I'm Back (from Italy)!

I've been reminding you that I'd be hard to get a hold of for a couple of weeks, but now I'm back. I was on vacation.

My wife and I spent 12 days in Italy.

We've been talking about doing this for 30 years, and a few years ago, we decided we would go there to celebrate our 30th anniversary, which was earlier this year. (Note that I was confident that I'd still be healthy enough to make the trip.) We went on a tour with Road Scholar (and if you're over 50, enjoy learning, and are hoping to travel abroad from the U.S., I highly recommend looking into what they offer). We went to Rome, Florence, and Venice. 

I can't really describe it all yet, but it included some wonderful experiences -- an after-hours, private tour of the Sistine Chapel; a tour of the olive oil production works (and a farm-to-table dinner) in Fiesole; a slow afternoon walk through the maze that is Venice; the many incredible works of art that fill Rome and Florence. Maybe just a few of the many pictures that we took will give you a sense of what we saw and did.

You know a trip was great when you're on the plane home and you're already planning the next one. We're still deciding where it will be. But there will be a next one.

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So what does this have to do with cancer? This is a cancer blog, after all.

There are two things.

I decided the first connection to cancer long before we ever made it to the airport. It's a lesson I hope we all already know. Cancer makes us prioritize. We need to do the things that we want to do. It took my wife and me 30 years to do it, but we did it. It's easy to want to pack as much into a life as possible, and easy to be disappointed if things don't happen immediately. But that doesn't mean they never will happen. Find the things you love and work toward them.

A few months ago, I saw a meme online. And while I don't think internet memes are meant to be a guide for life, this one hit me hard. It's a quote attributed to Buddha, but it was actually from a very modern book that was about Buddha. Yet the sentiment still stands:

"The trouble is, you think you have time."

Cancer patients probably know the truth of that more than most people. I've burned it into my brain. I knew it before this trip. But still, I want it to guide a lot of things I do.

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The second way this relates to cancer has to do with someone I met on the trip. Of course, she is a cancer patient.

The tour we went on included 16 other people. They were all amazing. Over 12 days, we had the chance to get to know each of them, hear their stories, hear their experiences. They were all the living embodiment of "The trouble is, you think you have time." 

As much as we tried to get to know everyone, we spent more time with one family than the others, a married couple and her mom. Wonderful people. And as we talked and shared our stories, it came out that the wife was a cancer patient, diagnosed with a form of lung cancer about two years ago. (I'm trying to respect her privacy, so I apologize if the lack of detail makes things a little harder to follow).

She and I have similar backgrounds, as far as work and education go. She's a writer and a Cancer Nerd, too. We traded blog addresses (she started one very soon after she got her possible diagnosis), and I read hers that night.

It always amazes me that our cancer stories are unique to us, but the details show how similar we are. She had gotten a Peloton bike just before she was diagnosed. As she was waiting for test results, she thought, "I can't have lung cancer. People who ride a Peloton can't have lung cancer." It reminded me so much of my own experience, running in 5k races, being in the best shape of my life, and thinking, "How can I possibly have cancer?" There were a bunch of those things in her blog, experiences that she wrote about that were so much a part of her own story, but at the same time so much a part of mine, and of all of our stories.

So here's this woman who has a story like mine, who lives clear across the country from me, and we had to travel to Europe to meet each other. (And in a weird coincidence, a couple of people that I love very much live within a half mile of her.)

I guess cancer has a way of connecting us. There are experiences we share that others just can't really understand, no matter how much they'd like to, and try to. And we somehow have a way of finding one another. 

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The ASCO conference started today, and I haven't looked at any of the information yet. I'll get there, and I'll write about what I see and read. Probably next week. Still enjoying that post-travel glow a little bit.

I wish you all good health, and the time to enjoy it.

Age, Stage, and Status in Predicting FL Survival

I want to share some research that was presented at the International Society for Pharmacoeconomics and Outcomes Research conference a couple of weeks ago. The research itself is interesting, but more importantly, it presents a chance to remind you about how to read statistics about cancer.

