonal antibodies that target the CD20 protein on B cells. But Obinutuzumab  is considered a possible improvement over Rituxan, because it was created differently, to target B cells better, and to cut down on some of the side effects that come with Rituxan's being made from mouse cells (instead of Obinutuzumab's human cells).

The NEJM actually provides a really helpful video that explains the results of the trial. As shown in the video and the article, the GALLIUM study looked at how effective and how safe Obinutuzumab was when compared to Rituxan in FL patients who had not yet received any treatment. The trial involved 1202 patients. Half of them (601) were given chemotherapy + Obinutuzumab, while the other half was given chemo + Rituxan. The chemo could have been Bendamustine, CHOP, or CVP. Patients who had a Complete Response or Partial Response were then given maintenance treatment for up to 2 years (361 for Obinutuzumab and 341 for Rituxan, or an 88.5% Response Rate for Obinutuzumab and 86.9% for Rituxan).

As you can see, there were slightly more patients who had a Response from Obinutuzumab + chemo than Rituxan + chemo. The study was stopped after almost 3 years when it was clear that Obinutuzumab had a better Progression Free Survival rate for 3 years -- 80%, vs. 73.3% for Rituxan. That number is considered significant enough to say that Obinutuzumab is more effective that Rituxan.

This is one of those stories that's getting lots of play in the oncology community. Rituxan has been around for 20 years, and there have been a bunch of attempts to find something that does the same job, but in a better way. Lots of stories online are suggesting that Obinutuzumab has done that.

But then, there are a few more stories that are looking at a second piece in the NEJM, an editorial called "Which Anti-CD20 Antibody is Better in Follicular Lymphoma?" In it, the authors raise some questions that should be raised, and that should make the "Obinutuzumab is better than Rituxan!" article writers slow down a bit. Not many of them did. Medscape was one -- their article reporting on the research is called "Obinutuzumab vs Rituximab in FL: 'Too Close to Call'."

The Medscape article points out some problems with the study that might make the results a little less simple than it might seem. The PFS is significant -- about 7% better for Obinutuzumab.

But there are some problems, too, as the editorial (and the Medscape article) point out.

For example, there is a dosage difference. Patients who received Obinutuzumab had a dose almost 3 times higher than the Rituxan dose. Those are both standard doses for the two, but it raises the question, if the two treatments are generally the same thing, would a higher dose for Rituxan have given better results?

Also, the Obinutuzumab had a higher incidence of adverse events -- things like low blood cell counts, nerve issues, infections, and infusion-related reactions. All of them were more frequent (for some adverse events, twice as frequent) in Obinutuzumab as in Rituxan. That raises the question -- if there is a higher Progression Free Survival, is it enough to make it worth the higher risk of adverse events?

Finally, the editorial authors point out that, while PFS is higher, there is no Overall Survival benefit. So people might go longer before they need another treatment, but they don't live longer as a result of taking Obinutuzumab instead of Rituxan. (I think, though, that's it's too early to measure that statistic.)

The Medscape article also looks back at the ASH session last year that first reported these results of the GALLIUM trial, that showed problems with Bendamustine and Obinutuzumab (and Bendamustine alone).

The Medscape article ends with some interviews with oncologists about whether or not Obinutuzumab will replace Rituxan. The responses were mixed. I can see why -- the study does raise some questions. And, as one doctor points out, the potential FDA approval will be for this very specific course of treatment -- Obinutuzumab plus chemo, followed by Obinutuzumab maintenance. That might not be the best choice for everyone.

My sense is, human nature being what it is, many doctors will continue to stick with what they know, and that means using Rituxan. And my guess (and it's only a guess) is that it will remain that way until there is a really big improvement in the numbers.

And finally, there is a lesson here for us as patients -- a reminder, really. Online stories about cancer are meant to be read, and that means sometimes making them sound better than they are. Most stories about this study didn't bother with the editorial, and the questions it raised. We need to all be careful (me included) to think carefully about what we see, and to make sure we're getting the full story.

Staying informed is the best way to have a voice in our treatment.

Saturday, September 30, 2017

The Future of Follicular Lymphoma Treatment

About a month ago, I posted a link to a video series from OncLive called "The Evolving Landscape of Therapy for Follicular Lymphoma," which features interviews with two of my favorite Lymphoma Rock Stars -- Dr. Bruce Cheson and Dr. Anas Younes. OncLive does a lot of these video series -- they post a new video every four five days, so the series takes about a month to complete.

It looks like they're getting to the end of this one. It's been a really good series.

The last video is called "The Future of Treatment in Follicular Lymphoma." The good doctors discuss some particular treatments, and how they represent paths that the field might take. Dr. Cheson discusses some kinase inhibitors, for example.

But both doctors also focus on some different issues that are just as important. We would expect them to focus on different treatments and how they work and what we can expect from them. But both doctors also mention a critical part of the future of treatment -- the patient.

Dr. Younes describes the long-term nature of the disease, one that is slow-growing and will probably require multiple treatments over a lifetime. "It's an irritating disease...the anxiety and the inconvenience of coming back and forth for multiple treatments in a lifespan is not ideal."

