Peace

Today is Christmas Day, celebrated by may around the world, including many of you.

I like to use the day to think about Peace -- within each of us and all around us. 

Angels announcing the birth of Jesus included the phrase "Peace on Earth." This is, unfortunately, another year where there seems to be a lack of peace on earth. I won't bother listing the places where there are conflicts between nations. Or, in an even longer list, of conflicts within nations. I'm not sure which is worse. People who should be on the same side are listening more to the people who point out their differences than the people who point out their similarities.

I was thinking about a similar thing recently -- conflicts between people with Lymphoma. When I was first diagnosed, many years ago, I found an excellent online support group for patients with Non-Hodgkins Lymphoma. So there were folks with many different types (some researchers say there are as many as 70 different types of Lymphoma). Every now and then, there were be a little fight about who had it worse, people with Follicular Lymphoma or people with Diffuse Large B Cell Lymphoma, the two most common types of NHL. (This usually started when someone posted that they were told they had "the good kind of cancer," which is a silly thing to tell someone.) The DLBCL people would say the FL people had it better, since they had a slow-growing cancer that they could live with for years, maybe not even needing treatment. The FL people said the DLBCL people had it better, since their cancer could be treated and cured. 

The reality is this -- no cancer is "good," so no cancer is "better." Every cancer comes with a physical and emotional cost. They're all different, and they're all bad. And the best response to any of those comments about who had it better or worse is this: "We all have two things in common. We all heard someone tell is 'You have cancer,' and we all heard someone respond to out first post in the group with, 'Sorry you had to find us, but I'm glad you did'."

Our similarities matter much more than our differences. 

As I get older, I seem to see more and more people who are more concerned with differences. I think that comes from fear. The world is changing rapidly, and we want to hold on to the things we know and are comfortable with, even if they aren't good. That's only natural. 

But I think the antidote to that fear is in recognizing the similarities. Not everything has changed. Many things remain the same. There's peace to be found in that. 

And as I get older, that's the peace that I am looking for. Some inner peace amid all of the outer turmoil in the world.

So, as I often do on Christmas Day, I'm wishing you all some inner peace. At least for the day. Maybe for the rest of the year. Hopefully far beyond.

Stay well. Thanks for reading. 

 

ASH Review: MedScape on R/R FL

I'm still sifting through some of the commentaries that people are posting about what they saw and learned about Follicular Lymphoma at the ASH meeting. Today's commentary is a video, posted by the website MedScape, called "Charting New Horizons: Emerging Data and Novel Therapies in Relapsed/Refractory Follicular Lymphoma."

I guess it's technically a video, since it's posted on YouTube. But really, it's more like a podcast -- audio commentary without any real visual element. There is the option of seeing a transcript. You'll find a button in the description box below the video.

The post features two Lymphoma experts, Dr. Lori Sen from the University of British Columbia, and Dr. Cammy Maddox from Ohio State University. Their focus is on presentations from ASH that present data from studies on Relapsed and Refractory Follicular Lymphoma.

Of course, the first one they describe is the one that everyone is talking about: Tafasitamab and R-Squared. I've seen it called a "triumph" and a "practice-changer." Dr. Sen and Dr. Maddox seem equally impressed. They point out that the study was very wide, taking place in multiple countries. It was double-blind, meaning there was a direct comparison between two treatments. It had excellent results and good safety. And it showed that it is possible to combine two monoclonal antibodies -- one that targets CD 19 and one that targets CD20 -- and have good effectiveness and safety. I have to say, the more I read about it, the more impressed I am. I'm still not sure it will be the "game-changer" that some seem to think it will be. But that's  more about asking oncologists to break old habits than anything about how good the treatment is. 

The next presentation they describe is "337 Loncastuximab Tesirine with Rituximab Induces Robust and Durable Complete Metabolic Responses in High-Risk Relapsed/Refractory Follicular Lymphoma." Loncastuximab is an antibody conjugate. Basically, it's like Rituxan, targeting a protein on the surface of the lymphoma cell (CD19), but attached to it is a small drop of a chemotherapy drug. This allows the chemo to go directly to the cancer cell. In theory, this results in fewer side effects and better effectiveness. The Overall Response Rate was  97.1% after 12 weeks, with a Complete Response of 68.6%. For the FL patients in the study, the ORR was 100% and the Cr was 80%. Safety was good. A wider study is ongoing, so we may hear more about this one soon. 