The presentation was called "Real-world Treatment Patterns and Survival Among Follicular Lymphoma Patients: A SEER-Medicare Analysis." Click here to see a copy of the poster that was presented. It looks at the kinds of treatments given to a large group of FL patients over 17 years, and also looks at survival statistics for the group.

The research uses data from a large database called SEER, or "Surveillance, Epidemiology, and End Results Program." This is basically a huge collection of medical records that keep track of the diagnosis, treatments, and outcomes of thousands of Follicular Lymphoma patients. This research looked at a particular group of patients -- those who were on Medicare (a U.S. government health insurance program for people at least 65 years old), and were diagnosed with Follicular Lymphoma between 2000 and 2017.

Two things are very important to keep in mind here.

First, these are patients on Medicare, so they are at least 65 years old. The median age for FL patients at diagnosis is somewhere in the 60s, so this group is basically the older half of the FL population. When you're looking at survival statistics, that's incredibly important. Survival statistics for younger patients will be higher -- generally, younger patients can handle more aggressive treatments, which usually result in longer times between treatments and better survival. And younger patients have a longer Overall Survival (that is, death by any cause) in general. So these statistics are for older FL patients, NOT for all FL patients.

Second, this research is describing patients who were diagnosed between 2000 and 2017. Now, 2017 is pretty recent, but even 6 years ago is a long time ago, in terms of treatments (think about the treatments that have been approved in the last 6 years -- they include bi-specifics and CAR-T, among others). So patients who were diagnosed 23 years ago had far, far fewer options than today. And those options were less targeted, so the long-term side effects of the patients in this study were likely much worse than we'd be dealing with today. That's going to have a big impact on survival statistics.

I'm telling you this (or reminding you about this) because I know from hard experience that looking at survival statistics can trigger some bad emotions. So I think it's important that you read statistics very carefully and not let the numbers overwhelm you.

Now, on to the research itself.

The researchers looked at the records of over 14,000 FL patients (a huge number). Because they were on Medicare, they were at least 65 years, with a median age of 76. Remember, in statistics, the median in the "middle number" of the group, so half of the patients in the study were between 65 and 76, and half were 76 or older. Again, the median is very important when looking at survival statistics. More on that below.

The researchers first looked at which treatments the patients received. For their first treatment, 60% of patients in the study received immunochemotherapy -- either Rituxan or Obinutuzumab plus chemotherapy (so something like R-CHOP or R-Bendamustine). Another 31% received just Rituxan or Obinituzumab, and 8.5% received chemo without the R or O. When it came to a second therapy (after the first one stopped working), only about 44% had immunochemotherapy. And about 42% had it for a third treatment.

Not surprisingly, there were NO patients who had CAR-T or an inhibitor for a first treatment. Fewer than 1% had one for a second treatment, and fewer than 2% had one for a third treatment. I say "not surprisingly" because this research goes back pretty far, looking at patients who were diagnosed before those newer treatments were available.

I will remind you again that age and year of diagnosis are so very important when reading these statistics. There just weren't the same options available 20 years ago. That's the main limitation of studies like this that look backwards.

Now, as far as survival goes, the researchers say that patients who received a first treatment had a median Overall Survival of 81.9 months. That is, they lived almost 7 years after their treatment. For patients who had a second treatment, the median OS was 49.6 months, or a little over 4 years. For patients who received a third treatment, the median OS was 35 months, or almost 3 years.

Looking at the age of patients, the median OS for patients diagnosed between 65 and 70 years old was 145.4 months, or about 12 years. For those 71 to 75 years old, the median OS was 110 months (about 9 years). For 76 to 80 years old, it was 81 months (almost 7 years). And for 81 and older, the median OS was 40.5 months, or about 3.5 years.

Here's where it's very important to pay close attention to how you read the statistics. 

First of all, remember what "median" means. It's the "middle number," so half of the people in the group will have a higher number for an Overall Survival and half will have a lower number.

