ASH Reviews: MedPage Today on Follicular Lymphoma

Happy New Year!

I'm excited to be back for another year reading and writing about Follicular Lymphoma and other cancer-related topics. 

For the last few weeks, I've been looking at reviews of the presentations at the this year's ASH meeting. As I said a while ago, with a couple of exceptions, it seems like this year was about incremental progress. Lots of presentations on helping us understand certain treatments better, or improving current treatments in small ways. Which is great -- any forward progress is great.

This will probably be my last ASH review for the year; I'm getting lots of repeated information at this point. But what I'm offering is pretty nice -- MedPage Today's video series on Follicualr Lymphoma.

The series includes multiple videos featuring Lymphoma experts from The Ohio State University Wexner Medical Center. They look at a number of presentations from ASH related To FL (there are 10 videos in the series as I write this, with at least one more on the way). Some of them cover things that I have already written about, so I'm not going to mention them here -- you can watch the videos on your own.

But others are worth mentioning. The most recent video is called "AZD0486 Shows Good Efficacy in Relapsed/Refractory Follicular Lymphoma." It looks at the ASH Presentation #341 "Escalating Doses of AZD0486, a Novel CD19xCD3 T-Cell Engager, Result in High Complete Remissions with Rapid Clearance of Minimal Residual Disease in Patients with Relapsed/Refractory Follicular Lymphoma." It describes data from a phase 1 clinical trial for a new bispecific antbody. The results are good, with 47 patients in the trial, with about 62% of them not having disease progression within 24 months. The Overall Response Rate was 96% and the Complete Response Rate was 86%. The bispecific was designed in a way to attempt to minimize Cytokine Release Syndrome, and there were no serious CRS incidents, though there were other side effects, as expected. This was a small phase 1 trial, so there will need to be larger studies to confirm all of this good stuff.

The video series is heavy on bispecifics and CAR-T, which is not a surprise. As I have said many times before, those two types of treatments seem to create the most excitement among Lymphoma experts these days.

But there are others, including a video called "Pirtobrutinib Shows Potential in Heavily Pretreated Follicular Lymphoma." This looks at the ASH presentation #3026 "Pirtobrutinib, a Highly Selective, Non-Covalent (Reversible) BTK Inhibitor in Relapsed/Refractory Follicular Lymphoma: Results from the Phase 1/2 BRUIN Study."  

Pirtobrutinib is a BTK Inhibitor. Like all inhibitors, its job is to stop (or inhibit) some process that cancer cells need to happen in order for them to grow and stay alive. The best-known BTK inhibitor is Ibrutinib (notice how similar the name is to Pirtobrutinib), which has been very very successful in treating several B cell Lymphomas, but not in Follicular Lymphoma. So another attempt at a BTK inhibitor is welcome. This presentation looked at a phase 2 trial that had some success. The ORR was 50% , 14.6% Complete Responses and  35.4% Partial Responses, plus another 25% with stable disease.The panelists in the video were especially impressed with the safety profile. 

Finally, there is the video called "How Parsaclisib Compares to Other PI3K Inhibitors for Follicular Lymphoma." (This one features different experts that aren't from Ohio State.)  I found this one very interesting because it focuses on a PI3K Inhibitor. If you've been reading for a few years, you know my small obsession with PI3K inhibtiors. There were 4 of them approved by the FDA through accelerated approval, and none of them is available anymore. Two had safety issues and two had trouble getting patients into their phase 3 trials. So it's very interesting that another one is going through the pipeline, and the experts in the video talk about what might make this one different. (There is no link to the ASH presentation on the video age.) They agree that "we haven't moved past them yet," and the trick is to balance their effectiveness with the safety issues that came up. I don't know if this PI3K inhibitor will achieve that balance, but I have to say, I'm a little skeptical. I'd love to be wrong about this one.

So, as I said, this is probably my last ASH review until next December, unless something really interesting comes up. There's plenty more to write about already on my list, and no doubt lots more that I'm not even aware of yet.

Thanks for reading. I hope it's a great year for everyone.

Year-End Predictions

This is the last time I'll be posting in 2024. It's been an interesting year, for me personally and for the world of Follicular Lymphoma.