The next presentation they look at is Epcoritimab with R-Squared, another one that has gotten lots of commentary since the meeting ended. I was curious about what they had to say about the possible safety issues with this treatment combination. They do mention that the study happened during the Covid pandemic, which likely affected things negatively (since the combination would affect immunity). There were no new side effects -- nothing unexpected. 

They finish by talking about how the data will affect clinical practice. Again, Tafasitamab and R-Squared have a prominent place here. In general, they seem to agree that the various presentations at ASH that excited them most are more proof that we are moving away from traditional chemotherapy and towards treatments that involve the immune system and that target lymphoma cells specifically. This has certainly been the trend for a while, and it's a good thing. They also agree that using these newer treatments effectively takes some learning on the part of oncologists. They will require active surveillance of side effects so things like Cytokine Release Syndrome don't become too dangerous.

It's an interesting video/audio, and it reaffirms a lot of what I've been reading and hearing so far.

Still a few more commentaries to sift through. If there's something good in them, I'll be sure to share.

ASH Review: 5 Year Follow-Up for CAR-T

Continuing our look at what Lymphoma experts have to say about presentations at ASH a couple of weeks ago. I'm seeing lots and lots of commentary about Tafasitamab + R-Squared (the excitement was there even before the ASH meeting began, so no surprise there).

One commetary caught my eye this morning. It's from the lead researcher for abstract #864, "5-Year Follow-up Analysis from ZUMA-5: A Phase 2 Trial of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma." 

The commentary is from an article website Health Day, and features a video (with written transcript) from a Leukemia specialist and a Lymphoma specialist.  The Lymphoma specialist is Dr. Sattva Neelapu from MD Anderson, who discusses the abstract above.

The presentation looks at data from the ZUMA-5 trial. There are a series of ZUMA trials, each looking at the CAR-T known as Axi-cel or Yescarta, but looking at the effects from different patient populations. ZUMA-5 focuses on patients with indolent NHL, including Follicular Lymphoma, who had relapsed or refractory disease. The ZUMA-5 trial actually resulted in Axi-cel being approved for R/R FL in 2021, so this research isn't about trying to show the FDA that it is safe and effective. We already knew that.

Instead, this presentation is meant to show that Axi-cel remains safe and effective. 

The study involved 159 patients, with 127 of them having been diagnosed with Follicular Lymphoma. The patients in the study had already received at least two other treatments, including immuno-chemotherapy (like R-CHOP or B-R). This presentation looks at what happened to the patients after 5 years. 

In the video, Dr. Neelapu says the Overall Response Rate was 90% and the Complete Response Rate was 75% -- even higher in patients with Follicular Lymphoma at 79%.

The median Duration of Response -- how long it kept the cancer away -- was a median of 60.4 months, or a little over 5 years. (Median means half had a longer response and half had a shorter response).

Among patients who achieved a CR, 58% remained in response after 5 years. The Progression Free Survival rate was similar at 50.4%. For patients with a Partial Response, the PFS was 6.9 months. The median Overall Survival was not reached. To get a median, you need half of the patients to have died, so after 5 years, more than half were still alive -- the researchers estimated 69% of the patients were still alive after 5 years.

Among patients with Follicualr Lymphoma, the OS was estimated at about 65%, meaning 35% of the patients had died, whether from disease progression or from some other cause. These other causes included some secondary cancers and infections, as well as non-cancer-related causes.

I their conclusion to the abstract, and in the video, the researchers say that the results show that Axi-cel may have the potential to be a cure for a certain subset of patients.

I have a couple of thoughts.

First, looking at the numbers, it's clear that CAR-T is improving. The early results from CAR-T showed that roughly 33% of patients had a long duration of response, 33% had a duration of about a year, and 33% did not respond at all. The numbers here after 5 years are a lot better. CAR-T is working, and after some time, oncologists are getting better at dealing with side effects and with identifying who will be helped by CAR-T. 

