Please Take This Survey about Follicular Lymphoma

Hello all.

I'm finally putting up that post that I promised last time. 

I'm linking to a survey here, and I'm asking you to please consider taking it. The link comes directly from the Follicular Lymphoma Foundation, so it is safe.

https://hab.medefield.com/wix/01234/p979123129511.aspx

The FLF developed this survey (I helped a little bit!) to better understand how patients with Follicular Lymphoma make decisions about treatments. It can also be taken by caregivers and physicians to get their input as well. (The survey will direct you to a different version after it asks you if you are a patient, a caregiver, or a physician.)

The survey is open to residents of the United States, United Kingdom, Canada, Australia, and Spain. You can see the survey in English or Spanish. The announcement for the survey is available on the FLF website if you'd like to read a little more about it.

The survey should take about 10 minutes to finish (maybe 15 minutes if you read slowly and carefully like I do). It is completely anonymous.

The survey will first ask you some basic information, and then it will describe the survey methods for a few screens to make sure you fully understand what you need to do. I don't want to give too much detail here, but it will basically ask you to choose between two hypothetical treatments (they aren't real, or even in development). They will distinguish between the two treatments by showing how type are different, in terms of how long you are likely to be in remission, what kinds of side effects are common, and how it is administered. You'll choose the treatment that you would prefer. You'll do that 11 times. 

It's not hard at all, once you read through the descriptions of how it all works. 

The FLF plans to present this information at a future medical conference. They hope the information will be seen by researchers and influence how they develop new treatments. (For example, if the survey showed that patients with FL would overwhelming prefer one way of administering treatments, then maybe researchers will be sure to develop treatments that can be administered that way.)

So this is your way to potentially have a hand in how research gets done in the future. Very cool. 

 

Thanks for taking the survey. It helps all of us.

 

National Workshop: Lymphoma Research Foundation

Well, I have a post that's all written, that I had planned to put up this weekend, but I need to hold off on showing it to you. I'll explain later.

For now, here's a reminder that the Lymphoma Research Foundation is holding its virtual National Lymphoma Workshop on November 16. This is a day-long event, completely online, and it's all about the latest research in Lymphoma ("Understanding Lymphoma Basics and Current Treatment Options").

The workshop is chaired by Dr. Neha Mehta-Shah of Washington University in St. Louis, Dr. Craig Portell of the University of Virginia, and Dr. Carrie Thompson of the Mayo Clinic. I'm not as familiar with the work that Drs. Mehta-Sha and Portell do, but I've written before about Dr. Thompson, who does  a lot of research on Surviorship and Quality of Life. I think she's great. I'm sure the other two will be equally good. 

I attended one of these in the past, and it was excellent. You can expect to hear information that it meant for patients who are newly diagnosed,  those who are relapsed/refractory, and information about survivorship. There will also be a session devoted to Follicular Lymphoma, where they may talk about treatment options, clinical trials, and new therapies. And there will be a chance to submit questions for the experts to answer.

Registration is required. You can find out more details and get the registration link here.

I'll have more for you soon. This is about my busiest time of the year for me, with lots of work stuff, plus some really interesting cancer-related advocacy work that I'm doing. I'll try to share more about it when I can stop and take a breath.

Stay well.

Watching and Waiting and Wondering

There was a comment on a post from earlier this month from an anonymous reader that made a good point -- lots of what we read is based on what has happened to a group of people, but there is a lot of variation within that group. So much of what happens to patients with cancer is very personal, in the sense that each of our situations is very different from other patients'. I think that's especially true of patients with Follicular Lymphoma, since our disease is so variable. People with the same diagnosis (grade 2, stage 4, whatever) can have incredibly different experiences. It's good to remember that.

The anonymous reader who left the comment followed up with an email, and we had a very nice exchange over a couple of days. (I'm always happy to get emails and comments  from readers.) His name is Joel and he's fairly recently diagnosed. He shared his story, and some of the details were very familiar. Joel was diagnosed at 40 (same as me). Grade 1, Stage 3 (me too!). Very active and healthy (I was running 5k and 10k races at the time). Diagnosis was kind of accidental (I was getting over pneumonia and a large node showed up on a chest scan, and then another node popped up near my hip). Very similar stories!

