Treatment Options for R/R Follicular Lymphoma (video series)

The ASCO Post, a kind of newspaper for oncologists, published a video series on treating relapsed/refractory Follicular Lymphoma. If you've been reading for a while, you know how much I enjoy watching video series like this one. I like listening to experts get excited about treatment options. 

For this series, the participants are Dr. Andrew M. Evens (Rutgers University), Dr. L. Elizabeth Budde (City of Hope Medical Center), and Dr. Carla Casulo (University of Rochester). What's especially interesting about this series is that instead of talking about treatments in general, they look at case studies of specific patients. That matters -- with a disease that can look really different for different people, it's interesting to see the kinds of factors that the oncologists consider when making treatment decisions. Of course, seeing the actual patient would be even better -- knowing their goals, their families, their histories, all of the things that make them people and not just "case studies." But even the few specific clinical details that are given are better in some ways than looking at statistics from a group of 100 patients in a clinical trial.

(By the way, each of the videos includes a transcript, in case you'd rather read or need to translate.)

The first video focuses on a patient who was diagnosed with grade 1/2 Follicular Lymphoma, and had successful treatment with Bendamustine and Rituxan. But the FL returned just 8 months later, making the patient POD24 (Progression of Disease within 24 months after receiving immuno-chemotherapy). About 20% of FL patients are POD24, and POD24 patients have a statistically lower survival rate than most FL patients. Reseachers have been payin special attention to this group, trying to identify biomarkers that could signal POD24 early on (right now, there's no clear way to predict it -- you just have to wait for it to happen).  The discussion in the video talks about what POD24 is, the types of treatments available, and whether Auto Stem cell Transplants (using the patient's own stem cells, not a donor's) is still happening these days (you don't hear much about SCT anymore).

The second video discusses a patient who had successful treatment with Rituxan, followed by Rituxan maintenance. This worked for about 4 years, but then he had some leg swelling that showed a return of the FL. More importantly, he had multiple comorbidities -- other serious health issues -- that needed to be taken into account when deciding on a second-line treatment. The conversation for this video focuses on the importance of biopsies and molecular testing to determine a stage and grade for FL that has returned, and how those comorbidities influence the treatment recommendation. (I'll let you guess which treatment they recommended, then watch the video and see if you are right. I was sort of right.)

Finally, the third video looks at a patient looks at a patient who was treated with R-CHOP (a chemotherapy), and then with B-R when he relapsed (a second chemotherapy), and then presented again with grade 3 FL. This is yet another different situation, as the patient is in a high risk category and has exhausted his chemo options. If you guessed that this third-line treatment decision comes down to choosing between CAR-T and bispecifics, then give yourself a gold star for paying attention to what's going on in the world of FL.

As I said, it's an interesting series, and the focus on actual individuals really emphasizes how different this disease can be. It highlights how important it is to have conversations with your oncologist. I'll speak for myself -- I consider myself lucky to not need treatment right now, and that has given me time to stay up on what my options are. Maybe more importantly, it's given me time to let my oncologist get to know me. When the time does come for additional treatment, it won't be a case of just looking at numbers. He'll have a sense (I hope) of what matters to me, what my treatment goals are, and who I am. I think that's important.

I hope you enjoy the series.

Is Accelerated Approval Successful?

 I know that title is a little click-baity, but I couldn't come up with something short that really captured the complexity of this issue.

The Journal of the American Medical Association published a study last week that looked at treatments that were given Accelerated Approval in the last 10 years. It's called "Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval." The question they sought to answer (and this is quoted from the article) was "What is the clinical benefit of cancer drugs granted accelerated approval, and on what basis are they converted to regular approval?" In other words, how successful are cancer drugs that are given accelerated approval?

A little background, just so we're clear on what all of this means and why its important. The issue has been on my mind a lot lately, as a couple of posts that I wrote last month would indicate.

Most treatments that get approval from the FDA use the results of a phase 3 clinical trial to provide data for the application. Phase 1 trials are usually very small, and their main purpose is to show safety -- they help determine the best dose of the treatment to be effective while being safe. Phase 2 trials focus more on effectiveness, and use a larger number of patients to show that the treatment actually works. Phase 3 trials are, ideally, randomized and double-blind, meaning the new treatment is given to half of the patients in the trial, while the other half gets the old treatment (the "standard of care" -- the one that patients would usually receive). This allows for a direct comparison between the new and the old, so the FDA can see that the new is more effective and/or safer than the old. 

With accelerated approval, the makers of a treatment can apply to have their treatment approved after the phase 2 trial. Accelerated approval is usually given for treatment classes that are brand new, allowing a potentially life-saving treatment to get to patients faster then if they went through the full trial process. This benefits patients because a treatment might get to them sooner. And it certainly benefits the maker of the treatment because they can start making money (and recouping the money they put into research) sooner. 

But part of the deal is that the clinical trial process has to continue. A "confirmatory trial" has to happen to show that the good results from the smaller phase 2 trial will actually hold up over time. If the trial is successful, then the treatment gets full approval. If not, then the treatment is withdrawn.

The JAMA article, then, wants to know just how successful those accelerated approvals are -- how many actually go on to get full approval.

The authors looked back at the 129 cancer treatments that were given accelerated approval by the FDA between 2013 and 2017, and then looked at the 46 of them that had follow-up data after 5 years. The results were not great, in terms of how many showed an improvement in survival or quality of life -- only 20 of the 46 (or 43%).

Despite that, 29 of the 46 (63%) went on to get full approval. Another 10 (22%) were withdrawn, and 7 of the (15%) were still in the confirmatory trial process.

Looking at those 29 that did get full approval, only 7 of them (24%) were shown to improve both overall survival and quality of life. Another 7 improved overall survival but not quality of life, and 6 improved quality of life but not overall survival. The remaining 9 did not improve either one.

Those number are very important, which is why I'm sharing them, but I also have to point out some limitations here. I'm not able to access the full article, so I'm not sure how they measuring "quality of life." Overall survival is easy enough to measure, but quality of life is harder, and I'm not sure every study uses the kinds of patient-reported quality of life measurements that I'm familiar with. I guess that's how they measure safety, looking at the side effects that patients experienced? That would be the standard measurement in a clinical trial. If that;s the case, I really do not like referring to it as "quality of life." That completely ignores a whole lot of things that should be included in a measurement of the quality of life. 

Aside from that, Overall Survival is a complicated measurement, too. There are certainly cancers that are so aggressive that new treatments are successful when they add months to a patient's life. Then there are others, like Follicular Lymphoma, that have OS measured in years. The measurement can be so long that the median OS hasn't been reached in 5 years. That's actually very common in FL treatment trials, which is why they use Progression Free Survival as a measurement instead. So without looking at the full article, I can't tell if they are counting something like that as improving OS or not improving OS.

This is what I meant when I said it was all kind of complex.

Ultimately, though, I'm not sure those details matter.

The authors of the study provide this conclusion: "Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval. Patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes."

I would hope that any conversation about treatment with an oncologist would include that information, and that any oncologist would take that into consideration before recommending it to a patient. But I also know, based on the kind of enthusiasm that lots of oncologists had for PI3K inhibitors, that they aren't going to wait for full approval before using them, and that even a preliminary OK from the FDA is good enough. And probably should be.

So, I'll ask the question again that I ask in my title -- Is Accelerated Approval Successful? 

By some measures, No, it isn't. If more than half of accelerated approvals don't result in a better experience for patients, then it seems like the system failed. On the other hand, if the goal is to get new improvements to patients more quickly, than it's a success. And if a large number don't get full approval, then that IS a success. Arguably, the system works -- the treatments that aren't doing the job don't last. If the FDA gave them early approval and then just forgot about them, that would be a problem. But the follow-up makes sure that they are as god as the smaller trial showed.

Of course, "success" isn't just about how well the system works. It's about the patients who get the treatments. Every confirmatory trial that failed means a bunch of patients who didn't get the treatment they had hoped for. And that hurts to think about. From what I can tell, a lot of the treatments get accelerated approval because they offer something that available, standard-of-care treatments can't offer. Think about something like a bi-specific. It works on cancer cells in ways that no other treatment works. If the confirmatory trial involves mostly patients who have tried everything else they could, and they have hope for this new thing that might work in a different way, then that's a success. Clinical trials are necessary, and trials need participants. 

It's all so complex. 

In the end, I think Accelerated Approval has its place, and the authors are right -- being fully informed is key to it all. Talk to your oncologist about treatments, about clinical trials, and about anything else that concerns you. (But you knew that already, you smart, informed FL patients....)

Great Debates: Alternatives to CAR-T

There's a really interesting speaker series that happens every year in New York City called "Great Debates and Updates in Hematological Malignancies." Basically, a bunch of famous oncologists get together, two of them pick sides of a debate about blood cancer, each one speaks for a while, some others comment on what they said, and they move on to the next debate.