First of all, I love that he calls Follicular Lymphoma "irritating." I think he's right. It's not that way at first. When we're diagnosed, it's terrifying. But for many of us, as we learn to live with it over time, it becomes....irritating. It's frustrating to not have any symptoms, but to have all the anxiety that comes with waiting for symptoms. I really like that word.

But more important, I love that Dr. Younes recognizes how important Quality of Life is for patients. His solution is a hope that we can eventually have initial treatments that will give us 15 years before we need a second treatment. That's a good, long stretch of time, where maybe we can put this irritating disease out of our heads for a while.

Dr. Cheson also recognizes the need to pay attention to patients' needs. He mentions a new treatment that might be better than one that is currently available, but is less toxic. But is it "better"?  Well, he says, "I think the major issue is the schedule of administration, which is 3 weeks in a row and then a week off. To do this indefinitely, you’re going to have problems with patient compliance."

Very interesting. Sometimes I hear researchers describe Follicular Lymphoma as a "chronic" disease (actually, Dr. Younes uses that word in this video). But if it's "chronic," that means it's going to keep coming back, like, say diabetes. And that means it will need to be treated constantly. And, as Dr. Cheson says, patients are going to have to be willing to keep up the treatment schedule that comes with a chronic disease.

Follicular Lymphoma is different from other cancers. I know all cancers are different, and even FL has a bunch of different sub-types that make the experience really different for all of us. But I really do believe that FL is different on an emotional and Quality of Life level. For a lot of us, we learn to live with this in ways that lots of other cancer patients don't have to deal with.

And so, "the future of treatment" needs to take that into account, as Dr. Younes and Dr. Cheson very helpfully point out.

Whether or not that is actually happening is a different story.

But the important thing is that we patients need to remember that we have a voice, and we need to remember to use it. That might mean being active in working with an individual doctor to come up with a treatment plan that meets our lifestyle goals, and not just one that has a the longest median Overall Survival.

But it also means being active in the lymphoma community when we can, making sure that patients' voices are heard in larger ways, so we have a role in shaping research plans. That's harder, of course, but those opportunities do exist.

Fo now, though, I'm thankful that influential voices like these two Rock Stars are reminding the lymphoma community that patient needs do matter.

Wednesday, September 27, 2017

Managing CAR-T Side Effects

I don't think my friends at the CAR-T and Follicular Non-Hodgkin's Lymphoma blog have gotten to this one yet, but they'll forgive me if I look at it first.

Some folks at MD Anderson, along with colleagues at some other institutions, have published "Chimeric Antigen Receptor T-cell Therapy — Assessment and Management of Toxicities" -- a plan for watching and responding to the potentially fatal side effects that can come with CAR-T therapy.

CAR-T has been in the news in the last few weeks because the FDA approved the treatment for some Leukemia patients. CAR-T thrapy involves removing a patient's T Cells (part of the immune system that attacks invaders) and changing them so they can recognize cancer cells as invaders and take care of them. The results in clinical trials have been excellent -- good enough to justify FDA approval, with more approvals possible in the future (including one, potentially, for some Follicular Lymphoma patients).

The problem with CAR-T is some of the side effects. In a way, CAR-T can work too well.

The potential side effect that causes the biggest problem is Cytokine-Release Syndrome, or CRS. CAR-T has been called a "living cancer treatment," because unlike something like  chemical treatment, T Cells do their job by not just attacking invaders, but by overwhelming them -- when they sense an invader, they signal to other T Cells to attack. So an effective response means a whole army going against the invaders.

Those T Cells are activated by Cytokines, which are proteins whose job is to signal cells. The problem is, the Cytokines signal the T Cells, which then produce more Cytokines. Which signal more T Cells. Which produce more Cytokines.

The body can usually keep this cycle in check, so it doesn't cause too many problems. But sometimes it can't do that. And this results in CRS. The body is overwhelmed by Cytokines and T Cells. At best, it can make the patient feel really horrible (like having the flu, I have read). At worst, it can be fatal, and there has been at least one patient in a CAR-T trial who has died as a result.

Another side effect is neurotoxicity, or toxicity that affects the nervous system. CAR-T treatment can cause a specific type of neurotoxicity called CAR-T-cell-Related Encephalopathy Syndrome, or CRES. This affects the brain in particular.

These very nasty side effects have been dealt with since CAR-T treatments (and other Immunotherapies) have been in trials.

The folks at MD Anderson and their colleagues looked at published studies and about 100 patients to develop a system for identifying CAR-T side effects early, and dealing with them quickly before too much damage occurs. Cytokine release Syndrome does not have to be fatal, but it does have to be treated quickly to keep the worst from happening.

The system involves monitoring the patient for symptoms, grading the symptoms (determining how severe they are), and treating immediately. The treatment could involve "aggressive supportive care, anti-IL-6 therapy, and/or corticosteroids for severe cases." Anti-IL-6 are antibodies that target the Interleukin-6 Cytokine. Corticosteroids are commonly used to stop allergic reactions. Basically, the treatments are used to slow down the immune system response.

