ASH Follow-Up: CAR-T and Bi-specifics for FL

I'm still seeing some analysis of what went on at this year's ASH conference. We're at the point where people are kind of taking a step back and thinking about what it all means.

One of those analyses that I found interesting was Dr. Toby Eyre from Oxford University Hospitals, who posted on Twitter with a nice chart comparing the two approved CAR-T treatments for Follicular Lymphoma with the bi-specific Mosunetuzumab, which in discussed in my last post.

[And before, I go further, thanks to Shelley for the link to the video of a lymphoma expert talking about his concerns with Mosunetuzumab. More on that in a second.]

 Dr. Eyre's chart compares some key features of Axi-Cel (the CAR-T treatment Yescarta), Tisagen (Tisagenlecleucel, another CAR-T also known as Kymriah), and Mosunetuzumab, the bi-specific.

 

 

The information on the left has more to do with the patients in the trial that he's reporting on. The info on the right is about the results -- Overall Response Rate and Complete Response Rate; estimated median PFS and Duration of Response; and then safety information (grade 3 and 4 infections; grade 1 and 2 Cytokine Release Syndrome; grade 3 and 4 CRS; grade 1 and 2 Immune effector Cell-Associated Neurotoxicity Syndrome, a measurement of side effects that damage nerves; and grade 3 and 4 ICANS). Grades 1 and 2 are less serious side effects than 3 and 4.  

It's interesting to see them all laid out next to each other, given that bi-specifics are often discussed as alternatives to CAR-T. Like CAR-T, bi-specifics activate T cells as a way of getting the immune system to react to the cancer cells. Unlike CAR-T, bi-specifics don't need to be made specially for each individual patient, so they'll be less expensive (at least in theory).

But they're not completely comparable, being different mechanisms. And, maybe more importantly, the two CAR-T treatments have already been approved, and have more data to look at than the bi-specific. It seems to me that they all have good and bad points to look at.

Now, back to the video that Shelley recommended, which you can watch here (it's actually a series of videos, so keep watching -- the bi-specific video is the second one). The specialist in the video, Dr. Noah Merin, points out that Mosunetuzumab activates T cells -- as I explained last time, that's what a bi-specific is. It's kind of two-sided with Rituxan on one end to grab onto the cancerous B cells, and on the other end, it grabs onto T cells. When the T cells are activated, the body has certain reactions, including a reaction that causes Cytokine Release Syndrome, or a "Cytokine Storm," where an over-active immune system can actually harm the patient. Dr. Merin compares it CAR-T, which also activates T cells and risks CRS. "It's CAR-T-like toxicities," he says. He thinks bi-specifics will ultimately not end up as a first treatment for FL, since the risk of CRS is so high. Instead, he thinks it will be used for patients whose disease isn't responding to Rituxan Maintenance (after immunochemotherapy, I assume) or isn't responding to R-Squared. So a 2nd or 3rd treatment, probably.

It's an interesting analysis. It also means that he thinks CAR-T probably isn't going to be a first-line treatment, either? That says something about CAR-T's potential as a "cure," at least as a first-line treatment.

It's hard to say what the Big Picture lesson is from all of this, other than to say that lots of Lymphoma specialists are very excited about the possibilities for al three of these treatments, while they also have some concerns about them.  My guess (and remember, this is the guess of someone who isn't a doctor) is that there will be a place for both CAR-T and bi-specifics for Follicular Lymphoma, and that doctors will continue to find ways to manage the side effects that come with both.

Good stuff.