Second, that word "cure." It's a funny word when it comes to Follicular Lymphoma. Clearly, CAR-T was not a cure for a whole lot of patients in the study. But clearly, it has been a huge help to a whole lot of others. The problem with using that word is that "cure" is hard to measure. In other cancers, the 5 year mark is often used to declare someone as "cured." But FL has a habit of coming back even after 5 years, at least for some people. 

But many oncologists use the term "functional cure." If an FL patient is diagnosed at a later age and has a treatment that lasts for as long as they live, we can call that "cured." And for others, the disease may return, but in a less-aggressive way that doesn't require treatment. That makes them "cured," in a sense.

Many FL patients use the phrase "Dying with the disease, not from the disease." And that amounts to a "cure" in a way, too.

I have my own issues with the word "cure," obviously, and I may write more about that sometime soon. But for now, we at least agree that for many patients, Axi-cel CAR-T has been very successful.

I'm still sifting through some other post-ASH commentaries. I'll share more soon.

ASH Review: Epcoritimab + R-Squared

 OK, SH is over, and it's time to continue to look at some of the presentations that made some noise. We already looked at some of the FL presentations that got some attention (those presentations on diet and blood cancer had some people talking on Twitter/X). 

So now it's time to look at the presentations that are getting attention after the meeting is over. 

Let me first respond to a comment from a reader named Peter, who wrote about my post on the "triumph" of Tasafitamab. He wrote "I’m always a bit skeptical of headlines that use superlatives (like “triumph”), especially when they’re from less scientifically rigorous sources (like fiercepharma)....A good mantra I learned to repeat to myself, back when I was first getting diagnosed and learning about lymphoma, is “if something sounds too good to be true, it probably is”. I found it the best way to try to control my own confirmation bias."

Amen to that. And it is with Peter's words echoing that I present to you "342 Fixed-Duration Epcoritamab + R² Drives Deep and Durable Responses in Patients with Relapsed or Refractory Follicular Lymphoma: 2-Year Follow-up from Arm 2 of the Epcore NHL-2 Trial." 

This presentation looks at data from a phase 1b/2 clinical trial. (This means they have combined the phase 1 study, which focuses on safety, and the phase 2 study, which focuses on effectiveness -- they use many of the same patients rather than having to start a whole new trial). There were 111 patients in the trial, and they received the bispecific antibody Epcoritamab as well as the combination R-Squared (Rituxan + Revlimid, also known as Ledalidomide). The patients all had relapsed or refractory disease (their last treatment didn't work or had stopped working). 

The results were very good -- the patients had an Overall Response Rate of 96%, and a Complete Response Rate of 87%. That's pretty great. The treatment worked well no matter what the patients' treatment history was. Patients with POD24 had a CRR of 79%, for example. After a median follow up of 24 months, an estimated 69% of patients were still responding to the treatment, and 75% of those with a Complete Response had maintained their Complete Response.

The researchers note that the study took place during the Covid pandemic, and 57% of patients reported getting Covid at some point, resulting in a number of health problems, though there were no Covid-related decisions to stop Epcoritamab.  The most common side effects were were neutropenia (62%) and Cytokine Release Syndrome (51%). At a median of 25.3 months, 17 patients (15%) were still on the treatment; 41 patients (37%) had completed treatment as it was described in the study description; and 53 (48%) had stopped treatment for several reasons: 18 of them had their disease progress, 22 had severe side effects, 7 withdrew from the study on their own, 1 died, one left because of Covid, and 4 left becuase of a doctor's decision.

So why the "If it's too good to be true, it probably is" attitude? 

A lot of the post-meeting analysis will come in the next few weeks or months, at least from oncologists and oncology-focused web sites. The more immediate analysis come from other web sites, and that's where almost all of the news that I got about this presentation came from, namely, finance and investment web sites.

In other words, at least immediately after the ASH meeting, the folks who are most excited about this are the ones who will make some money off of it. 

I've struggled with this for years, and in the United States, we're in the middle of a very controversial situation that is related to it. I won't get into that, because I don't think I can describe my feelings about it very well. 