I hope the similarities continue. I feel like I've had a very lucky path as a patient with FL. The disease has remained fairly slow-growing for me and hasn't caused me too many problems. I know that's  not true for everyone.

One of the other things we talked about was making treatment decisions, especially for that first treatment. As you might know, if you've been reading for a while, my FL was slow-growing enough at first that I was able to watch and wait for two full years before I needed treatment. And then I had six rounds of Rituxan. I haven't needed treatment since then -- almost 15 years. 

Like I said, I know how lucky I am.

At about the same time we were having this exchange, I got an alert about a new article from WebMD called "Follicular Lymphoma: Why “Watch and Wait” May Be the Best Approach." A better title might have added "for some patients." It's obviously not true for all patients with FL, which the full article makes clear. And that's the point of all of this -- we all have different situations, even of they seem similar on the surface.

I made a video a few years ago that introduced a WebMD slide show on what patients should do their own careful research. It is, sadly, no longer online. WebMD can kind of a mixed bag. They can be incomplete and alarmist sometimes, and really useful at other times. I think this article on watching and waiting is actually pretty good. It explains the idea well, and gives what I think is solid advice on whether or not it is appropriate, and when it is time to switch from waiting to treating. I remember seeing an article on watching and waiting right after I was diagnosed, when I was first doing internet research and trying to figure out what FL was. I remember seeing the article and thinking "Who the heck would get a cancer diagnosis and not have treatment?" A month later, that was me. It says something about how poorly that article was written. I think the WebMD article would give good advice to someone who was trying to make that decision. 

It's rare that someone who has just been diagnosed has a clear enough head to be able to do that kind of research and make an informed decision. (Joel is a full-on Cancer Nerd, based on our exchange. I can confirm.) Much easier to see clearly when the initial shock of a diagnosis has work off. That's one advantage of being diagnosed with a slow-growing cancer like FL -- for many of us, we have some time to learn and then make decisions. 

And after we've had active treatment, we hopefully have time to continue learning and being prepared for any future decisions (if that's how we choose to deal with it -- pushing it out of our heads completely is also an acceptable choice).

All of this has been going through my head for the last few days, since Joel first wrote. Getting a new diagnosis is so hard. I am grateful that I found an online support group for NHL with some people who were willing to share their stories and give some information. I grew pretty close to some of them, and I still keep up with their lives. It's so important to share what we know. And it doesn't have to be all Cancer Nerd-y stuff, either. Just our living through what we have lived through is worthy of sharing, and incredibly valuable to other patients. If nothing else, it gives them hope. They know there's a tomorrow. Sometimes that doesn't seem like a sure thing, especially when you've just been diagnosed.

So I hope Joel, and any other folks who were recently diagnosed, are doing well and finding the knowledge and support and comfort that you need. 

Take care, everyone.

Pembrolizumab (Keytruda) for Follicular Lymphoma

The medical journal eJHaem just published an article called "A Phase 2 Study of Frontline Pembrolizumab in Follicular Lymphoma." It's very interesting to me for several reasons, most importantly because it reports the results of a clinical trial for Follicular Lymphoma. But there are others, too, which i will get to.

Pembrolizumab is also known as Keytruda, and it is a very important treatment in cancer. It is a PD-1 inhibitor, meaning it stops the effects of PD-1, or Programmed Death 1. It's a very cool immunotherapy treatment. PD-1 is a protein that is an important part of the immune system, because it keeps immune cells from doing their job too well. If an infection occurs, PD-1 keeps the immune system from attacking too many cells, which would result in an autoimmune issue, where the immune system attacks healthy cells. It send s a"programmed death" signal to some immune cells, basically telling them to stop working. 

In terms of cancer, PD-1 works on immune cells that could be going after cancer cells. So a PD-1 inhibitor stops the PD-1 from stopping the immune cells. In other words, it allows the immune system to work on the cancer cells. 