It's probably a little bit misleading to call them "debates." I'm not sure they really expect there to be winners and losers. It's more like they are exploring together, looking at issues that don't have definite answers, and offering there thoughts. It's really an alternative format for the kinds of "update videos" that I like to post every now and then.

Follicular Lymphoma seems like a natural fit for something like this, since there really aren't any clear answers when it comes to our disease. Usually at ASH or ASCO every year, someone makes a presentation that looks at the last 10 years or so of FL diagnoses in a database, and how the patients were treated. And the treatment choices will be all over the place -- some watch and wait, some Rituxan, some traditional chemo (some of them Bendamustine and some R-CHOP), some R-squared, plus a bunch of treatments in clinical trials. You see what I'm getting at, I'm sure. There is still no clear treatment path for FL that everyone can agree on. That's partly because FL patients present differently, but also because all of those treatments work, so oncologists just go with what they've always used.

So there's lots to debate, if two oncologists are looking to have a friendly debate.

At this year's "Great Debates" (which happened about a week ago), the FL debate feature Dr. Peter Martin of Weill Cornell and Dr. Caron Jacobson or Dana Farber. The debate centered on Relapsed FL and CAR-T. Dr. Martin's presentation was called "CAR-T Cells Should Be Rarely Used in Relapsed Follicular Lymphoma," while Dr. Jacobson's was "CAR-T Cells Should Be More Often Used in Relapsed Follicular Lymphoma." Pretty straightforward.

Unfortunately, I don't have access to Dr. Jacobson's talk, but I do have an interview with Dr. Martin, where he summarizes what he said at "Great Debates." It's an interesting talk, and worth the 5 minutes it takes to view it (or read the transcript, both of which you can find here.)

I'll give you a summary. Dr. Martin's role in this debate is to argue in favor of "all of the other treatments" besides CAR-T, which seems to me to be the easier side to take. But he focuses in particular on 3 treatment options (and remember, these are for relapsed FL, not for first treatment). Traditional chemotherapy is not one of the options -- "we're al moving beyond that," he says.

The first of the three is R-Squared, or Rituxan + Revlimid (also known as Lenalidomide). In its favor is the fact that we have data from two large trials now, so we know a lot about side effects and effectiveness. As he says, R-squared will work for between 2 and 5 years on average, and it's well-tolerated.  A good option.

Second is Tazemetostat, an EZH2 inhibitor. It works especially on B cells, keeping them from growing, which makes it very well-suited to FL. About 20% of patients have a mutation in EZH2 that makes Tazemetostat a very good option, and it has very few serious side effects. For patients who have the particualr mutation, t can be very effective, especially given the low side effects.

Finally, and "most exciting," according to Dr. Martin, are the bi-specifics. He compares them especially to PI3K inhibitors, saying bi-specifics are geared toward the same population as those who tried the PI3K inhibitors, but the bi-specifics are twice as effective. They can be tricky to administer, and their most serious side effect is Cytokine Release Syndrome. But bi-specifics are also (like Rituxan) open to combinations with other treatments, which could increase effectiveness. 

It's interesting to me that this once again comes down to bi-specifics vs. CAR-T, but that's not a surprise.

What's most important is this statement from Dr. Martin: "I think we're at a very fortunate time in the history of follicular lymphoma to have a number of excellent options."

That's absolutely true, and the most important take away from this "great debate." We do have some excellent options, and more likely on the way.

I'm going to keep an eye out for Dr. Jacobson's talk on why CAR-T should be used more often. She's great, and I'm sure it will be worth sharing. 

But for now, we can remember that we have some other options, and they're very good.

Cannabis and Cancer

I saw an article a few days ago that caught my attention. It's from The Guardian, written by an oncologist from Australia, and it's called "Patients keep asking if they should take cannabis for their cancer. The answer is still no."

That title -- with it's "No" at the end -- reminded me of a sign that I saw once in a doctor's office. The doctor was a pain specialist, and I was there with a loved one. The sign said, in big letters, "If you are using marijuana for any reason, WE WILL NOT TREAT YOU!"

Those are both very strong statements from doctors, and they show clearly how against cannabis use some doctors are. 

I remember asking the second doctor (the one I had taken a loved one to see) why he was against marijuana use. "Are you using it?" he asked me and my loved one. "No," we said, which was true. "Good," he replied. And that was the end of the conversation.

That doesn't seem very helpful from a doctor, especially if they have such strong feelings about it. A sign like his should open a conversation, not shut it down. The whole interaction was, unfortunately, pretty typical of this doctor.

The first doctor, the one who wrote the article linked above, is a little less dramatic about the whole thing, and I think her article is worth reading. She also has strong beliefs, but is also clear about why (there is little evidence that cannabis helps with pain, nausea, sleep, or other cancer-related problems, at least in the research that she lays out). But she also links to the ASCO document that came out about a month ago, called "Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline."

The ASCO recommendation are pretty much what the author has to say, providing a "nonjudgmental" approach to patients, because patient use of cannabis has "outpaced the research." In other words, up to 40% of cancer patients are using it, whatever the research says.

And the problem is that there is so little research. Blame this on marijuana remaining a Schedule I substance in the United States, meaning it is considered to be among the most dangerous, addictive drugs we know. As a Schedule I substance, there are sever limits on the kinds of research tat can be done on it. It's been a catch-22 for a very long time -- there isn't enough research to show that it might have benefits for people, but there can't be more research because it's considered dangerous.

An FDA panel has suggested that it should be moved to a Schedule III substance, but so far that hasn't happened.  

I'm fond of ASCO, as you all probably know, and their guidelines make sense to me. 

There is no evidence that cannabis can cure any type of cancer. That might not be the case if and when it goes through more clinical trials, but for now, there's no evidence. I would never suggest cannabis in any form be used Alternative Medicine -- in place of an approved, tested treatment for cancer. I'm not a fan of Alternative Medicines. 

But Complementary or Integrative Medicine? That's a different story. There is some evidence that some patients do get some benefit from cannabis use, whether for nausea, pain, sleep, anxiety, or other issues. If they get some benefit, and they obtain the cannabis legally, then what's the problem? Even if the positive effects are psychological rather than physical, there's a benefit there. 

I hope oncologists are open to the conversation, and are clear about the ASCO guidelines and what they say -- cannabis is not a cure-all, and it can do some good, but doesn't work for everyone and does have some side effects that need to be considered. You can say that about any substance, and any Integrative practice. 

I can't offer any experience with this -- I've never used cannabis for anything related to cancer. But I'd be very interested to hear about some of your experience, especially if it's used under a doctor's care (and it probably should be, just as your doctor should know about anything you take, from blood pressure meds vitamin D). I'd like to know if it's really as popular as research suggests, and if it really does work for people.

Share your stories if you're up for it.

 

CAR-T 2.0?

A small pharma company announced today that it was submitting an Investigational New Drug (IND) application to the FDA for what they are calling "CAR-T 2.0," a newer, better version of CAR-T (or so they hope).

The treatment is called SynKIR-310, and the phase 1 trial will be patients with relapsed/refractory B-cell Lymphomas, including Diffuse Large B Cell lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, and Marginal Zone Lymphoma.

Their treatment includes a couple of differences when compared to current CAR-T treatments. They call theirs KIR-CAR, the "KIR" being "Killer-Cell Immunoglobin-like Receptors."  These help to regulate a type of immune cell called a Natural Killer (NK) cell. NK cells are a type of lymphocyte, like B cells (which turn cancerous in FL) and T cells (which is what CAR-T uses). NK cells work differently than B and T cells, which need exposure to a threat before they can eliminate them. Basically, B and T cells have to learn that a threat (like a virus or a bacteria) is a threat. NK cells can recognize cells that are damaged by disease (like cancer) and eliminate them, and then send signals to other cells that there is a problem. 

KIR-CAR is also different in that it targets a different type of protein than CAR-T usually does. CAR-T usually attaches itself to the CD19 protein, while KIR-CAR will attach itself to something very similar. 

The upshot of this, if all goes according to plan, is that SynKIR-310 will allow T cells to not have to work as hard as they do with CAR-T, meaning it will be effective longer than current CAR-T is (for some patients, CAR-T is very durable, but for about half, it stops working after a year or so, if it worked at all).

I say "if all goes according to plan" because, of course, this is very new. It has been effective on animal models, but this IND application will mean it will be tried on humans for the first time in a trial. If you follow clinical trials over the long term, you now that a pretty small percentage will ultimately end up in the doctor's office. 

Still, this is worth mentioning because it is a really good example of the kind of innovative research that is happening to make CAR-T even more effective than it is. It would be wonderful if this trial was successful and it moved on to bigger tests. 

Early, but definitely one to keep an eye on. 

Cancer, Royalty, and Minding One's Business

I've been thinking about cancer a lot lately.