But I also have to have a little skepticism about the excitement that a new treatment regiment is generating based mostly on a press release from the company that has developed it. It might very well be one of the ASH presentations that oncologists are excited about, and that they'll discuss elsewhere. But I'm going to hold off on my excitement until then, especially given that almost half of the trial participants dropped out before they finished. In their abstract conclusion, the researchers point out that there are no new side effects, compared to the Epcoritamab trial that resulted in its being approved for FL by the FDA and the EU. (And despite there being some safety concerns about Epcoritamab, too.) A few people are talking about it online, but no one is really bursting with excitement.

The clinical trial had a few arms, so there were patients who received Epcoritamab and B-R, for example. It will be interesting to see what oncologists have to say about all of it in the next few weeks and months. I'll keep you posted.

In the meantime, be the good critical thinkers that you are. Stay hopeful, but realistic.

ASH Preview: Practice Changers?

The ASH conference is in full swing today, so I won't be calling my ASH posts "previews" after this. But I'll do it once more in looking at an article from Oncology News Central that was published earlier this week. 

It's really easy to get excited about a conference presentation, and even easier to get excited about an abstract. the presentation itself might last an hour, and involve more detail and some audience questions. the abstract is just the summary -- the good stuff. As Dr. Leonard points out in his Leonard List podcast, that can leave out a lot of the complications that can make it a little less exciting.

And then there's the place that a conference presentation has in the whole life cycle of a research project. The best look at research comes from a publication in a medical journal. That's where it will be peer-reviewed -- other experts in the subject will look it over and point out problems and ask for changes, and if it looks good after that, it will be published. A conference presentation doesn't go through all of that review.

My point is, remember that my ASH previews, that look at abstracts, are only the first step in a long process. The things I look at here -- and that I get excited about -- won't necessarily make their way to the doctor's office any time soon, if they do at all.

Which is why the article from Oncology News Central is so interesting. 

It asks the question, "What Blood Cancer Advances Could Change Practice?" In other words, which presentations at ASH really will end up in the doctor's office some day? They asked some blood cancer experts which abstracts could be important enough to change the way blood cancer patients are treated in the future.

Follicularr Lymphoma makes an appearance. they asked Dr. Cunthia Dunbar from the National Institues of Health, who also serves as Secretary of ASH. One of her picks is "LBA-1 Tafasitamab Plus Lenalidomide and Rituximab for Relapsed or Refractory Follicular Lymphoma: Results from a Phase 3 Study (inMIND)." It's the late-breaking abstract that I wrote about a couple of weeks ago, looking at Tafasitamab added to R Squared. As I said then, "I'm guessing this is going to be the Big Story about Follicular Lymphoma when the ASH conference is over, and we'll be hearing more excitement about it from the experts who give their opinions about things." So we're getting some of the excitement a little early.

Dr. Dunbar says “Tumor cells can evolve to escape targeted therapies via loss of a single target molecule, such as CD20. This approach of using two antibodies simultaneously aims to prevent this escape, resulting in better outcomes.”

That's the only abstract that deals directly with FL to make the list in this article. But there are a few others that get at Quality of Life issues that are worth looking at. The article has a section called "Diet and Lifestyle Focus “Bold and Different” From Previous ASH Meetings." A couple of abstracts look at the influence of higher fiber intake after Stem Cell Transplant, with the idea that they may improve gut bacteria in positive ways. Another looks at a ketogenic diet–derived metabolite that might have the potential to help CAR T be more effective.

I know there's a lot of interest among many FL patients for things like dietary changes that could help us. To be very clear, all of these studies are in very early stages. They are discussed in the article by Dr. Mikkael Sekeres of the University of Miami (a Lymphoma Rock Star, to be sure). But he cautions, "We need to wait for clinical trials before we recommend more restrictive diets whole hog."

You'll notice I have not linked to those studies directly. You can find links in the Oncology News Central article if you want to take a look.  But I'm going to make you work for it. Consider it symbolic -- we often look for quick answers when it comes to things like lifestyle changes to help our cancer.  But they're never that quick and easy. So if you want to read more about them, you'll need to work for it. 

And keep in mind that these abstracts aren't saying that a high fiber or keto diet will cure your cancer. They're looking at how dietary choices may influence how well a specific treatment works. that's a very different thing.

Still, I look forward to seeing the reactions to ASH. I'll share them as they come about over the next few days and weeks.