Interestingly, one researcher who was not part of this team pointed out that other approaches are also being used in other places, and that the ways to deal with CAR-T side effects are still evolving.

So while there is no guarantee that the system will stop a CRS reaction, but I find it comforting that there is a system being recommended. Lots of very good minds worked together for this, and it sounds like even more good minds will keep working to make it better.

Saturday, September 23, 2017

Taking a Break from Follicular Lymphoma

An anonymous reader posted a comment yesterday on my last post (about Immunotherapies), and I started to respond to it as a comment, but I decided it would be better to put it here, where it might be seen more easily.

The comment said this:

All excellent news! Thank you for keeping us informed! I am approaching my one year diagnosis anniversary, and had a complete response to B&R seven months ago. I'm on the fence about staying informed. On one hand I'd like to put all of this in the rear view. But on the other hand, it's the kind of baggage that keeps hanging on... At any rate, thank you for your efforts! 

First of all, congratulations on the Complete Response! That's awesome, and even more awesome that it is a durable response, and continues to last. I hope it goes on for a long time.

Second, and just as important -- if you need a break, then take it.

This blog is a funny thing (from the perspective of the person who writes it).

I've been doing this for almost 10 years now, and I noticed a distinct pattern a long time ago.

There are people who discover the blog, usually soon after they were diagnosed. And based on what they say in their comments and private emails to me, they spent a few (or more than a few) hours reading the blog, going back a few years, learning new things, and getting into Follicular Lymphoma through my eyes, as someone who lived it. (Some of you might recognize yourselves in there.....)

Very often, those people will continue to read -- eager for every new post. And they'll comment on every one, or send me another email. And I love to hear from them. And then they'll let me know that a treatment worked, and I'll celebrate with them. And then they'll comment some more.

And then, after a while -- 6 months, a year -- the comments and emails will become more infrequent. And then they'll stop, and I'll never hear from them again. Over 10 years, that's happened a whole lot of times.

And I'm fine with that.

The blog is run through Blogger, which is owned by Google. I really like the platform. One of the nice features is its analytics -- the statistics that Google provides to me about readers. Google doesn't tell me anything about individual readers, but I do know things like how many people have visited each day or week, and what countries readers are from (there are a lot -- I've had readers from over 70 different countries in the last year. As I'm writing this, there are people reading the blog from the U.S., Brazil, and France. How cool is that?!).

And I can see patterns in the analytics, too. I will go from a large number of readers, to a slow decline over a few months, so that I have about half as many monthly readers as I once had.

I can put things together. Readership goes up and down, because that mirrors the way Follicular Lymphoma works. People get diagnosed, and they get hungry for information. They get a Complete Response, and they take a break. That's how it works.

And I'm fine with that.

One of the reasons I've never had advertising on the site is that I don't want to be tempted to have a few dollars be the motivation for doing this. If I relied on making money from the blog, I would never say what I'm about to say:

If you need to stop reading, then stop reading. My great hope is that I can give people something that they need. If you don't need it any more -- or if getting it is making you feel worse -- then stop reading.

That makes me a lousy social media manager. But that's not what I am. I'm a patient, like most of you, and I'd want someone to tell me the same thing -- do what you need to do to make yourself happy.

I say it a lot, and I'll say it yet again -- Follicular Lymphoma is an emotional disease as much as it is a physical one. Take a break and heal that part of yourself.

Anonymous reader -- Stop reading if you need to.

When you're ready, come back. I'll still be here.

I promise.

Good luck with the remission. I sincerely hope you never need to be informed about Follicular Lymphoma ever again.

Thursday, September 21, 2017

Immunotherapies for Blood Cancers

The Journal of  Community and Supportive Oncology has a really nice article in their last issue called "Immunotherapies Shape the Treatment Landscape for Hematologic Malignancies."

The journal describes itself as "Research and reviews for the practicing oncologist," so the article itself is a little technical. However, for a not-a-medical-doctor-but-still-a-cancer-nerd like me, it's a fun thing to read.

As the title of the article suggests, the focus is on looking at how Immunotherapies are playing a big role in blood cancer treatment these days. Immunotherapies are treatments that use the body's own immune system to fight off cancer. That's the problem with cancer cells -- they don't belong in the body, but they also have lots of ways of fooling the body into letting them stay. And then they grow  and do bad things.

(They're like your roommate's friend who is going just sleep on the couch for a few days "until he finds something else," and the next thing you know, it's six months later, all of his stuff has taken over the living room, and there's never any milk for your cereal because the "guest" watched The Big Lebowski one night and now he drinks White Russians all day instead of looking for his own place.

That's basically what cancer is. If you don't understand the comparison, just skip to the next paragraph.)

As the article points out, blood cancers are especially good for Immunotherapy, since the immune cells that should be attacking the cancer cells are swimming right beside them in the blood.

The author breaks down some of the Immunotherapies that have been approved or are in clinical trials.