What makes Pembrolizumab so important is that it works on lots of different cancer cells. We usually think of cancer in terms of body parts -- breast cancer, colon cancer, blood cancer. When we think that way, it makes us think of the cancers as all being very different. A traditional chemotherapy that works on breast cancer probably won't work on lung or brain cancer. 

But the discovery of PD-1 changed all of that. PD-1 is present in the cells of lots of different body parts. So Pembrolizumab has been approved for use in patients with lots of different types of cancer -- melanoma, several lung cancers, classical Hodgkin's Lymphoma, urothelial carcinoma, head and neck cancer, and renal cell cancer. Former U.S. President Jimmy Carter received Pembrolizumab; he might be its most famous user.It's been a real game-changer for many patients with many types of cancer.

But not Follicular Lymphoma. 

I've written about Pembrolizumab and FL a few times. The first time was in 2016. I looked at a couple of pieces that Dr. John Leonard had written about new treatments for FL, and he mentioned a phase 2 study of Pembrolizumab and Rituxan. In the other times I've mentioned it, it was usually to say that results from a study weren't as strong as researchers had hoped. 

And that's the case with this one, too. It look at a phase 2 study of just Pembrolizumab indolent B cell lymphoma, including FL. In this fairly small study, 9 patients with Follicualr Lymphoma were enrolled. The Pembrolizumab wasn't very effective -- 3 of the patients had a partial response, 3 had stable disease, and the other 3 had their FL get worse. Safety wasn't much better than effectiveness. Two of the patients had grade 3 (serious) side effects. Both had transaminitis (high levels of liver enzymes and the blood) and one of them also had hypophysitis (an inflamed pituitary gland).

All of that was enough for the researchers to say "Frontline pembrolizumab for FL is associated with limited responses and a clinically significant rate of IRAEs. Alternative strategies for targeting the TME [Tumor Microenvironment] in FL should be explored." in other words, this one isn't working.

It certainly makes sense to give Pembrolizumab a try in FL. Why not? It works in lots of other cancers, even in another blood cancer (Hodgkin's Lymphoma). But for whatever reason, inhibiting PD-1, at least with this treatment, just doesn't do the job. 

As I said, the results are most interesting to me, but there are some other things about the article that are also interesting.

First, I love the title -- "A Phase 2 Study of Frontline Pembrolizumab in Follicular Lymphoma." If this had been a successful trial, the results would have been given to us upfront, something like "Pembrolizumab Induces Durable Response in Follicular Lymphoma: Results of a Phase 2 Study."I learned that lesson long ago. When you're writing an email with good news, put the good news in the subject line. If it's bad news, make the subject line neutral and bury the bad news in the middle of a paragraph halfway through the email. It's fascinating that the same strategy turns up here.

But even more fascinating is that the bad news turns up at all. It is very rare to see a negative study get published. I could find dozens of examples in this blog over 16 years of reports of phase 1 and phase 2 studies that were very enthusiastic, but were never heard from again. The later studies weren't successful, the researchers never reported the results. I would love to see more negative studies published. They can be just as helpful as the successful ones.

But those studies were also probably commercial, and if a business has sent millions of dollars trying to develop a treatment, they really have no incentive to advertise to the world that the treatment didn't work out. More likely, the company died and the people working for it moved on to something else.

What makes this study different is that Pembrolizumab was already a successful treatment, already making billions for its makers. The authors aren't business people; they are academics and researchers, doing a study with a treatment that has already been approved. They really do have some incentive to share what they learned, even if the treatment wasn't successful. The study was successful -- we learned something from it.

So I'm enjoying this "failure," because it is so rare to read one. I don't think we've seen the last of Pembrolizumab for Follicular Lymphoma. There are still some studies out there. Maybe one of them has just the right combination or the right dosage to make it work. It would be great to add FL to that long list of cancers that Pembrolizumab can treat successfully.

But in the meantime, as the authors of the article say, it's time to try something new and stay hopeful.

FLF Patient Survey Results

The Follicular Lymphoma Foundation published the results of its recent survey of Follicular Lymphoma patients. The survey focused on immunotherapy and communication preferences. There are some really interesting results, even for someone like me who spends a lot of time thinking about FL.