That's no surprise. There hasn't been a day in 16+ years that I haven't thought about cancer. It's a side effect of being a cancer patient, as well as a blogger who needs content.

But I'm also keeping an eye on a couple of other folks who both have cancer. They are people that I work with. I've known them for years, though I wouldn't say I'm personally close with them. Their diagnoses have an effect on my job, so they told me about it before they told most people. They also know about my own diagnosis from years back, so I think they trust me to be sensitive about theirs.

Both have been in treatment for several months. I try to check in with them every few weeks. Just an email saying "I'm thinking about you. I hope you're doing OK." 

One of them writes me back with updates -- very detailed updates, sometimes as detailed as a medical chart. This colleague also asks lots of questions, about my treatment, my experiences, my feelings. We don't have the same diagnosis, but cancer patients share a lot of things anyway. As you probably know, it's comforting to have someone else who has been through it all say "Yes, I felt that way too." 

The other colleague doesn't usually respond. When I do get a response, it's not really about the details -- more of a general "Had a doctor's appointment last week and things are going OK." For this colleague, it's the second time around. The cancer was first diagnosed a few years ago, and now it has come back. But the funny thing is, I have no idea what kind of cancer this colleague was diagnosed with. They have never shared it. Unlike the first colleague who gives me a full medical chart of detail, this one has always been very private about their personal life, and they give me almost no detail at all. Not even the type of cancer.

And you know what? That's just fine.

That's what I've been telling myself as I see so much news about the British Royal Family. I'm not a "royal watcher," though I did enjoy watching The Crown. Most of what I read about their situation has come from cancer-related websites. 

In case you don't know what I'm talking about, here's a summary: In January, King Charles announced that he was being treated for an enlarged prostate. About the same time, his daughter-in-law, Princess Catherine, announced that she was having abdominal surgery. Eventually, the King announced that he was diagnosed with cancer. And recently, the Princess also announced that her surgery resulted in a cancer diagnosis.

Neither of them has announced the type of cancer they were diagnosed with. The Princess said she has been in treatment with "preventative chemotherapy," but hasn't said what type. 

And you know what? That's just fine.

I've complained elsewhere that I really wish celebrities would give more detail about their diagnoses. I am particularly annoyed when famous people announce "I have been diagnosed with non-Hodgkin's Lymphoma," and leave it at that. Because then I have to see al of the articles that tell me the survival rates for NHL without being clear that NHL isn't really a disease, but a name for about 60 other diseases, ranging from very slow-growing to incredibly aggressive, to the point where anything you say about "NHL" is meaningless. So I wish celebrities would give us some more detail. I feel like if we have to watch them go through the cancer experience, some of us would like to know just how relevant it is to our lives. If someone famous has Follicular Lymphoma, I want to know how much their very visible diagnosis reflects my own.

And then I very quickly push that out of my head.

Because it's their experience, not mine, and it's none of my business. 

As I said, I'm not a "royal watcher," but I do get a sense of how complicated their situation is. As a royal family, they have a different position than most celebrities. And if The Crown is accurate (and I know it's ultimately fiction), they also are very careful in managing their image, for reasons that may or may not be valid. And of course, Princess Catherine is a young mom, and needs to be mindful of her children and how they are experiencing all of this (I've been there, too -- The Princess is two years older than I was when I was diagnosed, and her kids are all within a year of how old my kids were at the time). 

So The King and The Princess are dealing with cancer while they are also dealing with their responsibilities to their families and their country. I don't envy them.

But in the end, whatever their responsibilities, whatever their decisions, the same thing is true for them as it is for all of us:

There's no right or wrong way to experience cancer.

Even for those of us who might be going around for the second or third time with cancer, it's still a new experience. And there's no playbook for this, no instruction manual, no To Do List. We make it all up as we go along.

And that's OK. 

Even if we look back later on and wish we had done things differently, the decisions we make at the time are the ones we are making based on the information we have and our needs at the time. If we decide to share all of the details with the world -- even starting a blog -- that's great. If we decide to keep it all inside and not share any or all of the details? That's OK too.

As for King Charles and Princess Catherine? They can tell us whatever they want, or keep the details to themselves. In the end, they are cancer patients, separate from their lives as Royals, and their only duty is to themselves and their families.

I hope you are all doing well, and feeling like the decisions you have made have been the right ones. 

Because they have been.

FDA Denies Approval for Bispecific (For Now)

The FDA has denied approval for the bispecific Odronextamab -- for now. In giving the denial, the FDA pointed to problems in the trial, rather than concerns about its safety or effectiveness. 

Some background: Odronextamab is a bispecific, meaning that it works in two parts. It is a monoclonal antibody, like Rituxan. (I keep referring back to Rituxan when I talk about monoclonal antibodies, because it's been around for so long and is so widely used in Follicualr Lymphoma that I assume most readers know what it is.) In fact, it attaches to CD20, the same protein on the surface of B cells that Rituxan attaches to. But as a bispecific, Odronextamab also attaches to a T cell, an immune cell that can help kill off the cancer cell when it comes in close contact with it. If you've been reading the blog for the last year or two, you know that bispecifics are one of those treatments that tend to get oncologists very excited.

Odronextamab (which was known as REGN1979 before it got its official name) was granted accelerated review last October by the FDA. As you may know, accelerated review means the FDA will look at a smaller set of data (maybe from a phase 2 trial instead of a larger phase 3 trial) and make a decision in a shorter amount of time (usually about 6 months instead of about 10 months). They usually grant this faster review because the treatment will provide something that is not currently available to patients, and it will help a larger number of people if they can get access to it sooner.

However, accelerated review is also provisional review. Approval will allow the maker of the treatment to make it available, but they also have to keep up their clinical trials and submit data to show that it really is as safe and effective as it seems in that shorter amount of time. 

For Odronextamab, the original application was based on data from phase 1 and phase 2 trials. The results from those trials were strong. In phase 2 trial, patients with Follicular Lymphoma had an Overall Response of 82% and a Complete Response of 75%. The treatment was durable, with a median duration of response of 20.5 months and median Progression Free Survival was 20 months. Safety was decent, though 100% of the 131 patients with FL experienced side effects, with 78% of them experiencing grade 3 (serious) side effects, including Cytokine Release Syndrome (in over 50% of patients in the trial), low blood cell counts, diarrhea, fever, and joint pain. 

Importantly, the denial of the application is based on numbers of patients, not on concerns about safety or effectiveness. Basically, the FDA wants to see how the treatment works in more patients. They aren't denying the application forever, just until more data can be collected.

Of course, that's not what the maker of Odronextamab wanted to hear. There are actually two types of trials required, one focused on dosing (making sure the optimal amount of the treatment is given) and the other focusing on confirming the results f the earlier trials. The company behind Odronextamab says it is actively recruiting patients for these trials and is working with the FDA to have a new schedule later this year.

A couple of things seem significant to me.

First, this seems like a clear signal that the FDA really is getting more serious about accelerated approvals. With problems coming up after a quick approval, the agency wants to make sure treatments are safe and effective. In this case, they don't seem to be switching to an emphasis on Overall Survival, with all of the complications that would come with it (as William and Peter pointed out in their comments to my post earlier this month). They don't necessarily want new or different data here, just more of it. That seems like a reasonable approach.

Second, this confirms the importance of clinical trials, and patient participation in them. New treatments can't be approved without large trials, and large trials need willing patients. As you meet with your oncologist, add that question to your conversation -- are there clinical trials that would be appropriate for me, if and when I need treatment again? It's important to know what might come next for you, and important to all of us that new treatments have the data that they need to be approved (or not approved, which is just as important).

I'm sure there will be updates about Odronextamab in the very near future -- maybe as soon as a couple of months from now at the ASCO conference. But we'll definitely hear something by the end of the year about what the plans are for trying to get permanent approval.

Drug Name Tournament

Here's a kind of fun item for you Cancer Nerds: the website Fierce Pharma is holding a "drug name tournament" for the next few weeks.

Some background for you first. In the U.S., we are just beginning the period known as "March Madness." College basketball is a big deal to many people in this country, and this week, the NCAA tournament begins. This involves 64 basketball teams that will play each other to determine who the national champion is. (I know it's actually 68 teams, but we're not going to complicate this any more than necessary.) And there are actually two tournaments, one for men's teams and one for women's teams. You can find a decent explanation of it all here.

There are lots of opportunities to get into a "tournament pool" where you have to guess which teams will win in each round of the tournament, all the way to the national champion. There are "office pools" set up among people who work together, and lots of chances to play against strangers online. Participating involves "filling out a bracket," guessing the winner of every game before the first game has even started. Sometimes there is light gambling involved, with the participants putting up a little money and the winner getting all of it. 