T Cells. The first general way of using Immunotherapy is by "exploiting T cells." T cells are immune cells that work in a bunch of different ways to battle invaders in the body. One common way of using T cells is in Stem Cell Transplants. In an Allo Stem Cell Transplant, someone else's T cells are put into the cancer patient's body. The big danger is Graft Versus Host Disease, where the new T cells attack the patient's healthy cells, thinking they are invaders.

CAR-T. A more sophisticated use of T cells is through CAR-T therapies. They have been getting lots of attention lately, and for good reason. In CAR-T therapies, T cells are removed from the body, changed into something that can recognize cancer cells as the invaders that they are, and attack them. (If you want more news about CAR-T treatments and Follicular Lymphoma, go to the CAR-T and Follicular Non-Hodgkin's Lymphoma blog. They have some nice updates today.)

Monoclonal Antibodies. These are the oldest of the Immunotherapies, and Rituxan is the king. It first appeared in 1997, and it has played a huge role in increasing Survival rates in Follicular Lymphoma. There have been a lot of attempts to create a MAB that is as good as Rituxan, with little success. But that could change. For FL, an Obinutuzumab combination seems a little  better than Rituxan, and some other MABs that target different things are also being tested (like Keytruda, targeting PD-1).

Innovative Design. This group, according to the author, takes Monoclonal Antibodies "to the next level." It includes treatments like "Antibody-Drug Conjugates." Basically, you use a MAB that targets cancer cells, and add a little bit of a chemotherapy (or something like it) so the chemo gets delievered right to the cancer cell. In theory, that should mean the effectiveness of chemo but with the limited side effects that come with a targeted treatment. It also inlcudes BiTEs, or Bi-specific T-cell Engagers. These treatments involve fusing together two antibodies. there are ADCs and BiTEs that are being developed for Follicular Lymphoma, but none are very far along the trial process just yet.

B-Cell Receptors. Finally, there are B-Cell targeting treatments. These aren't really Immunotherapy treatments, but they are kind of hot right now. The target the B-Cell Receptor pathway, the chain of events that keep B-Cells alive and (if they are malignant) doing damage. of course, Follicular Lymphoma is a B-Cell lymphoma, so these treatments are especially important for us. there are some familiar names here, including Ibrutinib and Idelalisib.


So the article provides a nice review of some of the promising developments in blood cancers, including Follicular Lymphoma. Even if you don't read the actual article, click on it and take a look at the charts, just to see how many treatments have been approved recently or are in development. It's impressive.

Of course, not all of them will work for Follicular Lymphoma, but that's OK. It's still hopeful to see how many treatments are in the works -- and this isn't even all of them.

Lots to look forward to.

Monday, September 18, 2017

Another FDA Approval for Follicular Lymphoma: Copanlisib

The big Follicular Lymphoma news from the weekend was the FDA's approval of Copanlisib, also known as Aliqopa, for relapsed FL.

Copanlisib is a type of kinase inhibitor. Like other inhibitors, it doesn't work by directly killing a cancer cell, the way traditional chemotherapy does. Instead, it works by stopping (or inhibiting) a process that keeps the cancer cells alive.

In this case, Copanlisib stops an enzyme that is part of a long chain called the PI3K/AKT/mTOR pathway. In that pathway, a bunch of reactions happen -- an enzyme tells a protein to tell something else that something needs to happen for the cell to grow, or divide, or just stay alive. there are other treatments that target different parts of the pathway, but Copanlisib targets that first part, the PI3K part. Idelalisib is another PI3K kinase inhibitor -- it's a good one to target for Follicular Lymphoma. There are least two other kinase inhibitors being developed for FL.

Copanlisib was given accelerated approval by the FDA, which means it went through the approval process quicker than it normally would. It also means that the approval isn't complete yet. The approval was given based on a phase II clinical trial, that showed good results on a smaller patient population. A phase III trial will need to confirm that Copanlisib is as good as it seems.

The approval is also for a fairly narrow group -- Follicular Lymphoma patients who have relapsed, and who have had at least two prior systemic treatments (a treatment that involves the entire body or "system" -- something like chemotherapy).

The approval points out that many patients who have this kind of treatment history are having a hard time finding something that works, and Copanlisib does seem to work for a lot of them. That phase II trial found that Follicular Lymphoma patients in the study had a 59% Overall Response rate, with a median response of just over a year. Pretty good when you're having trouble finding something that works, and unfortunately, there are a lot of folks in that position.

Of course, there are side effects. Some of them are common in lymphoma treatments -- since they go after immune cells, the side effects involve different types of lowered immunity. But Copanlisib also has some other different side effects, like hyperglycemia, or high blood sugar. Copanlisib effects an enzyme that is involved in insulin production, so the body doesn't process blood sugar as efficiently as it should.

So we have another arrow in the quiver -- another treatment that can be used if the situation is right. That's always good news.

In addition to the phase III trial that will confirm that the approval was justified, there is at least one other trial involving Copanlisib for FL. This one combines it with immunochemotherapy (R-CHOP or R-Bendamustine). Lots of treatments these days seem to work better as a combination with other treatments, so it makes sense that this is being explored.

