Tuesday, June 4, 2024

ASCO: Bispecifics for Follicular Lymphoma

As I have said, there isn't too much new and exciting related to Follicular Lymphoma at ASCO this year. One big theme, though -- Lymphoma experts are still very excited about bispecific antibodies.

In case you need a reminder, bispecifics work a lot like the monoclonal antibodies that have been around for almost 30 years. A monoclonal antibody (like Rituxan) works by attaching itself to a protein on the cancer cell (Rituxan attaches to the CD20 protein, like many bispecifics). What makes a bispecific different is that it also attaches to a protein (like CD3) on a T cell, a kind of immune cell. By bringing the cancer cell next to the immune cell, the bispecific uses the body's own immune system to treat the cancer.

Trials treating FL with bispecifics have been very successful, with one already approved and a number of  others at different stages of the trial and approval process. (Search for bispecifics in this blog and you'll see what I mean.)

A large percentage of the FL presentations at ASCO are about bispecifics. It's one of the two treatment types (along with CAR-T) that get talked about most by lymphoma experts these days.

So I was excited to see that there was a session on Bispecifics at ASCO -- not presenting trial results, but an hour-long discussion with a panel of experts. It's called "Innovative Strategies: Bispecific Antibodies for Relapsed/Refractory Follicular Lymphoma," and you can watch it on YouTube with the link in the title.

It's worth the hour it takes to watch it. You'll get a good sense of the state of the art with bispecifics. I will caution, though, that in this video, the cameras stay on the three doctors. They keep referring to slides with data and information, but they don't show them in this recording. But that's OK -- you miss out on some specifics, but you get the sense of what's happening. They're excited -- that much is obvious.

I won't summarize the entire hour discussion, but I do want to share some important highlights. 

The three presnters are Dr. Gilles Salles of Sloan Kettering in New York, Dr. Joshua Brody of Mount Sinai in New York, and Dr. Matt Lunning of the University of Nebraska.

Before they got into their individual presentations, they did some polling of the oncologists in the audience. They first asked them what their experience is with bispecifics. Again, I can't see the actual results, but they do discuss them. About half of the oncologists there had no experience at all with bispecifics. Another big chunk had only used them once or twice.The conference is a mix of researchers and clinical oncologists (the folks you see in their offices), so this makes sense. Bispecifics are pretty new, and the one approval is for Relapsed/Refractory FL, so that narrows the number of patients who even have the chance to see them. 

But it also makes the point that I need to hear. As much as I read about bispecifics when I do research on FL, a lot of that is in the lab, not the clinic. In other words, what we're seeing at ASCO, with most FL presentations being about bispecifics, that doesn't mean they are showing up in the oncologists offices.

That said, one of the panelists also warned the clinical oncologists in the audience to learn all that they could, because bispecifics are going to be an important part of treatment plans for FL in the very near future.

Along those same lines -- another poll asked the audience members how many bispecifics had actually been approved. We know the answer is just one (so far) but a lot of the audience got it wrong and thought there were more that have been approved. That's understandable -- many oncologists are generalists that treat many different kinds of cancer. But it again reinforces the idea that bispecifics are probbaly talked about and written about more than they are actually used at this point.

A lot of the discussion from here was providing some important clinical information and advice, particularly related to side effects and how to identify and treat them before they become problematic. CRS (Cytokine Release Syndrome) is an issue for bispecifics, and the panel offered advice on how to deal with it. (And they make the point that it is less common to have serious CRS with bispecifics than with CAR-T, but it's still important to keep an eye on it.)

As for the future of bispecifics, as I said, they warn the members of the audience to learn what they can, because they are likely to become a more important part of treatment regiments very soon. The panelists were asked what kind of advice they would give to clinical oncologists about using bispecifics. One pointed out how important it is to follow dosing instructions to prevent CRS. The other suggested they keep in touch with researchers who have used bispecifics a lot in clinical trials, and who continue to use them, because we are learning more and more about them all of the time. Once again, these answers point to how little experience most oncologists have with them. 

In another response, one of the panelists said that it was very possible that bispecifics would be used the way Rituxan is used now. It is used and it works, and then perhaps the FL returns, so bispecifics are used again, and again if necessary, until they stop working. That says a lot about how these experts think about bispecifics effectiveness but also their safety. 

As I said there is much more here. I've tried to share what I think are the highlights. 

I think the takeaways here are 1) lymphoma experts continue to be excited about bispecifics; 2) data continues to come in that justifies that excitement; 3) it's pretty likely that your oncologist hasn't used bispecifics, especially if you are not seeing one in a research hospital; and 4) it's pretty likely that bispecifics are going to be a part of many FL patients' treatment plan at some point in the future, as a first line treatment and for R/R patients.

I'll keep digging into the FL information that's being presented at the conference and report what I find out. Not as rich a mine to explore as in the past, but some good nuggets in there.


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