It is notoriously difficult to guess every winner of every game in the tournament. This is because of the way the tournament is set up. It doesn't involve the best 64 teams in the country. Instead, some teams get in because they have won their conference or group, and so a few teams are very small and not well known, and no one expects them to win against bigger, better-known teams. But these small teams do occasionally win, bringing up lots of David vs Goliath comparisons. It can be fun to get into a pool, unless your teams lose early.

Because not everyone is basketball fan, there are also lots of alternate "March Madness" tournaments around at this time of year. Everything from best Beyonce songs to best characters from Pride and Prejudice. You're not guessing the winners of games; instead, you're guessing which choices you think will be the more popular in the bracket.

So back to Fierce Pharma. They are holding a "drug name tournament." Last year, they had a tournament where readers picked the best advertising campaigns from pharmaceutical companies. this year, they're going with drug names. They have chosen 64 drugs out of the 92 that were approved by the FDA in 2022 and 2023, and put them into a bracket, NCAA tournament-style.

Their goal isn't to have people choose the "best" drug, but rather to choose the best name. It's more about marketing than effectiveness (since that is Fierce Pharma's focus). In making choices, they'd also like participants to add what they think the drug name sounds like. Fierce Pharma has given their own example for each of the 64 names. (For instance, one of the drugs is Jesduvroq, which is meant to help with low red blood cell counts due to chronic kidney disease. They think Jesduvroq sounds like something you would say "when you hit your finger with a hammer, but it’s in front of your children so you’re trying not to swear.")

For me, as a Cancer Nerd, it all sounds kind of fun. Drug names are always a little strange, though with some very serious work behind them, and this tournament pokes some gentle fun at them. I like that.

And if you're wondering if any Follicular Lymphoma treatments made the cut -- YES! There are two of them.

The first is Lunsumio, the bispecific that is also known as Mosunetuzumab. Fierce Pharma says the name Lunsumio sounds like a Japanese wrestler.

The second is another bispecific, Columvi, also known as Glofitamab. This was approved by the FDA for Diffuse Large B-cell Lymphoma, though it includes DLBCL arising from transformed FL. (There are some additional clinical trials for FL going on as well.) Fierce Pharma says Columvi sounds like an ancient Roman detective. Slightly more creative than their Lunsumio comment.

So good luck to all of you participating in March Madness tournaments, whether it's for basketball or something else.  Let me know if you do well in the Fierce Pharma competition.

A Follow-Up on Secondary Cancers and CAR-T

 A follow-up to the news from a few months ago that the FDA was issuing a warning about CAR-T causing secondary cancers. After reports of patients who had received CAR-T developing T cell cancers, the warning was issued in January. 

The concern was that the patients were developing T cell cancers specifically. CAR-T, of course, currently made for each individual patient who receives the treatment. T cells are removed from the patient, manipulated to recognize cancer cells, and put back into the patient. Because the T cells are manipulated, the concern is that the process might go wrong in some way and make the cells cancerous. There are several varieties of CAR-T (it's a general category, not a specific treatment, though I know I often write about it as if it is one thing and not many). Each one has a slightly different way of manipulating the cells. But they do have the same general process.

Since then, there has been some research on just how common secondary cancers are among CAR-T patients. This morning, the journal Blood published "Second Primary Malignancies After Commercial CAR T Cell Therapy: Analysis of FDA Adverse Events Reporting System (FAERS)." I can't see the article, or even a summary, but ASH, which publishes Blood, put out a press release about it, which is very helpful.

The researchers who wrote the article looked at the FDA's Adverse Events Reporting System, or FAERS, and catalogued the number of times CAR-T patients reported developing a new cancer. The FAERS system is voluntary -- an adverse event, or side effect, can be reported by a doctor, or a patient, or by someone else. So it's possible that some of the adverse events were reported more than once, by both a  doctor and a patient. And it's very possible that an adverse event wasn't reported at all.  So it's important to keep in mind that these numbers are not comprehensive.

That said, they do offer at least a small picture of how common secondary cancers are in CAR-T patients.

The researchers looked at a total of 12,394 adverse events that were reported about CAR-T patients. They found that 536, or about 4.3% of the adverse events reported were secondary cancers. So, to be clear about this -- of all of the adverse events (or side effects) reported voluntarily, 4.3% were new cancers. And to be even more clear -- there isn't necessarily a clear connection between the treatment and the new cancer. It's certainly possible, but not definite.

I'll give you an example of how this works. I received Rituxan 14 years ago. I was diagnosed with a secondary cancer (a skin cancer) a few months ago. Did the Rituxan cause the cancer? Maybe. Did my immune system cancer cause it? Maybe. Did my never wearing sunscreen as a kid cause it? Maybe. Was it a combination of al three? Maybe.

It's really difficult to connect a secondary cancer to a previous cancer treatment. But there can be a comparison to other populations who didn't get cancer treatment, and compare how common the cancers were.

So which cancers were most common among CAR-T patients? Leukemia was most common -- 2.7% of all of those 12,394 adverse events were leukemia. Skin cancers (the most common secondary cancers among all cancer patients) were 0.4% of the adverse events.

And T cell cancers, the type that are most concerning? They amounted to just 0.1% of all of the adverse events reported. 

I want to be clear here -- I'm not saying here's no danger of getting a T cell cancer. The fact is, I don't know. And I can't say for sure what the odds are of getting any secondary cancer. The FAERS system only gives a partial picture of things. 

I'm not an oncologist or a cancer researcher. If you're concerned about secondary cancers -- if you're concerned about any adverse events or side effects -- the best person to talk to about it is your own oncologist. They'll have a much better idea of what the risks and rewards are for any treatment you might have.

And that should be a part of any conversation you have about treatment, anyway, whether you are in need of one immediately, or you're thinking about the future and what might happen when you do need treatment. It's easy to trust your doctor when they have a suggestion for treatment (and I hope you have a relationship with your oncologist that does allow you to trust them). But make sure you know everything you can before you make that decision together.

New FDA Approval for R/R Follicular Lymphoma

Yesterday, the FDA granted accelerated approval for the combination of Zanubrutinib and Obinutuzumab for Relaped/Refractory Follicular Lymphoma patients who have had at least two previous treatments. this is good news -- we have another option.

Zanubrutinib is an inhibitor. It's different from the PI3K inhibitors that have been approved (and then pulled) in the last few years. But it works on the same very general principle of inhibiting (or stopping) a process from happening that cancer cells need to grow and live. 

Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor. BTK is an enzyme that plays an important role in B cells developing. B cells are of course the cells that turn cancerous in Follicualr Lymphoma and a bunch of other blood cancers. So stopping their development is a way of holding off the cancer  from growing.

Obinutuzumab is a monoclonal antibody, like Rituxan, but with some differences. It's the "O" in a treatment like B-O or O-CHOP, and probably the most successful attempt at an alternative to Rituxan. 

The accelerated approval is based on the results of a phase 2 trial known as the ROSEWOOD trial. In this trial, patients were given the Zanubrutinib-Obinutuzumab combination and the results were compared to patients who were given just Obinutuzumab. The comparison involved looking at two statistics -- Overall Response Rate and Duration of Response. 

The researchers found that 69% of the Z-O patients had a response (whether it was Complete or Partial), compared to just 46% of patients who had just O. As for Duration of Response (DOR), after a median 19 months, the median DOR was not yet reached for the Z-O combination. In other words, more than half of the patients in the trial were still getting a response after that time. For the O patients, the median DOR was just 14 months. 

As for side effects, there were no surprises. Zanubrutinib had already been approved for other blood cancers, and the Z-O combination didn't result in any new or worse side effects than have already been reported. These include diarrhea (18.2% in the Z-O patients and 16.9% in the O patients), fatigue (15.4% and 14.1%), and fever (13.3% and 19.7%).

As I have said before, there are several BTK inhibitors already approved for other blood cancers, but this is the first for Follicular Lymphoma. It's interesting -- it would make sense that a BTK inhibitor would work on FL, but so far, none have been successful, including Ibrutinib, which was a game-changer for CLL patients. Not sure why. But this combination seems to be working for some patients.

And it needs to be noted that this comes form an accelerated approval. Obviously, OS was not even considered as a primary endpoint or way of measuring success. That's likely because this is an approval for R/R FL, and finding a treatment that keeps patients from needing further treatment is the priority. But as an accelerated approval, the combination will still need further clinical trial testing to get permanent approval. We'll keep an eye on that.

No one is really talking about it much online just yet, maybe because Zanubrutinib is already pretty well known, so there's less excitement. But it will be interesting to see how often this gets prescribed from here. If any of you have a conversation with your oncologist about this, please let me know. I'd love to hear what an expert thinks.

Stay well.

Will the FDA Change the Way They Approve Treatments?

The website BioSpace posted a really interesting article a coupe of weeks ago called "How Will FDA’s Pivot to Overall Survival Affect Cancer Drug Development?" 