Lots to look forward to -- potential treatments that could help us all in the future.

(This is a good time to remind you all that treatments can't be studied and approved with people joining clinical trials. So if you are in the unfortunate position of needing treatment, talk to your doctor about clinical trials that might be appropriate -- check here to learn more.)

Friday, September 15, 2017

Happy Lymphoma Awareness Day!

A happy World Lymphoma Awareness Day to you all!

It's an important day for us all. Our special day. Kind of like Mother's Day is for moms, but it's less likely that we're getting breakfast in bed.

It really is an important day, though. I say this a lot when this day rolls around, and it's still true -- it feels strange to set aside a day like this, when I have been aware of lymphoma every day since January 15, 2008.

And if you're reading this blog, my guess is that you are also feeling the same, or something like it. Awareness isn't really an issue for a lot of us.

But Lymphoma Awareness Day isn't just for us. I've been spending a lot of time on various internet support groups and discussion boards devoted to lymphoma, and I'm always amazed at the misinformation people have gotten about lymphoma and other types of cancer.

Part of that is not knowing where to turn. Part of it is, honestly, people looking for shortcuts to getting better, and believing that those shortcuts exist. And for a lot of people, that lack of awareness is from fear -- they either don't want to know because it's easier to just not think about it all, or they fear things like the side effects of chemo, so they look for other ways that they hope will cure them.

Some knowledge would go a long way. there's so much to be hopeful about, so much less to fear than it seems.

OK, my shameless plug -- I talk about some of this in a piece I wrote for The Mighty for Lymphoma Awareness Day. You can read it here. Feel free to share.

Lots of other great resources out there, too, for yourselves and for sharing with others:

And lots more out there. The important thing is, you can do your part -- very easily -- to help raise awareness today, and to do a little extra something to make yourself more aware of your disease. And if you missed The Day, no worries -- it's Lymphoma Awareness Month, too, so you still have plenty of time to spread the word.

Enjoy the day. And if no one served you breakfast in bed today, then have two desserts at dinner. You deserve it.

Monday, September 11, 2017

The Emotional Side Effects of Cancer Treatments

This past week, the European Society for Medical Oncology (ESMO) annual meeting took place. There's some good stuff coming out of it. I know I tend to focus on oncology meetings that take place in the United States, like ASCO and ASH, but I'm becoming more aware of some of these meetings outside the U.S. lately. I plan to look at a couple of Follicular Lymphoma-related presentations over the next week or so.

But first, a report about a session called "Change of patient perceptions of chemotherapy side effects in breast and ovarian cancer patients." I came across this on Facebook, where it was posted by Patients Against Lymphoma, the folks who put together (While I'm here, I might as well link to their Facebook page, too -- consider Liking it if you're on Facebook.) I'm not focusing so much on the breast and ovarian cancer part of this, but on the results that are talked about in the link -- the emotional side of cancer treatments.

I've been focused on this subject a lot lately -- the idea that Follicular Lymphoma is as much an emotional disease as a physical disease, since for so many of us, we watch and wait. Sometimes that watching comes before we even get treatment, and sometimes it comes after we get treatment, even if the treatment was successful. It's kind of the way it goes with an incurable cancer -- we're always waiting for the Big Return that we're told is coming at some point. There's an emotional side effect to all of that, even when there are no physical side effects.

The ESMO presentation was a follow-up to research done 15 years ago. Patients were give chemotherapy for breast or ovarian cancer, and given a survey before, during, and after they had chemo. Patients were presented with two sets of side effects of chemo. One set listed physical side effects, and the other non-physical side effects. they were asked to choose the 5 from each list that concerned them most. then those ten were put together, and they were asked to choose the top five in the combined list.

What the researchers found was that, over time, the concerns change. At the beginning of chemo, there is more emphasis on physical side effects. But as they get used to these, and they get treatment (anti-nausea drugs for example), the non-physical side effects become much more of a concern.

And the researchers noticed. As the lead researcher said, "As doctors, these findings might lead us to consider possible improvements to the accompanying therapies we offer our patients....There is also a clear case for providing stronger psychological support to address patients' social anxieties and family-related concerns."

I like to hear that. I like when doctors recognize the emotional needs of patients, because I think they too often forget about them.

And that matters a lot for Follicular Lymphoma patients in particular. My blood work might be "rock solid," as Dr. R used to say to me. But my anxiety might be spinning like the centrifuge that separated my blood sample -- anything but "rock solid." I'm not so much worried about right now. I might be worried about what happens six months from now, when my daughter starts looking at colleges, and I worry about how I'll pay for it if I get sick. With FL, the worry always seems to be about later.

More from one of the research team members: "The results show that there might be a gap between what doctors think is important or disturbing for patients, and what patients really think. Physical, psychological, social and spiritual support is needed at every stage of the disease....Going forward, similar studies also need to be done for other types of cancer - including analyses of how an optimal management of side effects influences the disease trajectory."

Amen to that. I would welcome and encourage researchers to keep looking into issues like the emotional needs of patients, the ways Quality of Life are affected by treatments, and the unique needs that come with different types of cancer.

