Sunday, April 14, 2024

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.

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