In my last post, I mentioned that I was a little surprised that the FDA was considering accelerated approval for the bispecific Epcoritamab, and that I had been doing some reading lately about the FDA potentialy changing the way they approve cancer treatments. The BioSpace article is a nice summary of the kind of things I have been reading.

As the article points out, over the summer, there was a workshop at the American Association for Cancer Research conference, co-sponsored by the FDA, that looked at the issue of Overall Survival (OS) in cancer clinical trials. OS is the gold standard in clinical trials -- if the developer of a new treatment can show that it keeps patients alive longer than currently available treatments, it has an excellent chance of being approved (assuming the side effects are not awful). As patients, this is what we want, too -- a treatment that will keep us alive longer.

The problem is, OS is hard to measure in a reasonable time. As cancer treatments have improved over the years, OS has gotten larger. That means newer treatments have more work to do. In other words, if a new FL treatment was going to be approved, it would need to show a better OS than what we have now -- maybe 15 or 20 years. But in order to do that, a trial would have to last at least that long. How else can you show that patients will survive for 20 years without following them for 20 years? 

The answer is to use a "surrogate endpoint." That means finding a different measurement that would signal that OS will be long. For most trials, that surrogate endpoint is Progression Free Survival (PFS). This is a measure of how long a patient goes before the cancer comes back or gets worse. The idea is, if a new treatment can show a longer PFS than current treatments, that's good enough to approve it. 

And that's where there are problems. PFS is often measured in just a few years, maybe even in months -- certainly fewer than the 8 or 10 years that we might get for an OS in Follicular Lymphoma. For some cancers, PFS can be measured in months. But the makers of new treatments don't want to wait that long. They want their treatments to be available as soon as possible, so they can begin making back the money they put into the development of the treatment, plus a big profit.

To be fair, it's not just the drug makers who want the treatment available quickly -- patients want that, too. And that's why the FDA developed accelerated approval procedures. If a new treatment can show an improvement in PFS, it can potentially get approved based on the results of a phase 2 trial (it usually takes a phase 3 trial for approval),with the understanding that a phase 3 trial will come later. Final approval will depend on the phase 3 trial results.

But, again, the problem is that approving a treatment too soon can create some problems. The biggest one is, there may be side effects that come out years after approval. And this happens, unfortunately. In Multiple Myeloma, a treatment was withdrawn a few years ago by the FDA after accelerated approval because over time, it was found that the treatment had a significant increase in the chance of death. And of course, if you've been reading the blog for a while, you know that a similar (though not so drastic) issue came up with PI3K Inhibitors for FL. Problems come out over time.

Some FDA officials (according to the article) have signaled that they would like OS to be more commonly used, with less of a reliance on PFS.  Ideally, a treatment would be approved after there was an Overall Survival benefit, with no safety issues, based on a randomized clinical trial. That is, there would be a fairly large trial with two groups of patients. One group would get the currently used treatment (called the "Standard of Care") and the other would get the new treatment. They would be followed for potentially many years, until an OS was determined. And then the data would be submitted to the FDA for approval.

Will that happen? It's hard to say. The FDA has a tough job. They have to make decisions based on the best interests of patients. But the question is -- is the best interest of patients to have a treatment become available as soon as possible? Or is it to make absolutely sure that it increases survival?

It will be very interesting to see which direction the FDA goes in. Certainly, based on the Epcoritamab decision last week, they are still considering accelerated approval and not relying on OS completely. And in my opinion (for what it's worth -- I'm not a doctor or a cancer researcher), it will probably be something they consider for each individual application. Some cancers are so rare and have so few treatment options that it will be worth the risk to approve something based on PFS and get it into doctors' hands as soon as possible. And for others, maybe less rare and with other options already available, maybe they will be more cautious and want to see the full trial results. 

The question for us is, where does Follicular Lymphoma fall on that scale?

 

Epcoritamab Gets FDA Priority Review

A quick bit of news: The FDA granted Priority Review status to Epcoritamab for Relapsed/Refractory Follicular Lymphoma.

Epcoritamab is a bispecific antibody. As a bispecific, Epcoritamab acts like a monoclonal antibody like Rituxan, by seeking out and attaching to a protein on the cancer cell (in this case, it attaches to the CD20 protein, just as Rituxan does). But then it dos something else -- it attaches to a protein (CD3) on a T cell, a kind of immune cell. By bringing the T cell close to the cancer cell, it helps the immune system work on the cancer.

The Priority Review means that the FDA thinks Epcoritamab will offer significant improvements in either safety or effectiveness over what is now available for R/R FL patients. It will make a decision in 6 months, rather than the usual 10 months, so it is likely to decide whether or not approve by June 28. 

The Priority Review is based on the phase1/phase 2 EPCORE trial. These results were presented at the ASH convention a couple of months ago. The results of that trial were very good; the Overall Response Rate was 82%, with a Complete Response Rate of 63%, comparable to Mosunetuzumab, the bispecific that is currently approved for FL patients. 

One thing that I find especially interesting is that they are considering approval based on a phase1/2 trial. Though it's fairly large for an early trial (128 patients), the FDA has also been sending signals that they want to slow down on accelerated approvals. They'd rather see full, phase 3 randomized trials instead, which are more reliable and give more time for potential side effects to come to light. I've actually been working on a post on that very subject; I may have to speed it up and get it on the blog soon.

Regardless, this is good news, assuming that everything goes well with the review. As I have said several times before, bispecifics are one of the treatment types that seem to get Lymphoma specialists most excited (and I include my own oncologist in that group). So another bispecific option would be great for all of us. 

More to come, I'm sure -- I'll keep an eye out for news and commentary about Epcoritamab, and share any good stuff I see. 

Survivorship Research

I've been thinking a lot about the idea of "survivorship" lately. 

In cancer terms, survivorship is what happens after treatment is finished, particularly after treatment has been successful. I've known lots of cancer patients who were just kind of on their own at that point (or maybe who felt like they were on their own).  Once the treatment is done, there's no need for a doctor anymore, right? Except for a couple of visits to make sure everything is still OK?

That was certainly the attitude for a long time. But more and more, cancer centers are creating and promoting "survivorship centers," with specialists who focus on helping out patients after they are "done." As many of us know, after a successful round of treatment, there is still a whole lot to deal with -- the many, complex emotions that come with cancer; physical changes, big and small; financial difficulties with lingering bills. There's a lot to deal with, even after the cancer cells are gone. It's great that more and more cancer centers are recognizing that, and equipping them with social workers, psychologists, nutritionists, pain specialists, and others who can provide some help. 

So how do all of these folks know what to do for cancer patients to help them? That's where survivorship research comes in. The ASCO Post has a nice piece about this subject from two people who know a lot about it -- the lead of evidence-based survivorship supportive care and the director of cancer survivorship and supportive care programs at the University of Miami Sylvester Comprehensive Cancer Center.

They  point out the many, many issues that Survivorship Clinics help patients with -- physical, emotional, and financial -- that I mention above. Add to that short list a few more -- issues with pain, fatigue, sleep, attention and memory, sexual function anxiety, depression. All of those things are very common problems for cancer survivors. It's good to know how common they are. I think a lot of cancer patients have difficulties and think "It's all over now. The cancer is gone. Is all of this in my head?" Probably not. It's good to know that there are places to go to get help.

And here's the good part. Survivorship research sometimes gets its data from clinical trials. Just like developing treatments, survivorship benefits from patients who are willing to be a part of a study. And just like trials for new treatments, survivorship trials often have trouble recruiting.

The ASCO Post article doesn't recommend any specific survivorship trials, but they do recommend a couple of places to look if you're interested in participating. The first is by looking at the National Cancer Institute's database of clinical trials and/or at the U.S. government's clinicaltrials.org site. Both are fairly easy to use. (And they're great for seeing all of the Follicular Lymphoma trials near you, not just the survivorship ones.)

The second is by looking at the websites for different patient support organizations. I've done the NHL search for you, so you can find a list of lymphoma organizations here. Some of them may be participating in, or helping to recruit for, survivorship trials. 

Now, I've talked about the importance of clinical trials many times on the blog, and I always try to find out what my oncologist is excited about in research, and whether my cancer center is doing any trials on it. But also know that cancer patients can be very hesitant about participating in a trial, since the treatments are unproven (that's the whole point f a clinical trial).  One of the great things about survivorship trials is that, in some ways, the stakes are lower. If a patient is worried about side effects of a new drug, the interventions for many survivorship trials do not involve physical side effects. Here's an example from the Mayo Clinic in Minnesota (which has an excellent survivorship program) -- breast cancer survivors who are taking endocrine therapy are in a trial to see if motivational interviews and text messages will help them to remember to continue their therapy. There may be some emotional side effects to a study like that, but not the physical ones that scare off lots of cancer patients from participating in a trial. (And just to be clear, it's worth talking to your oncologist about those fears. They may be fears about nothing, and a good talk with lots of honest questions might calm a lot of those fears.) 