In the meantime, you can help yourself by being honest with your doctor and asking for help if you need it. Most hospitals have some kind of emotional assistance programs (a social worker, or psychologist, or some other therapist), so a good oncologist should know about where you can get help.

And there's no shame in needing help. You wouldn't try to tackle the physical problems of having cancer all by yourself (at least I hope you wouldn't), so why would you try to deal with the emotional problems by yourself?

Thursday, September 7, 2017

Vitamin C and Follicular Lymphoma

So while we're on the subject of Vitamins and Lymphoma, let's talk about Vitamin C.

In my last post, I wrote about a recent study involving Vitamin D -- it showed that low Vitamin D levels might result in lower survival rates for Follicular Lymphoma. The researchers admit that more study is needed on this, so don't go swallowing bottles of Vitamin D pills just yet. Talk to your doctor about checking your levels and why it's important.

The journal Cell recently published a heavy research article on Vitamin C called "Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression." When I say "heavy," I mean it has some serious discussion of cell-level processes and genetics. Cell is not a journal about clinical oncology and how doctors treat patients. It's about what goes on in our cells, on the smallest level -- the normal and the abnormal.

So I was happy to get some help with this heavy stuff from an article on Lymphoma News Today, which included some explanation from the researchers in the study.

Apparently, Vitamin C has been an alternative treatment for cancer for a long time -- people think that taking lots of it will stop their cancer. While there is some truth to that (Vitamin C was shown to kill cancer cells in a test tube), research in 2008 on real people showed that giving a large dose of Vitamin C by infusion had few side effects, but also had no effect on cancer. But there was some suggestion that maybe Vitamin C needed some help if it was going to work.

The recent article in Cell helps explain why. Basically, one of the ways that blood cancers form is because of a problem with an enzyme called TET2. When TET2 isn't doing its job, stem cells can't turn into white blood cells. Think of stem cells as baby cells that are supposed to grow up in to different kinds of adult cells. TET2 helps that happen. When TET2 doesn't work, the stem cells don't grow up, but they don't die, either. They go into the blood stream and take up room and cause problems.

So when TET2 isn't working, your body is basically overrun by mutant zombie babies. Let that image sink in for a minute.

Vitamin C seems to help TET2 work again the way it is supposed to by blocking the thing that makes TET2 stop working. No more zombie babies.

But the Vitamin C needs help, too. The researchers found that something called a PARP inhibitor helps the Vitamin C do its job. Inhibitors of different types are becoming more common in all kinds of cancers, including Follicular Lymphoma. The PARP inhibitor stops a protein from fixing DNA in cancer cells, causing them to die. A PARP inhibitor is used now on some kinds of ovarian cancer.

The lymphoma connection here is that there is at least one PARP inhibitor being tested on Follicular Lymphoma.

All of this sounds great. But like the Vitamin D study, there needs to be a lot more research. All of the work done for this article was done on mouse models. there are a lot of steps that need to be completed before this is ever shown to be safe and effective on real FL patients.

So that's the good thing about this study -- we might have an actual treatment strategy come out of it someday (years from now).

In the meantime, while you are avoiding the Vitamin D section at the pharmacy, go ahead and avoid the Vitamin C section, too. At least until you talk to your doctor about whether or not you need Vitamin C for something other than cancer.

Bottom line, as always -- stay informed, talk to your doctor, and if a cancer "cure" sounds too good to be true, it probably is.

Monday, September 4, 2017

Vitamin D and Follicular Lymphoma

The Blood Cancer Journal just published an article "Vitamin D Insufficiency is Associated with an Increased Risk of Early Clinical Failure in Follicular Lymphoma." This isn't the first study on Vitamin D and FL, and it builds on the others in some important ways.

Let's go back a couple of years first. In 2015, the Journal of Clinical Oncology published a study on Vitamin D and FL that said low blood levels of D were associated with lower Overall Survival in patients who had been given Immunochemotherapy (Rituxan or RIT + CHOP). There were lots of alarming headlines in the cancer media about the study, and is the case too often, many of them misrepresented what the study actually said. I wrote about it in the blog -- the study's conclusion said "serum vitamin D might be the first potentially modifiable factor to be associated with FL survival." Might be. It was an interesting study that called for more research before we could know for sure.

The Blood Cancer Journal study gives us some of that research. But let's get this out there right away -- even these researchers say we need more research ("Further investigations are needed to determine whether outcomes could be improved in FL by supplementation with this readily available vitamin.")

I know I haven't even gotten to what's in the research yet, but I think it's really important to make sure, near the beginning of this post, to remind everyone to not jump to conclusions. I've been reading a lot of stuff online lately where people are taking small bits of information about cancer and making them into Big Things that they aren't. This study isn't saying Vitamin D will cure your cancer. I want to be clear about that.

So, about that research.

The researchers looked at 642 Follicular Lymphoma patients who were enrolled in the study between 2002 and 2012. Unlike the earlier JCO study, which looked only at patients who were given R or RIT + CHOP, the patients in this study had a number of different treatments, including R + chemo (CHOP, CVP or Bendamustine), but also straight Rituxan, watch and wait, and other treatments (which they don't list separately). That range of treatments is important, given that there really isn't a standard treatment for FL.