The FLF, for those who don't know, is an organization with a global mission. They provide information and support for FL patients, including funding some important research. If you haven't been to their website, it's worth a visit.

Their global mission is reflected in the survey. They include results from 791 FL patients from 49 different countries. 

One question that they asked was which treatments the patients had received. Almost 60% had received some kind of chemotherapy. 18.2% had Rituxan or Obinutuzumab on their own. 6.2% had R-squared. And 19.5% had received some other treatment. That's always interesting to me, as someone who reads (and writes) about new treatments a lot. It's easy to think that traditional chemo must be on its way out. But even with newer possibilities, chemo remains not just one options, but the option for many patients. And of course, it's a very effective option for many patients.

Along those same lines, only 1.6% have received CAR-T and 2.9% have received bispecific antibodies. Those are very small percentages, given how much excitement there is around them.

Part of the issue is they are approved for a very small percentage of patients. And then there is the cost associated with something like CAR-T.

But this is all a very good reminder for myself that what I write about is often the future, and not the present. All of the excitement, all of the clinical trials, all of the research -- that might be the reality for us in the future. But right now, patients are much more likely to get chemo, or Rituxan, or even R-squared. They are the "standard of care." It's definitely worth understanding what kinds of treatments are out there, because not every oncologist will go to the newer stuff.

Along those lines, another interesting result from the survey -- respondents were asked to rate their awareness of immunotherapy from 1 to 5. The average was 2.16. The FLF says this result was pretty consistent no matter what country they came from. That's very low. There's a critical need for information among FL patients.

When asked which types of sources they found most helpful, or would like to see more of, the respondents said Educational videos featuring healthcare professionals were most helpful. (The FLF has a bunch of these on their website.) Next came testimonials or surveys from other patients, then scientific articles, and then Frequently Asked Questions from other patients. None of these really surprise me, and it's good to see that healthcare professionals are most helpful. Patient stories are great, and I love reading them. But I've also seen lots of less-than-helpful information from other patients. It's good to see FL patients are valuing good information.

That said, the FLF would also love to hear patient stories as well. If you're interested in sharing yours, read more here about how to do it. 

There are lots of other interesting results from the survey, but I want to highlight one more. Just 9% of FL patients in the survey said they have participated in a clinical trial. They seemed really low to me. So I looked at an article from the Journal of Clinical Oncology from earlier in this year that looked at how many cancer patients in the United States have participated in a clinical trial. 

That article said that just 7% of cancer patients in the U.S. have participated in a clinical trial for a treatment. So the FL population seems more or less in line with that. But that article pointed out that clinical trials are only one kind of research that cancer patients can participate in. Almost 13% have been involved in biorepository research (where a tissue sample is saved for later examination), 7.3% in registry research (where their medical records are used for studies), 3.6% in genetic research, 2.8% in Quality of Life research, and  2.4% in economic research. So while we should all at least consider clinical trials for treatments when appropriate, we should also remember that there are lots of other ways to help with research.

So the Follicular Lymphoma Foundation survey is pretty interesting, and I encourage you to read the article that discusses the results. And while you're there, take a look around the rest of their website. Lots of god stuff there,

Humor and Cancer

About a month ago, I came across an article in the Journal of Clinical Oncology that I thought was interesting, and I forgot about it until this morning. It's from a special section of the journal called "The Art of Oncology," where they publish personal stories from doctors and other healthcare professionals (and occasionally patients). The rest of the journal mostly deals with the science of oncology, with heavy research. But the art of oncology is about other things, mostly dealing with people. That part is a lot messier than the science.

The article I looked at was called "Just Humor Me," and it's by an oncologist who argues that the cancer clinic is an appropriate place for laughter. (If you are sometimes hesitant to read the things I link to because they can be hard to read, then try this one. Very readable.)