I also know that, for many Follicular Lymphoma patients, the whole idea of "survivorship" can be a tricky thing. The idea that FL is incurable is always in our minds. What does it mean to be a "survivor" if there's a chance that it might come back soon? Is it worth going through the things that "survivors" go through?

I would say yes, absolutely. The National Cancer Survivors Day folks tell us that anyone who has ever been diagnosed and is still alive is a survivor. There's no 5 year waiting period or anything like that. Different survivorship trials might have certain criteria to participate, which is understandable. But being finished with active treatment, no matter what the status, should be enough to make it worth looking into some trials. (Here's another example -- Sloan Kettering in New York has one comparing Music Therapy and Cognitive Behavioral Therapy to treat anxiety in cancer survivors.)

And your status as a survivor certainly opens the door to whatever survivorship benefits are available to you at your cancer center. And if your cancer center doesn't have a survivorship clinic, or you go to a community oncologist in a smaller office, then ask if there are any services for survivors. I'm guessing they're have some suggestions.

Most importantly, be sure to continue to take care of yourselves, physically and emotionally, long after you are finished with any treatment. There's help for you if you need it. 

Upcoming LRF Event

As you may know, I like to promote some of the webinars and workshops the the LRF (the Lymphoma Research Foundation). I've been able to attend them in person and online, and I think they're great. They usually involve one or more oncologists giving a presentation, and then time for questions and answers. Sometimes the topics are very general, and sometimes they are very specific. But the LRF usually does a great job of finding speakers who know the latest research on Lymphoma, and who can explain things clearly. 

There is a big  LRF event coming up that is worth attending -- the "National Lymphoma Workshop: Understanding Lymphoma Basics and Current Treatment Options."

This a virtual workshop, so everything is online. The date is Saturday, March 16, and it runs from 9:30am to 1:30pm. The first part of the webinar is a general overview of Lymphoma. After there, there are individual sessions for different types of lymphoma, including one for Follicular Lymphoma, led by Dr. Laurie Sehn of the British Columbia Cancer Agency. (Dr. Sehn was one of the panelists from the video series that I linked to a couple of weeks ago. She knows her stuff.)

After a break, there are two more general sessions -- one on Nutrition with Peter Adintori of Memorial Sloan Kettering Cancer Center, and one on Integrative Medicine with Dr. Santhosshi Narayanan of MD Anderson Cancer Center. These should be very good. I'm especially interested in the Integrative Medicine session, which will look at the ways traditional cancer treatment can be supplemented with other practices. Always a fascinating topic.

You can use the link above to see the full agenda and to register for the workshop. As I said, the LRF does a good job of finding speakers who can explain things well. This workshop should be the same way.

I hope some of you can find time to attend, and get something out of it.

How to Read Survival Statistics

A couple of weeks ago, a reader made a comment about Overall Survival, and I gave a brief response. But I know there are some new readers here who were diagnosed fairly recently, so I think it's a good time for a reminder about "Overall Survival" and what it means.

It's especially important for folks who are newly diagnosed. For most of us, when we heard those words -- "You have cancer" -- our minds immediately went to some variation of "How long do I have?" Survival statistics serve as a kind of easy way to figure out how worried we should be. 

But survival statistics don't tell us anything about our own situations. It's easy to read a statistic that says the survival rate for a cancer is X years, and say "Well, I only have X years left." That's just not true. That's not how statistics work.

I'll use myself as a quick example. When I was diagnosed in 2008, the Median Overall Survival for Follicular Lymphoma was thought to be 8-10 years. Here I am, 16 years later. 

One of the problems with that 8-10 year statistic is that it was probably already outdated when I saw it. At that point, Rituxan had been in use widespread for FL for about 10 years (it was approved by the FDA in 1997). Rituxan is generally credited with increasing the Median Overall Survival, which had probably already done by the time I was diagnosed. But that 8-10 year figure was from the last large study of  FL survival, done before Rituxan, and looking backwards anyway, measuring the survival rate of people who were diagnosed in the 1980s. 

So that's the first danger with looking at survival statistics and thinking they are a measure of your fate -- they're probably outdated, maybe very outdated, and don't take into account any newer treatments.

As for the other problems, let's look at the term "Median Overall Survival," which is the official term for survival statistics. 

First of all, it's important to remember what "Overall Survival" is measuring. This statistic looks at death from any cause, not from the disease being considered. A statistician looks at a bunch of records of cancer patients, marks which have died, and notes when it happened. Those deaths aren't distinguished by cause. So it includes people who died from their cancer. And people who died from complications of their treatment. But it also includes people who died from heart disease, car accidents, getting too close to wildlife at national parks -- any cause of death. "Overall Survival" simply looks at how many people died, and how long they lived after they were diagnosed.

That's especially important for Follicular Lymphoma patients. We are generally diagnosed with FL sometime in our 60's (I haven't seen a solid statistic for this anytime recently). So for a group of people who are diagnosed fairly late in life, we can probably expect a lifespan of 15-20 years. That just makes sense -- anyone at the age of 65 (whether they have FL or not) probably has a life expectancy of about 15-20 years. 

And that is indeed about what researchers put as Median Overall Survival -- about 15-20 years. In other words, as a group, we're pretty much in line with the general population.

The other important word in this formulation is "Median." That's a term from statistics. It's different from "average," because one big number can throw off an average. "Median" means the exact middle. So if you had 999 Follicular Lymphoma patients, and you lined them up based on how long they survived after diagnosis, then number 500 in that line up would be the median. (There would 499 on either side of that patient.)

Since the "median" is the exact middle, that means 499 of those patients would have a shorter survival than #500. But it also means that 499 would have a longer survival.

Think about that. If #500 has a survival rate of 20 years, that means half of us will have a survival rate of greater than 20 years. How much greater? Maybe 20 years and 1 day. Maybe 25 years. Maybe 50. 

That's especially important for us who were diagnosed on the young side. Like me -- I was diagnosed at 40 years old. That doesn't mean I can expect to only live a few more years. The patients on the right side of #500 don't have an upper limit. Statistically, I could live until I'm 90 -- a 50 year survival rate. 

(By the way, that's how long I expect to live -- at least.)

But what about those folks who were to the left of #500? That still doesn't mean anything. It includes people who didn't know they had FL until very late in their lives, maybe in their late 70s, and then had a normal life expectancy. It includes people who didn't get a diagnosis until their disease was very far along. It includes people who walked out of the doctor's office after getting a diagnosis and had a piano fall on them 5 minutes later. 

The point is this -- statistics are not destiny. The numbers that describe a group of thousands of people, especially because they are collected by looking at the past, don't tell us anything about us as individuals. Our lives are all different, and our diseases are different.

I personally stopped looking at statistics a long time ago. When I was first diagnosed, the things that threw me into a depression were almost always statistics.  Numbers seem so definite, so correct, so real. And it's very easy to get sucked up into them and take them as the truth about ourselves. But that;s just not how it works. 

So if you want some numbers, here is a good one. 

A long time ago, a reader told me that her doctor was discussing treatments with her, and how excited he was about there being so many new options in the pipeline. The doctor told her "If we can keep a Follicular Lymphoma patient alive for 5 years, we can keep them alive for 50 years."

And that conversation happened before CAR-T, before bispecifics, before R-squared. And who knows what other treatments that might be coming soon.  

If you feel yourself getting pulled down by numbers, keep that one in mind.

I hope this helps some newer folks to better understand what survival statistics actually mean, and how little significance you should give to them. And I hope those of you who have been around for a while appreciate the reminder. Numbers are not destiny.

Take care.

World Cancer Day

Today is World Cancer Day, an event sponsored by the Union for International Cancer Control. In case you are wondering what "cancer control" is, here is how the UICC defines it:

Cancer control aims to reduce the incidence, morbidity and mortality of cancer and to improve the quality of life of cancer patients in a defined population, through the systematic implementation of evidence-based interventions for prevention, early detection, diagnosis, treatment, and palliative care.

 In other words, their aim is to support cancer patients throughout the cancer experience, from preventing it from happening to making them more comfortable when they do have it. 

And so Word Cancer Day is meant as a day of awareness. As I have said in the past, I'm really not in need of awareness -- I am made of aware of cancer literally every day of my life. But cancer awareness is about making others aware, and World Cancer Day is not different from mother awareness campaigns. Making others aware means helping them prevent it, detect it, and support funding for research to get rid of it. All of that matters -- those of us who have been diagnosed know that all too well.

The theme for this year -- actually for the last three years -- has been "Close the Care Gap." The UICC wants to highlight the disparities in cancer. Not everyone is able to get screened, or diagnosed, or treated in an equal way. So over three years, they have highlighted the problem, the ways that action can be taken, and now this year,  they encourage is all to "challenge those in power." Together, we can demand that leaders prioritize cancer and its eradication.