Second, remember that these are statistics. They do not predict what will happen to any individual patient. The 65 year old patients in this study diagnosed with FL will, statistically, live for 12 years. But that means half will live less than 12 years, and half will live for more than that -- perhaps way more than that. Also, remember that OS doesn't measure death by cancer, but by ALL causes. So that group of 65 year olds will include someone who lived to be 100 years old AND someone who died from a hang-gliding accident the day after they turned 65. 

So this study is very interesting, but it as some real limitations. One of the biggest ones (and this is acknowledged by the researchers) is that these statistics don't include FL patients who were diagnosed before they turned 65. That's going to be about half of us, and I'm one of them. So for those of us in that group, don't pay attention to any of those survival statistics. They just don't apply to us.

As for those of you who were diagnosed after age 65, if you're worried about the survival statistics, remember what I said -- they don't say anything about your own individual situation.

But even looking at the median numbers, I think there is actually some very good news.

If we look at these age groups, and do some basic math, we get some interesting results. Accoridng to this study, an FL patient diagnosed at 70 has a median OS of 12 years. Statistically, they are likely to live until 82. A 75 year old patient has a median OS of 9 years, living statistically until 84. An 81 year old, statistically, lives until 84 as well.

So what is the life expectancy in the U.S. these days? About 76 years.

In other words, the median Overall Survival of the patients in this study is HIGHER than the life expectancy in the United States.

Now, life expectancy and survival statistics more complicated than what I am suggesting, and the complications aren't worth getting into. But to me, that just highlights even more the idea that it's just not worth worrying about statistics like these.

The most important lesson in all of this is that patients with Follicular Lymphoma can live long, happy lives, despite what statistics seem to say. It's better to not even pay attention to survival numbers. In the end, they don't really tell you much about your own life.

And let me be clear -- there's more to this study than I am talking about here. A lot more. Fr example, patients with comorbidities -- other serious health problems besides cancer -- have a lower Overall Survival.  So do patients who need multiple treatments. And so do patients with grade 3 disease. This study confirms those things, and those findings make sense. More aggressive cancers, and more health issues, cause more serious problems.

But when I read a study like this, that looks back at patients from 20+ years ago, I can't help but think about something I was told by Dr. C, the lymphoma specialist I saw when I was first diagnosed. He said, "Anything you read on the internet is already out of date."

In other words, there are many new treatments in development that haven't had their trial results published yet. And newer treatments like bi-specifics and CAR-Ts are extending Overall Survival so much that it can't even be measured yet -- so few patients in some studies have died that they can't come up with a median. And newer treatments are also giving us a better Quality of Life. I appreciate Dr. C's words every day.

And I think about something that another FL patients told me years ago. Their doctor said, "If we can keep a Follicular Lymphoma patient alive for 5 years, we can keep them alive for 50 years." Burn that one into your brain. We have options. We have hope -- and good reasons for that hope.

As always, thanks for reading.

I'm still unavailable for a few more days. I'll be back soon -- hopefully with some good news from ASCO.

Some Upcoming LRF Opportunities

As you probably know, I like to highlight some of the educational opportunities offered by LRF, the Lymphoma Research Foundation. I think the LRF does a great job with these. They have some excellent speakers -- experts who know the latest research, and know how to explain things to patients. 

You can find more information about LRF's upcoming opportunities by clicking here. There are both online webinars, and in-person workshops. (I think the in-person workshops are a fairly recent thing. Before the Covid pandemic, they were very popular. But then LRF went to only online for their events. Now they're back in person again, for some of them.)

One online opportunity that I think will be great is coming up very soon -- May 25 -- a webinar on Oral Therapies. The speakers will be Dr. Michael Williams from UVA Health and Dr. Deborah Stevens from the University of Utah. Oral Therapies are treatments that patients can take in pill form, usually once a day, rather than going into a clinic for an intravenous treatment. They include some of the PI3K inhibitors that ran into problems with the FDA, though there are a few others as well. The webinar will look at some new and upcoming oral therapies, and there will be a section on Quality of Life concerns. I'm especially pleased about the Q of L discussion. One of the common side effects from some oral therapies is increased digestion problems. I always like to hear experts talk about Quality of Life issues, so patients can make decisions on their own about whether the effectiveness is worth the possible lifestyle changes. This webinar is happening on May 25, so if you're interested, go to the LRF site for more information.

