Great article a couple of weeks ago from the journal Blood Advances, which is published by the folks at ASH. The article is called "The rules of T-cell engagement: Current state of CAR T cells and bispecific antibodies in B-cell lymphomas."
This isn't giving a description of original research. It's one of those "Here's where we stand today" articles that sums up everything that's happening with a topic. In this case, it's looking at two types of treatments, CAR-T and bispecific antibodies.
If you've been a regular reader lately, you know that, at least in my view, the these are the two treatment types that get lymphoma oncologists/hematologists most excited. They have been around for a few years, so their effectiveness is pretty well-known. And there is more and more research happening to improve them in different ways, whether by finding new targets for them or reducing their side effects.
A quick reminder: CAR-T stands for Chimeric Antigen Receptor–modified T cells. CAR-T works by removing some of a patient's T cells (a type of immune cell) and changing them in a laboratory so they more easily recognize cancer cells. Then they are put back into the body and allowed to do their job. It's been a very successful treatment for many (though not all) patients. CAR-T can have some severe side effects, though as CAR-T is used more, oncologists are getting better at identifying them and trying to manage them.
Bispecifics are different. They are made up of two parts (that's why they are called "bi," meaning "two." One part seeks out a protein found on the surface of a B cell, similar to what Rituxan does. But the other part seeks out a protein on a T cell (there's that immune cell again). By bringing the T cell next to the cancer cell, it allows the T cell to eliminate it. This also can have some serious side effects, and has also been very successful for many (but not all) patients.
The article provides some of this background, but also looks specifically at which CAR-T and bispecific treatments have been approved for use with certain types of lymphoma. Of course, Follicular Lymphoma is one of those types, which is why I'm writing about it.
As the chart from the article shows, there are three CAR-T treatments approved for FL (at least in the U.S.) -- known as Axi-cel, Tisa-cel, and Liso-cel. And there are two bispecifics currently approved -- Mosunetuzumab and Epcoritamab. The chart shows which line of treatment they have been approved for (it's third line or later for all five of them, at least for now), gives some data about effectiveness (the Overall and Complete Response Rates), and some information about safety (the percentage of patients who experienced particular side effects).
It's a really nice chart (if you're into that kind of thing. And I am.)
There's also a bit of a longer discussion for each of the different types of lymphoma, and the section on FL is very interesting.
The authors talk a little bit about sequencing of treatments. For advanced or bulky disease, they usually go with immuno-chemotherapy (something like R-CHOP or B-R, I assume), if that seems appropriate for the patient. They typically go for R-squared (Lenalidomide + Rituxan) for a second treatment. And then they express their happiness that CAR-T and bispecifics are now available for a third line, which have greatly increased the options that patients have.
I appreciate their careful discussion of third-line treatment decisions. As they say, neither CAR-T nor bispecifics are shown to cure FL, so patient choice becomes very important. And there are lots of factors to consider, from cost (CAR-T is much higher) to side effects and quality of life. They also mention that younger patients might prefer CAR-T, since there is a greater chance of it being a "one and done" treatment. Patients who have transformed might also prefer CAR-T, since it is very effective against transformed FL.
Finally, the article describes some of the current and future research happening with CAR-T and bispecifics. This includes using either of them in combination with other treatments, using bispecifics after CAR-T as a type of maintenance, and using either of them as a first or second line treatment.
As I said, it's a good article in that it brings a lot of stuff together in one place, and it's clear why these two are so exciting. I don't have a sense of whether there are other types of lymphoma treatments being developed that also use T cells to go after B lymphocytes, but my guess is that with the success of these two treatments, there are plenty of ambitious and innovative researchers who are looking.
The bottom line is, once again, that we have options, and there are more coming. That should make us all a little bit happier.
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