It's a great goal, and anyone who has been unable to get what they need really understands what this theme is all about. In the United States, cancer care is often a problem because of our healthcare system, which certainly creates disparities. I'm guessing many of you have had the experience of not being able to get something you wanted or needed. But that's not just a problem in the United States. Health systems in other countries need to prioritize care, meaning some treatments aren't available to some patients. And in still other countries, some treatments that have been approved in the US or the EU are not available to patients.

So this year's World Cancer Day is about working to make those differences go away. Doing so can be as simple as clicking on the "Call to Action" link on the World Cancer Day website. Or maybe there's more you want to do. A group like the Leukemia and Lymphoma Society would welcome your help in getting our leaders to pay more attention to the needs of cancer patients.

So while World Cancer Day only lasts for one day, the need keeps on going. And there are are lots of opportunities to  help.

Of course, lots of cancer patients don't ave the energy or the resources to do what they'd like, and that's OK, too. We do what we can.

But for those of you who can, please do consider spreading awareness and getting the message out. It can only help you.

 

Treatment Options for Follicular Lymphoma

OncLive published another of their great video series a few weeks ago. I like these series -- they provide some very up-to-date information, and they usually bring in different oncologists to give their perspective for each new series.

This series is called "Recent Updates in the Treatment of Follicular Lymphoma and Mantle Cell Lymphoma." Like all of their video series, this one is meant for oncologists, not patients. But if you keep up with current treatments, it's not hard to understand.

There are 10 videos in the series, and it is structured around treatment lines. In other words, the first video talks about current treatment options for first line -- for patients who have never had treatment for their FL. Then there are videos focusing on second and third line treatment options. This series features a bunch of oncologists. There's Dr. Grzegorz Nowakowski of the Mayo Clinic, Dr. Jennifer Crombie from Dana Farber, Dr. Matthew Lunning from The University of Nebraska, Dr. Peter Martin from Weill Cornell, Dr. Laurie Sehn from the University of British Columbia, and Dr. Bijal Shah from the Moffitt Cancer Center. An excellent group.

The link above will take you to the first video, though the other nine appear right below it. (Unfortunately, this series does not include a transcript.)

The focus is on newer research presented at recent conferences, but really, the discussion is about what's been available for a while. In the first video, the oncologists talk about how they approach a treatment decision for a patient who has never had treatment. This includes watching and waiting for patients with no symptoms. For other patients, depending on their health, this could include just Rituxan, especially if the patient is older and has other health issues. But for younger, healthier patients, some type of traditional chemotherapy might be a good choice. Still other patients, who don't want chemo, they might choose R-squared.  And of course, clinical trials are always a consideration. For one of the oncologists, probably half of the FL patients she sees do not have an aggressive disease, and can watch and wait or try Rituxan. This allows more time to consider a treatment path.

The other videos in the series do talk about some of the other options, especially those that had new data presented at the ASH conference. The videos are about 5 minutes each, give or take a minute. Together, they present a pretty good overview of where we are right now in our options for treatment.

Important to consider -- these videos were recorded soon after the ASH conference in December, even though the videos themselves were posted over several weeks after that. Some of the recent issues related to CAR-T are not included in the discussion. I'm sure there will be some discussion of that in another video series.

The panelists are excited about bispecifics, and see them as a third-line possibility, though they are also seeing more evidence that they could work as first-line treatment. There is also some discussion of Zanubrutinib, the BTK inhibitor, with its surprisingly good data for FL.  

Lots of good stuff here. If you're looking for a good summary of where we are for treatment, this is a good place to be.

Take care.

New FDA Warning for CAR-T

There was some bad news for CAR-T treatments issued yesterday -- the FDA called for  "Black Box Warning" for CAR-T treatments. These would include the CAR-T treatments that have been approved for Follicular Lymphoma. 

This follows reports from November that some CAR-T treatments were leading to T Cell malignancies. In other words, with the treatment that involves changing T cells to find and eliminate cancer cells, those T cells could turn cancerous themselves. 

There's a lot to unpack here, and I'm trying to be rational about it all. 

First, the FDA's action. Issuing a "Back Box Warning" means they are adding a literal black box or border to the packaging insert of the treatment. The black box is meant to make it stand out and be noticed. The warning is considered the highest safety-related warning that the FDA gives, and it usually means that the treatment can lead to severe side effects. There are currently over 400 approved treatments, including many cancer treatments, that have Black Box Warnings, and the warnings can be changed or removed over time as new data becomes available.

The FDA warning came because a large number of patients who have taken CAR-T treatments have developed T cell cancers. In the letter that the FDA sent to manufacturers of CAR-T treatments, they said that they have become aware of this risk and that the new cancers have "serious outcomes, including hospitalization and death." How many patients have developed new T cell cancers? I can't find a definitive number, but it may be as high as 22. That doesn't seem like a lot compared to the thousands who have received treatment, but it's enough to issue the warning, especially since they develop over time. Doctors have been asked to be especially vigilant with CAR-T patients and continue to monitor them, even after they have been in remission for some time. 

The call for the Black Box warning isn't complete. The manufacturers have 30 days to respond to the FDA, with changes they will add to the labels, or a statement of why they think the label warning isn't necessary. 

So what does this mean for Follicular Lymphoma patients?

I'm not really sure. As I have said before, I'm not an oncologist or cancer researcher.

But really, I'm not sure even oncologists know at this point. It's very new, and they seem to be digesting the news (at least in the conversations I am seeing online).

Any new Black Box warning makes doctors take notice, obviously. They need to rethink the kind of risk/reward calculations that they always make when considering a treatment for a patient -- essentially, will this treatment create more problems than it solves? Every treatment has side effects, some more severe than others, some that affect certain patients more than others. That's not going to change. But they're going to have a lot more to think about.

Some interesting reactions online that I have read:

• This may lead some doctors to recommend CAR-T for older patients, if T cell cancers develop many years later, rather than younger patients who will be at greater risk.
• This may lead researchers to create "kill switches" on the T cells, so if they turn malignant, they can be more easily killed off (don't know if that's even possible).
• There is still a lack of data over the relationship between CAR-T and the new cancers. In other words, researchers are still looking to see if the T cells that were changed as part of the treatment are even the same T cells that turned cancerous. That's extremely important data to have. 
  
• At least one oncologist who I respect a lot says CAR-T will still be a great help to many of his patients, and that the new cancer is "low risk."
• Another said the rewards of CAR-T far outweigh the risks, especially since CAR-T is often used now for patients with "dire prognosis."

So as I said, I'm trying to be rational about it all. In my own case, CAR-T isn't something that my oncologist and I have discussed for me right now. Maybe that changes over time. And maybe by then, there's more data about this issue to help make a decision.

So, the same advice applies as always. Have an oncologist that you trust, and have honest conversations about treatment -- your goals, your fears, and your needs. Then make the best decision you can.

No Survival Benefit with Rituxan Maintenance

The Journal of Clinical Oncology published the results of a study a few days ago that looked at long-term benefits of Rituxan Maintenance. The article is called "Long-Term Follow-Up of the RESORT Study (E4402): A Randomized Phase III Comparison of Two Different Rituximab Dosing Strategies for Low–Tumor Burden Follicular Lymphoma." The big news from the study is that there doesn't seem to be a survival benefit from Rituxan Maintenance in low-tumor burden Follicular Lymphoma patients. 

A few things need some explaining here. 

First, Rituxan Maintenance is a type of treatment where patients first receive a treatment that includes Rituxan (also know as Rituximab and Mabthera), a monoclonal antibody. The treatment could be just Rituxan, or it could be Rituxan combined with something else (like R-CHOP or R-Bendamustine). For this particular study, the patients received only Rituxan, once a week for four weeks. The "maintenance" part comes next, after the initial treatment -- patients receive just Rituxan on a regular schedule for a certain time period. For this study, the patents recieved Rituxan every 13 weeks until they need treatment again. (Some Rituxan Maintenance studies have a different dosing schedule, like every 2 months for 2 years, and then no more.)

The idea behind Maintenance is that the regular doses of Rituxan will help "clean up" any leftover cancer cells, or any new cells that develop. It's always been kind of controversial, with some studies showing a benefit and others showing no benefit, and others showing a small benefit but asking if the additional cost and additional weakening of the immune system is worth it (Rituxan reduces cancerous B cells, which are part of the immune system, but also healthy B cells).

For what it's worth, my own treatment, 14 years ago, was 6 weekly rounds of Rituxan. I haven't needed treatment since. I do remember asking my oncologist, as we discussed treatment, if we should consider doing maintenance. Back then, he told me that there was good evidence that maintenance helped people who had received immunochemotherpay (R-CHOP or R-Bendamustine, or back then, R-CVP, which is less common these days), but less evidence that there was a benefit for people who received only Rituxan.