Another online event is happening on July 19. This one will be on Bispecifics. It should be great. As you probably know, bispecifics are one of the treatments (along with CAR-T) that get experts most excited these days.

Finally, there is one more webinar scheduled for July 25. This one is called "Lo Que Debe Saber Sobre El Linfoma" -- What You Should Know About Lymphoma. It will cover some basic information about lymphoma, and will be conducted in Spanish. That might be of interest to many of you. 

All of those will be online, so they are open to just about anyone.

As I said, LRF is going back to in-person events, too. One of these will be a day-long workshop in Chicago on June 17. Free breakfast and lunch! And some great information about Lymphoma, of course. More information here. 

Finally, the LRF has posted a "Save the Date" announcement for their annual North American Educational Forum, a 3 day event taking place October 6-8 in Brooklyn, New York. To be honest, I'm not sure how this is going to work. I've attended a couple of these in the last few years, when they have been online. So I'm not sure what kind of financial support there might be for people who want to travel there. I'm not too far from Brooklyn, so I'm giving some serious thought to attending this in person. If a bunch of you are planning to go, maybe we can plan a meet up. That would very cool. I'll post more details when the LRF makes them available. 

I hope one or more of these look interesting to you. As you now, I'm a big fan of staying informed, and the LRF does a great job with that.

(And a reminder -- I'm unavailable for a while longer, in case you're trying to get in touch with me. I'll be back soon.)

A Few Quick Updates

 A quick post today, with a few short items:

1) First, remember that there are only a few more days to endorse me (vote for me) for the Social Health Awards. I have been nominated for two awards, and we are coming to the end of the week-long endorsement/voting phase. After that period is over, some judges (made up of other health advocates) will also vote. The three nominees with the most endorsements/votes will be named finalists, along with the top three chosen by the advocate judges. (That's why being a finalist is so great. You get there either because your health community endorses you, or other advocates recognize your hard work and vote for you. Both are very cool things.) After that, a new panel of judges from the healthcare industry will decide the winners in each of the 10 categories. Winners will be announced in the summer.

You can find my profile here if you want to read more about me and/or endorse me. The last day to vote is Monday, May 21.

2) Second, following up on something I wrote last month, the FDA has approved Fast Track Designation for IMPT-314, the "bispecific CAR-T" treatment that binds to both the protein CD19 (like many CAR-Ts) and the protein CD20 (like many bispecifics). The designation is based on the results of a phase 1 trial involving 24 patients with aggressive lymphomas (including some aggressive Follicular Lymphomas). The results of the trial were impressive, with 91% of patients having a response, including 73% with Complete Response that lasted a median of 18.2 moths. Fast Track Designation from the FDA means the manufacturer has provided evidence that the new treatment will be effective and reasonably safe. The FDA will give extra feedback during the application process, and might approve it faster than it would otherwise, among other things. This will be an interesting one to watch over the next year or so.

3) Finally, over the next two weeks or so, I'm going to be much less available than usual. I probably won't be able to respond to emails or comments. There's nothing bad happening, and I'll tell you all about it when I can be available again. I'll try to write a couple of posts and have them scheduled to be published while I'm unavailable, so you won't miss me too much. Unfortunately, ASCO abstracts still haven't been released, so I won't be able to post anything about them. But there is some  good FL research I can share.

Thanks, as always, for your support. 

Vote for Me -- Social Health Awards

It's that time of year again -- the Social Health Awards!

Actually, it's about a month earlier than in the past, but still -- it's time for the Social Health Awards!

I'll start with a link. If you want to vote for me ("endorse" me, as it's called), you can find my Awards profile here. You don't need to "nominate" me (that's already been done). Look for the link that says "Endorse this Patient Leader." It looks like this:

Endorsements close soon -- Monday, May 22. So vote for/endorse me soon!

So now some background and reminders for how this works.