I had considered using this last post of the year to come up with a top 10 (or more likely a top 5) list of things that happened in 2024 related to FL. But honestly, I'm too busy and too tired, and even when I get a small break, something seems to fill my time. (Yesterday, it was our dog, who had to go to the hospital with an infection. She's doing fine. But my wife and I spent way more time than we wanted to trying to figure out how to get her to swallow her antibiotic pill. Our final solution involved American cheese, coconut milk-based yogurt, and cheese popcorn. But we got the job done.)

So instead of my going back and re-reading all of those posts and journal articles and figuring out how to rank them, I'm going to do something slightly different. I'm going to make three predictions about the long-term prospects of some of the FL-related things that happened this year. Maybe I'll remember to check in next year and see if I was right (though I think these might take more than a year to really work themselves out.

Prediction #1: Tafasitamab won't be the "game-changer" that the headlines predict it will. I've mentioned this a few times in the last month or so. The Big News fro the ASH meeting was the results of the stage 3 trial for Tafasitamab + Rituxan + Revlimd. Even before the ASH meeting, there were articles about how great the results were. And they were great. This is a non-chemo treatment with manageable side effects. It's been called a "game-changer." But to me, it's not going to change a lot of the ways that oncologists treat FL. As excited as many Lymphoma experts are about this, it matches the excitement that they had about R-Squared (Rituxan + Revlimid) a few years ago. But that doesn't mean that oncologists are recommending it. A survey by the Follicular Lymphoma Foundation found that only 6.2% of FL patients had received Revlimid (Lenalidomide), with or without Rituxan. I can't imagine that number is going to get bigger when a third agent is added to the mix. To be clear -- this combination is probably going to be approved by the end of 2025, and it's going to help a lot of people. But I predict that it won't be a game-changer. It won't become the default treatment for FL any time soon. Oncologists are creatures of habit. If you're seeing a generalist oncologist, get a second opinion from a Follicular Lymphoma expert if you can. See what other options are out there.

Prediction #2: Epcoritamab will have cause some concerns.  The ASH presentations for Epcoritamab, which was approved by the FDA this year, were very positive. It's the second bispecific approved by the FDA for FL. But the presentations also mentioned some safety issues. The same safety issues were voiced just after Epcoritamab data was presented at ASCO this year. The issues can be explained -- the clinical trial ran during the Covid pandemic, and like most FL treatments, Epcoritamab causes some immune system issues, which were especially important during Covid. Clearly, those issues were not enough to keep the FDA (or the EU) from approving it. But I have a feeling that there will be enough lingering concerns from oncologists that Epcoritamab won't be as widely used as it could be. I certainly hope that this isn't true, but my gut tells me those concerns haven't been completely answered. 

Prediction #3: There Won't Be Any Major Changes to the FDA Approval Process. This one is tricky. Back in March, I wrote about a movement to make the FDA cut back on surrogate endpoints and focus on Overall Survival. This would mean a longer, more rigorous approval process. However, in the second part of the year, political changes in the U.S. could potentially make it more likely that the FDA will loosen up regulations and be more friendly toward pharmaceutical companies, which  might make the process easier. Or maybe the opposite -- an FDA that does not have close relationships to people in the pharma industry. Honestly, I can't predict that, and we won't know what exactly will happen for another month at the earliest. But there is lots of speculation about potential good and bad changes at the agency and potential harm or help for cancer patients. My prediction? There will ultimately be little change. There might be a lot of big talk about change, but there will be very little actual change. Cancer treatments will remain safe and effective and will get approved only when they're ready. All of th talk won't match the reality.

So there you have it. My three FL predictions for 2025.

I want to remind you all that I am not an oncologist, or a cancer biologist, or a pharma insider, or anyone else that has any kind of information that would help with these predictions. Just a cancer patient who reads a lot. 

I hope you all have a Happy New Year. Eat your grapes, your black eyed peas, your soba noodles, your black bun, your crepes, and whatever else you eat to bring you good luck for the year. 

I'll be back soon with more. And you can all look forward to my diagnosiversary post in a coupe of weeks. I'll have some things to say.

 

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.