The researchers measured whether low Vitamin D levels had an effect on Overall Survival, Lymphoma-Specific Survival (whether lymphoma was the cause of death), and EFS12, or Event Free Survival at 12 months (this same research team had found that EFS12 was a predictor of Overall Survival -- that is, having FL get worse or come back within 12 months was a sign that Overall Survival was lower than with other patients).

The results (after a median follow-up of just under 5 years) --
For patients given R + chemo, low Vitamin D levels were associated with lower Overall Survival, Lymphoma Specific Survival, and EFS12.
For patients who watched and waited, low Vitamin D levels were associated with lower Overall Survival, but not EFS12. Lymphoma Specific Survival could not be calculated.
For patients given just Rituxan, low Vitamin D levels were NOT associated with lower EFS12, and Overall Survival and  Lymphoma Specific Survival could not be calculated.
When all patients receiving any kind of Rituxan treatment were lumped together, low Vitamin D was associated with all three -- lower OS, LSS, and EFS12.

The researchers are careful to say that more research needs to be done to confirm all of this, though they are especially hopeful that the study can help patients with low EFS12. While different studies have shown that low EFS at 12 or 24 or 30 months can predict low Overall Survival, the challenge is finding a treatment that can help those FL patients with an aggressive form of the disease. Maybe low Vitamin D levels are one way to help?

There are no easy answers here, as the calls for more research demonstrate.

But from my perspective as a patient, I would say that asking your doctor about your Vitamin D levels is probably a good idea. My own doctor (my regular doctor, not my oncologist) had me start to take Vitamin D supplements many years ago, and I continue to take them. She thought D levels were important for lots of reasons (none of them related to Follicular Lymphoma). Did my good D levels help when I took Rituxan? Have they helped me not need treatment since then?

Who knows? Follicular Lymphoma is a funny disease, and it goes down such a strange path that it's hard to know if any of the things we do (aside from actual treatments) have any effect. Follicular Lymphoma is like a toddler on a walk through the woods. It runs ahead sometimes, then stops and looks at bugs, then walks back in the direction it started, then lies down and cries in the grass, then walks ahead again. Same with FL, with its slow progression, waxing and waning, speeding up a little and slowing down again. We really can't know if our diet or exercise routine or supplement regiment is really doing anything for us. We really can't put our hope in something we can buy from a grocery store.

That said, ask your doctor about Vitamin D. It's worth having that conversation.

Friday, September 1, 2017

CAR-T Approval

Some really excellent news yesterday, one of those stories that's all over the internet, and not just getting talked about in the Lymphoma community --

The FDA approved the first CAR-T treatment. This is a big deal. It's a real victory for Immunotherapy -- using the body's own immune system to fight cancer.

Just a quick reminder of what CAR-T is. First, it stands for Chimeric Antigen Receptor T cell therapy. Basically, what happens is T cells are removed from the body. T cells are types of immune cells -- they attack invaders. But not cancer cells, which find ways to make T cells ignore them.

After the T cells are removed, they are changed so they DO recognize cancer cells as bad guys. They are put back into the body, and then the changed T cells attack the cancer cells. The treatment is personalized -- only the patient who had them removed and changed will benefit from having them put back.

(Dana Farber Cancer Institute has a nice article explaining how it works, with a very helpful video.)

The new treatment is called Kymriah, though in clinical trials it was called CTL019 or Tisagenlecleucel. It has been approved for pediatric and adult Acute Lymphoblastic Leukemia, a very aggressive type of blood cancer. Another CAR-T treatment is under review for aggressive lymphomas, including transformed Follicular Lymphoma.

How big a deal is this? I'll let Ben tell you. He runs the blog CAR-T and Follicular Non-Hodgkin's Lymphoma, with help from William -- both are active readers of Lympho Bob, and their blog does an excellent job of keeping up with new developments in the CAR-T world. Ben is a Follicular Lymphoma patient who received CAR-T, and William's wife is also a CAR-T patient with FL. Ben called it "Truly a momentous day in the long and winding history of this life-saving therapy," and he is "Excited to finally see it becoming more widely available to many more patients."

But Ben also points out that there is a high price tag for this treatment -- about $475,000, making it one of the most expensive cancer treatments ever. The company that makes it  has responded to criticism about the price by saying that it is an expensive process -- each patient gets their own personalized treatment. They have also said that any patient who doesn't get a Response within a month will not have to pay for the treatment. (Of course, if the treatment fails on day 45, you're out of luck -- in a couple of ways.)

The treatment has been very effective in trials, but it certainly is not without risks. The biggest of these is cytokine release syndrome, a response from the body to all of those T cells that results in possible fever and brain swelling. One patient in the Lymphoma trial died from this side effect.