The Social Health Awards were created to recognize online health advocates (like me) who share their health story. This link will bring you the awards page, with lots of information about what they are and how they work. There are a bunch of different categories. As of this morning, I have been nominated for two of them: Creative Contributor and Revolutionary Researcher. Here's the description of the awards:

• Creative Contributor. There are so many avenues when it comes to patient advocacy. The Creative Contributor category recognizes the individuals taking a creative approach to raising awareness. Think about patient leaders transforming their advocacy into clothing, cards, jewelry shops, comic creation and more! This category celebrates those bringing advocacy to the marketplace.

• Revolutionary Researcher. The category aims to celebrate the patients and caregivers who refuse to let medical jargon and data slow them down! The winner of this category stays up-to-date on the latest research, treatments, and clinical trials. This patient leader has a knack for transforming complex information into layman terms for the greater community to act on.

One important thing about the awards, if you've never been involved with them -- you'll need to give them an email address (this is how they make sure that you don't vote more than once). If you'd rather not give out your email address, that's no problem -- no pressure to endorse me. I just want to make sure you know what you're getting into.

Endorsements end next Monday, May 22, so if you're interested in endorsing me, here's the link to my page again.

Thank you, as always, for reading the blog. 

Quick preview -- ASCO is happening soon. The conference organizers have once again generously made the online portions of the conference free for patient advocates, so I'll be reading up on all of that great research and offering some previews of presentations over the next few weeks. Always one of my favorite times of year.

Stay well, and thanks again for considering an endorsement.

CAR-T Approved in Europe (for Some Patients with FL)

The CAR-T treatment known as Liso-cel (Lisocabtagene Maraleucel) was approved by the European Commission last week for some patients with aggressive Follicular Lymphoma types. Liso-cel is also known as Breyanzi. This is the second version of CAR-T to get approval.

As a reminder: CAR-T (or Chimeric Antigen Receptor T-cell therapy) is the general name for a bunch of different treatments that work in the same way. In this treatment, a patient's T cells are removed (T cells are a kind of immune cell) and then changed in a laboratory so that they recognize cancer cells the same way they would recognize a virus or bacteria. Then they are put back into the patient, and they search for the cancer cells. It has been a very successful treatment for lots of blood cancer patients (though not all), and it's one of the treatments that oncologists get very excited about. However, it's also very expensive (it can cost almost US$500,000), and some patients can have severe side effects.

The EC approval is for aggressive lymphomas, including Grade 3b Follicular Lymphoma grade 3B (FL3B), who relapsed within 12 months of receiving immuno-chemotherapy, or who are refractory to it (it didn't work when they tried it).

The approval comes from the results of a phase 3 clinical trial called TRANSFORM. The patients in the study were put into two groups. the first received "standard of care" (that is, what they would have received if they weren't in a trial) -- immuno-chemotherapy, and a stem cell transplant if that didn't work. The other group received chemotherapy and then the CAR-T.

The results were what we have come to expect at this point, with the CAR-T group having a 73.9% Complete Response, versus 43.5% for the chemo group. The chemo group's median Progression Free Survival was 6.2 months, while the CAR-T group's median was not yet reached after 17.5 months (in other words, more than half of the group was still responding after almost a year and a half).

And side effects were manageable for the CAR-T group, with Cytokine Release Syndrome and nerve-related side effects both common, but taken care of quickly (as CAR-T becomes more common, doctors are much more aware of these side effects and take care of them before they become too problematic).

While this affects a small subset of patients with FL, it's another step toward having this CAR-T approved for other patients with Follicular Lymphoma. (In fact, the day before this news was announced, the makers of Breyanzi announced positive results for a phase 2 trial involving Relapsed/Refractory FL patients.)

It's all very good news, and just more evidence that CAR-T is likely to be a part of many more FL patients' futures.

Subcutaneous Rituxan for FL

Interesting research in The Journal of Clinical Oncology on how Rituxan is delivered to Follicular Lymphoma patients with low tumor burden. I think it has the potential to change how patients get Rituxan. As someone who was in this exact situation, I find it particularly interesting.