What seemed like the case, 14 years ago, is confirmed by this research, which looked at a long-term follow-up of patients like me, with low tumor burden, receiving only Rituxan.

I'll repeat this, because I think it's important -- this study looked only at low-tumor burden FL patients who received only Rituxan. There's a whole other body of research on patients who had high tumor burden, or who received other treatments (though they are controversial in their own ways -- you can search for what I have written about them over the years). 

For this study, 289 FL patients were divided into two groups, as I mentioned above. The first group received four weeks of Rituxan, and then no other treatment until their disease returned and got bad enough to need treatment. The second group received Rituxan, and then more Rituxan every 13 weeks until it stopped working and they needed a different treatment. 

The Maintenance group did have some benefits to their treatment. After 7 years, 83% of the patients who had received Maintenance had still not needed a second treatment. In the first group, only 63% of patients had been able to avoid treatment.

Also, some patients had their disease return, even though they didn't need a second treatment yet. After 7 years, 71% of the Maintenance group had not had their disease return, while only 37% of the non-Maintenance group remained in remission.  

But it was Overall Survival that showed no difference. After 10 years, 83% of the Maintenance group was still alive, as was 84% of the non-Maintenance group. 

And the OS was what the researchers focused on. And of course, that's important. We all want to live longer. But I think the other numbers are important, too, and I have some thoughts about them.

This seems like a good time to remind you all that I am not an oncologist or a cancer researcher. The best person to talk to about treatment decisions is your own oncologist.

It seems to me that patients who receive only Rituxan are in a situation where they have a less aggressive version of FL. This was certainly the case for me. And while we do have some treatments that have the potential for very long-term remission, or even A Cure, we're not really there yet. So there may be some FL patients whose goal is to stay in remission for as long as possible. They know (or assume) that they will eventually need treatment again, and they want to delay it as long as possible. Maybe a Maintenance strategy is the best way to do that -- a relatively less aggressive treatment at first (compared to something like traditional chemo), followed by less aggressive treatments for a while. Of course, doing this also costs money, and increases the chance for infection, but also holds off more aggressive treatment for a while.

I'm not endorsing Rituxan Maintenance for anyone. I'm not endorsing any particular treatment at all. My point is not only that your oncologist is the best person to talk to about this, but also that your a very specific discussion of your goals should be a part of that conversation. Not everyone is looking for A Cure. Maybe your life style or your overall health make that difficult. But that's the ind of topic that should be a part of your oncologist visits. It is for mine. Even after 16 years, I want to know what the next steps might be, if I ever need them.

We are fortunate to have lots of choices. It's good to know what they are, and which is best for each of us.

 

16 Years

Today is my 16th diagnosiversary.

I was diagnosed with Follicular Lymphoma 16 years ago.

It has also been 14 years to the day that I started my first round of Rituxan.

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My diagnosiversary is always a day for reflection. It's actually more than just a day. It usually occurs to me sometime in October or November that The Day is coming up. That's when the reflection starts. I think back over the past year and what I've seen and done and been through. I think about what kind of lessons I've learned. Sometimes it's not so much about what I'm thinking. It's just what I'm feeling.

It has been a fairly eventful year. And high on the list of "events" was getting diagnosed with Basal Cell Carcinoma, a pretty common skin cancer, in October. As I wrote about when I got the diagnosis, it was not a surprise. I'd been having some Actinic Keratoses removed from my scalp and hands for the last few years (they are small benign growths that can lead to Squamous Cell Carcinoma if left untreated), so it always seemed like just a matter of time before one of those two types of skin cancer showed up. 

Being prepared for it emotionally was a good thing. I suppose I've been prepared for it emotionally for 16 years, in a way. Hearing a doctor say "You have cancer" is always awful -- the first, second, or tenth time. For me, the first time, with the Follicuar Lymphoma, was such a shock (I was 40 years old and in the best shape of my life at the time, something a lot of FL patients seem to say). That made it seem much worse. "You have cancer" is still not something I wanted to hear again, and I hope I never hear a third time. But there just seemed to be a kind of "Here we go again" feeling with the skin cancer diagnosis. I've done this before. I can handle it.  

So the day of the surgery wasn't as awful as it could have been. I had read the description of the procedure on the dermatologist's website and watched the videos that they recommended. I've been to enough appointments, had enough scans, and sat in enough treatment room chairs to know how to calm myself on an eventful day. As I was reading around on the dermatologist website, I read the "About" section of my surgeon (he is not my regular dermatologist). It said that one of his hobbies was collecting rare wines and whiskies. I can talk about whiskey all day. So on the day of the surgery, he gave me a local anesthetic, and he and I had a lovely conversation about Macallans and Springbanks while he did the surgery. 

It was an uneventful kind of eventful day. As a friend drove me home, I remember thinking "I get diagnosed with the most boring cancers." That's not a complaint.

But a few days later, I started thinking back on the surgery. I won't get into detail, because this is different than the Follicular Lymphoma experience that we all share. Let's just say I thought about all of the sensory details of the surgery -- the sights and smells and sounds and sensations. They were not pleasant memories.

It all reminded me at that point just how violent cancer can be. As a cancer patient, I've experienced plenty of small violences, with scalpels and needles and IVs and fingers and other things that have gone into me. That's all been a part of the cancer experience for even more than 16 years, since back before I even knew that I had cancer. But something about that moment of reflection a few days after the surgery just made it all new again. 

Cancer is a hard thing to escape. It stays with you. It's harder still when you have a cancer that is considered incurable, and one that makes you susceptible to secondary cancers. I've spent 16 years coming to peace with that. It was easier the second time. I was prepared.

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Another of the big events in this eventful year was going to Italy with my wife to celebrate our 30th anniversary. We actually just finished our scrap book from the trip about a week ago, many months later. It was nice to look back at all of the pictures we took, and some of the little souvenirs like ticket stubs that we'd saved, and to look at the diary that we kept during the trip. It was a high point of the year. Of the last few years, really.

It was paid for, in part, with some Cancer Money.

As I have discussed before, I don't monetize this blog. I don't have any advertisements on it, or charge anything for it. Some cancer bloggers do, and that's fine for them. I know some of them who can't work because of their health, and ad revenue is an important source of income. I'm fortunate that I am not in that situation. I'll remind you that, if you find a cancer resource online that you need to pay for, just make sure they provide sources for their information, and the sources are legitimate. Just linking to another blog is not legitimate, in my opinion. Make sure the information you pay for is good and trustworthy. 

So while I don't make money off of the blog directly, the blog has led to some really nice cancer-related opportunities that do pay me. Some of the writing I do elsewhere is for pay, though not all of it. I've done some small consulting jobs. Once I gave feedback to medical students learning how to deliver bad news. Another time, I was a judge for a contest. None of them pay a huge amount, usually enough for my wife and I to go out for a nice dinner (but not too nice). But it all adds up over time. We put that money in a special bank account. I call it "Cancer Money." My wife wishes I would call it something else. But it has a purpose -- to have some fun experiences.

Last year, we used some of the money to buy very overpriced tickets to see Bruce Springsteen. The concert was scheduled for March, but a week before the show, half of the E Street Band came down with Covid. They rescheduled for September. Two weeks before that show, Bruce was diagnosed with a very painful duodenal ulcer and he postponed again. So now we're rescheduled  for April -- we hope. 

Cancer Money is about finding the good in the bad. If cancer is going to take from me, I'm going to be darn sure to squeeze whatever I can from cancer. And I'm going to do something fun with it. It's easy to forget that, even with cancer, we're supposed to be having fun. It helps to be prepared for that, too.

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I don't know if any of you are Bruce Springsteen fans. I recommend one of his recent albums, Letter to You, which is a really wonderful meditation on the changes that come from getting older. Bruce is 74 years old, and he's still doing 3 hour shows when he's on tour. About 40 years ago, he decided that he was tired of being exhausted after his shows, and he started to pay more attention to his health. He prepared for the life he is still living now.

But he's also 74 years old. There are things that he can't control. Covid. Ulcers. Falling down during concerts every now and then. He's probably prepared for those things, too. He gets back up and plays on.

So if there's a lesson that I have learned over 16 years as a cancer patient, it's in those two stories, taken together. There needs to be a balance in our lives. As cancer patients, as much as we prepare ourselves for the bad things, we need to prepare for the good, too. We have to be emotionally ready for whatever difficulties that cancer brings us. But we need to be ready when the good opportunities happen -- emotionally, physically, even financially, as much as we are able. 

And then we need to be brave enough to take those good opportunities when they come.

Thank you, once again, for being such a big part of these 16 years. Stay well. And stay prepared. I hope a really good opportunity happens for you soon, and that you are prepared enough, and brave enough, to do it.\