I would certainly agree that the cancer clinic is a place for laughter. But I think pretty much every place is a place for laughter. I'm not the only one. The author shares some research: "One survey of patients undergoing radiotherapy in Ottawa found that a stunning 86% of patients felt that laughter was somewhat or very important to their care, whereas 79% felt that humor decreased their level of anxiety about their diagnosis. If we had a drug that decreased anxiety levels in 79% of patients, had minimal to no side effects when used correctly, and cost the health care system zero dollars, should not we be using it?"

That's a very good point.

I used to write a lot more about cancer humor (search for "cancer humor" in this blog and you'll see some of those early posts). I think I do less of it now because humor is still important to me, but it's maybe less vital to my health. When I was first diagnosed, humor was definitely a coping mechanism, which is common for many patients (or Follicular Lymphoma or any other disease or condition). There was definitely a sense for me of "not letting cancer win" by taking away something I love -- laughter. 

I remember, a few days after getting diagnosed, my parents came to visit, so they could see how we were doing and try to gauge how out young kids were doing. My parents were in the other room playing with their grandchildren, so I finished making dinner and set the table. My mom heard me banging around the kitchen, and came to see if she could help. Too late; I had already gotten everything ready. So I said, "I did it all. Nice. Make the guy with effing cancer do all the work." She laughed, which was what I expected. Then she hugged me and said, "WE shouldn't be laughing at this." To which I said, "We can't ever stop laughing at this."

A few years later, after she was diagnosed with ovarian cancer, we all went to a baseball game. She and got in line to get ice cream for everyone. As we got to the front of the line, I whispered to her, "You should tell the ice cream guy you have cancer. Maybe he'll give it to you for free." She laughed. "I can't do that." But after she ordered, she said very quietly, "I have cancer." The young man didn't hear her, or didn't know what to say, and as we walked away, Mom said, "I didn't even get free sprinkles." It made me laugh. 

I laugh, too, at the absurdity of it all. I went to the dermatologist a couple of weeks ago to follow up on my skin cancer surgery from about a year ago, and as I got undressed, the nurse turned her back on me. Which was polite and appropriate. But all I could think of was, "Why bother, nurse? Do you know how many people have seen me without my clothes on in the last 16 years? Doctors, nurses, residents, technicians, probably a few janitors. The idea that it would embarrass me is absurd." I didn't say that out loud, but I thought it. The sheer ridiculousness that I got diagnosed with cancer at age 40 when I was in the best shape of my life is worth laughing it. 

I guess I write less about cancer humor these days, too, because I have a better sense of who is reading the blog. I know laughter comes to people who are open to laughter. Especially when a diagnosis is new and raw, or when things aren't going as hoped, it's hard to laugh. You have to be open to laughter before you can laugh.

I remember a few years ago, my wife and I were talking on the phone, and a friend of ours walked up to my wife to say hello just as my wife let out a big laugh. "Who are you talking to? our friend asked, and my wife said it was me. "Oh my gosh," our friend said. "I thought for sure you were having an affair and talking to your new man." She couldn't believe that y wife and I still made each laugh after being married for so long. I think about that a lot. We've been married for almost 32 years. If we stop laughing with each other, that's when I would know our marriage is in trouble. You have to be open to laughter before you can laugh. Sometimes that's just not possible for someone with cancer (but it's my wish for all of us).

So I hope you find something that makes you laugh every day, even if it isn't humor that is directly about cancer. But if you can find the humor in that, I think you're doing alright.

Have a happy day.

How Useful Are GELF Criteria?

The journal Haematologica just published a very interesting study about GELF criteria in Follicular Lymphoma. In some ways, it's a very Cancer Nerd kind of thing, but it also has serious implications for all of us as patients.

The article is called "Impact and Utility of Follicular Lymphoma GELF Criteria in Routine Care: An Australasian Lymphoma Alliance Study." It looks at 300 FL patients in a database and examines their GELF criteria, treatment decisions, and outcomes.

At this point, you are probably wondering what GELF criteria are and why they matter. GELF stands for Groupe d'Etudes des Lymphomes Folliculaires (Follicular Lymphoma Study Group), a French organization that developed a set of criteria to help determine when a Follicular Lymphoma patient needs to be treated. Because FL is slow-growing, and many of us don't need treatment immediately, the GELF criteria help to make that decision. 