The article is called "Randomized Phase III Trial Evaluating Subcutaneous Rituximab for the First-Line Treatment of Low–Tumor Burden Follicular Lymphoma: Results of a LYSA Study," and as the title says, it reports on the results of a phase III clinical trial.

A little background first. Some FL patients are able to have just Rituxan as a first treatment. Typically, this happens with patients with a fairly slow-growing type of FL with low tumor burden. 

What exactly is "low tumor burden"? It took me much longer to find an answer than it probably should have, but this write up for a clinical trial from 2004 defines it this way:

• Must meet the following criteria for low tumor burden:

  • No nodal or extranodal mass at least 7 cm
  • Less than 3 nodal masses greater than 3 cm in diameter
  • No systemic symptoms or B symptoms
  • No splenomegaly greater than 16 cm by a computed tomography (CT) scan
  • No evidence of risk of compression of a vital organ (i.e., ureteral or epidural)
  • No leukemic phase with greater than 5,000/mm^3 circulating lymphocytes

  • No cytopenias, defined as any of the following:

    • Platelet count less than 100,000/mm^3
    • Hemoglobin less than 10 g/dL
    • Absolute neutrophil count less than 1,500/mm^3

 To put it simply, the affected lymph nodes need to be a certain small size, there can't be too many of them, blood counts have to be close to normal, and the nodes can't be affecting any vital organs. When I was diagnosed, I was low tumor burden. Two years later, some nodes had grown big enough that they were blocking something and making my leg swell up. Time for Rituxan!

So for the phase III trial described in this article, a group of 202 FL patients were divided randomly into two groups. The first group received intravenous Rituxan, once a week for four weeks, intravenously, with a line into the arm or hand.  This is usually the way patients receive Rituxan, and it was the way I received it (except I had it for 6 weeks instead of 4).

The second group had one round of intravenous Rituxan, but then had four more weekly rounds of subcutaneous Rituxan (a shot from a needle, rather than a line going into the arm). Subcutaneous Rituxan usually goes in faster, so it saves time and money for everyone. In addition to these four rounds, this second group also had subcutaneous Rituxan Maintenance -- four more rounds, every two months. That's a little different than Rituxan Maintenance usually works. It's usually every two months for two full years.

So the study wanted to find out more about two things -- first, is the Subcutaneous Rituxan more effective than the Intravenous Rituxan? And second, is this shorter Maintenance schedule better than the usual longer one?

It's kind of a funny study, because it's not really comparing two of the same things. The Maintenance adds some extra treatment that makes it hard to compare IV and SC Rituxan. It's not comparing apples to apples. It's more like apples to apple pie with ice cream.

And the researchers know that and acknowledge it.

The study's main way of measuring was Progression Free Survival -- how long it took for the disease to come back.  The 4-year PFS was 58.1% for the Subcutaneous group, and 41,2% for the IV group. 

The Complete Response Rate was higher for the Subcutaneous group (59%) than the IV group (36.6%). But there were no differences in the Time to Next Treatment or Overall Survival.  

In conclusion, the researchers found that it wasn't the Subcutaneous delivery that resulted in better outcomes, but in getting more Rituxan early on.

And that makes sense.  More treatment = more results.

What's important here, in the end, is that is shows that Rituxan Maintenance can be helpful without stretching it out for two years. One of the problems with such long Maintenance is that the treatment lowers immunity, since it wipes out B cells. Doing that for 4 weeks is OK, but doing it for 2 years could result in some immunity problems and make the patient more vulnerable to infections. A shorter time might be a batter balance of good results with good safety.

However, the researchers also point to some limitations. It is possible, for example, that a higher dose of Rituxan right away will be more effective (since Subcutaneous Rituxan allows for a higher dose). It's also possible that the "maintenance" isn't necessary, and just stretching out the dosing to three months might be more effective than 4 weeks (the good results came in the first three months, not in month 5, 7, or 9).

So, in the end, the study probably raises more questions than it answers. And that's OK. A someone who benefited from Rituxan only as a treatment, I'd love to be able to see more people have it, and avoid more aggressive treatments if they can. And if a study like this helps us rethink something so successful, then I'm all for it.

More research to come soon. Thanks for reading.