Still, the overall news is very positive, and the approval for Kymriah is considered a positive sign for KTE-C19, the Lymphoma CAR-T treatment. It will be interesting to see how many more cancers get a CAR-T treatment, or if the cost will discourage patients and doctors, and thus pharmaceutical companies. But if not, this could be big news for all three.

And I'm always in favor of more options for us as patients.

Monday, August 28, 2017

FDA Priority Review for Obinutuzumab

The FDA announced today that  it will grant Priority Review for Obinutuzumab for patients with untreated Follicular Lymphoma. It's good news.

Let's break this down.

First, "Priority Review" is one of the categories that the FDA (which approved cancer treatments and other things in the United States) developed to try to speed up approvals. A Priority Review is given for a treatment that make provide a significant improvement over what is already available, and it means that a decision will be made within 6 months. For Obinutuzumab (also known as Gazyva), the approval should come before the end of the year.

So what is Obinutuzumab improving on? Why, Our Old Pal Rituxan. They are both Monoclonal Antibodies (which is why "mab" is at the end of the name, like it's at the end of the name Rituxumab and the beginning of Mabthera -- other names for Rituxan).

Like Rituxan, Obinutuzumab targets the CD20 protein on B Lymphocytes (the white blood cells that cause Follicular Lymphoma). What makes it different is that it is humanized (Rituxan was developed from mouse cells) and in theory, that should cut down on some of the allergic reactions that people have to Rituxan (like the one I experienced).

Obinutuzumab is also glycoengineered. That means that sugar molecules are added to them in a way that makes them better at their job (which is to call out to the immune system to attack the cancer cells). The company that makes Obinutuzumab has a cute video that explains it all.

The FDA granted Priority Review based on the results of the GALLIUM trial, which compared Obinutuzumab + chemotherapy with Obinutuzumab maintenance to Rituxan + chemotherapy with Rituxan maintenance. In the trial, after 41 months, the Obinutuzumab patients had a 32% less chance of the disease getting worse.

It will be interesting to see what happens. I think there's a good chance that Obinutuzumab gets approved after the review. (Obinutuzumab is already approved for Follicular Lymphoma as a second line treatment -- for use by people who had taken Rituxan, but had it stop working within 6 months.)

I'm curious what happens after that. Will oncologists start using it in place of Rituxan? There are going to be a bunch of choices in that area soon -- biosimilars might be used in place of Rituxan, too. I have no idea where Obinutuzumab comes in as far as cost goes, and if the cost will make it worth choosing it over Rituxan, even if Obinutuzumab might work slightly better. old habits die hard -- lots of oncologists still go with CHOP, just because that's what they've always done.

As always, it's going to come down to an honest discussion with your doctor.

The important thing, though, is that we might have another choice when it comes to treatment.  And that's good news.

Friday, August 25, 2017

Follicular Lymphoma Videos: The Evolving Landscape for Treatment

We're in that slow period for Follicular Lymphoma news. After the big conferences in June and July, when all of the really interesting research gets shared, everyone seems to go on vacation for the month of August. I'm guessing we will see some more new FL material in a couple of weeks.

In the meantime, though, here are two things to keep you going.

First, OncLive has another video series on Follicular Lymphoma. I've linked to these before -- they post a series of short videos on a topic, putting up a new one every few days, so they form a series when they're all done.

This series is on the topic "The Evolving Landscape of Therapy for Follicular Lymphoma," and it features two of my favorite Lymphoma Rock Stars -- Dr. Bruce Cheson and Dr. Anas Younes. There are four videos in the series so far. I'm guessing there will be a few more.

It starts off with a short video on Diagnosing and Staging FL. At the end, Dr. Cheson mentions the Ann Arbor staging system vs. the Lugano system (named after the conference that takes place every year in Lugano). As he says, the Lugano system is very recent -- from 2016. The Lugano system involves using a PET-CT scan to help with staging. I don't know if it is used "officially" yet, though there are probably lots of people using it.

Other videos in the series (so far) look at Risk Stratifying (figuring out which patients are low, medium, or high risk), and figuring out the best treatments for those risks; and Triggers for Therapies (figuring out when to actually give treatments), something we all worry about, especially those who have watched and waited. There might be some more videos added to the series, so check back there in a few days.

It's all good stuff from two great Lymphoma experts. Not necessarily anything new, but always nice to see something that shows the up-to-date thinking of people in the lymphoma community.


My second item is about the WEGO Health Awards. As I wrote in July, I have been nominated for two awards from WEGO Health -- Best in Show: Blog and Best Kept Secret. A whole bunch of you endorsed me for these awards, and I am so very grateful. The endorsement period ends on September 1, so if you are inclined, please consider endorsing me if you haven't already done so. You can endorse me by clicking here; they will ask for an email address to make sure people don't vote more than once.

After the Endorsement period ends, the three health advocates with the most endorsements in each category will move on to the finals, along with two others who are chosen by a panel of judges. Overall winners will be announced in October.

Thank you all once again for reading. As I've said before, I would write this blog even if no one but my family actually read it (and for a few years, that was true). But it's even better when I have such great readers who don't feel obligated to send me birthday cards and make conversation with me at Thanksgving dinner.