The GELF criteria are:

• Any tumor mass greater than 7 cm (about 2.75 inches)
• Involvement of 3 or more nodal sites, each at least 3 cm
• B symptoms (night sweats, weight loss, etc)
• Enlargement of the spleen
• Compression syndrome (swelling that decreases blood flow)
• Pleural or Peritoneal effusion (fluid build up in lining of chest or abdomen)
• Leukemic phase (cancer cells in the blood) or cytopenias (low blood cell levels).

Having any of these issues, according to GELF criteria, means the patient has "high tumor burden" and should begin treatment immediately. To be clear, I'm not giving full information here. Go to this site and you can see more, like the exact blood cell levels that count as cytopenias.

And my giving less-than-full information is kind of part of the problem. More on that later. 

According to the article, one of the problems with GELF are how they are used. If you look at clinical trial criteria, many of them restrict enrollment to patients with high tumor burden -- meeting at least one of the GELF criteria. This is done to ensure that there is at least some kind of consistency among the patients in the trial.

The problem, though, comes when GELF is applied to real-world situations. Or not applied. 

In their analysis, they found, for example, that about 54% of patients in the study (163 of 300) were "high tumor burden," meeting one or more of the criteria. However, about 10% of those high tumor burden patients (16 of the 163) did not have treatment immediately, as the criteria would suggest, and instead watched and waited. And of the 215 patients in the study who did have treatment right away, 34% (74 of the 215) met no GELF criteria, meaning they did not have high tumor burden and may not have needed treatment right away. 

Clearly, GELF criteria are not necessarily being used by all oncologists to decide when a patient needs to start treatment. 

What's more, the study looked at outcomes, and found that, for both patients who watched and waited and for those who started treatment right away, the GELF criteria did not predict Progression Free Survival. In other words, meeting one or more criteria did not predict whether or not treatment would keep the disease in check.

The authors call for more research to try to figure out this disconnect. It's important for all of us. If clinical trials are being restricted to certain patients, there is an assumption that those patients will benefit from a treatment that gets approved. But if, in the real world, that same restriction isn't being applied to patients who receive the treatment, then that might ultimately be a waste. If patients with high tumor burden are determined to not need treatment right away, then those receiving treatment based on GELF criteria might be being treated unnecessarily.

There's another issue worth mentioning that's important to patients. I think we often see something like GELF criteria (or something like FLIPI) when we are researching our disease, and we misunderstand it. I think this happens early on, especially, soon after we are diagnosed. There are some good sites that describe GELF, like the one I link above and again here.  But there are lots of other that don't give very good descriptions. And frankly, the article I'm discussing is one of them, which gives an abbreviated list of GELF criteria without all of the important detail ("Patients required one or more of the following characteristics to be considered ‘high’ tumor burden according to GELF: any tumor mass >7 cm diameter; ≥3 nodal sites (each >3 cm diameter); B symptoms; splenomegaly; compression syndrome; serous effusion; leukemic phase or any peripheral blood cytopenias"). 

It's easy for a patient to read something like that and panic, thinking they need treatment immediately. The research in the article suggests otherwise, and that's why I tried to highlight that my own list above is not as detailed as it could be. These kinds of official lists, which try to quantify something that is hard to put a number on, make everything seem really definite. Numbers are tricky things, and they don't always represent the certainty that they seem to. A GELF number doesn't always signal a need for treatment, like a Overall Survival figure doesn't say anything about our own individual situations. Follicular Lymphoma is too heterogeneous a disease to have numbers provide any kind of certainty. It's just to different for each individual patient.

So if you're a Cancer Nerd and you enjoy diving into the analysis of statistics and outcomes, I hope you enjoy the article. But even if you're just a non-nerdy FL patient, this is all a good reminder to be careful with what you read and don't jump to conclusions about how the statistics for a large number of patients might affect you as an individual. If you read something and panic, do your best to take a step back, take a deep breath, and make a note to talk to your oncologist about it. We're all different.

Have a great day, and thanks for reading.