What are the types of CAR T-cell therapy products used in treating diffuse large B-cell lymphoma?

What are the types of CAR T-cell therapy products used in treating diffuse large B-cell lymphoma?

In the DLBCL space, we currently have three different types of CAR T-cells that are FDA approved and the FDA approved agents include axi-cel or Yescarta, liso-cel or Breyanzi, and tisa-cel or KYMRIAH. These are all approved for the third line setting in large cell lymphoma, but axi-cel and liso-cel are approved for the second line setting in the disease.

What is axicabtagene ciloleucel or Yescarta?

Axi-cel is the first product among all these CAR-T products that are now approved for large cell lymphoma that was first approved for the disease, the third line setting. Now it has second line approval as well. So this is a product that, what we call as a CD28 based CAR-T. So functionally it is slightly more rapidly expansive inside the patient's body. And some of the initial side effects that we experience after CAR-T cells are slightly more pronounced with this class of CAR-T cells. But this is a very effective product. And, that cell manufacturing is also much faster with this product compared to the other two. On an average, the cell turnaround is now between 14 to 17 days for the t-cells to come back to the patient site. So overall, we have axi-cel now approved in second line and third line setting. There are ongoing efforts to even in some institutions axi-cel can also be done as outpatient therapy. But here at our institution, we at least hospitalized the patients for a few days after axi-cel to monitor for any side effects.

What is lisocabtagene maraleucel or Breyanzi?

Liso-cel or Breyanzi is the second product that got approved for this disease. And it also has approval in the second line and third line setting. So liso-cel how it differs from axi-cel is that its costimulatory domain or one of the pieces of the CAR receptor is not CD28. But it's what we call as 4-1BB for this product. So it has a more gentler expansion and a smoother peak compared to the rapid peak with axi-cel in the patient. Turnaround time is slightly prolonged more around 3 to 4 weeks for this product, but much more safer, especially if you have a slightly more frailer elderly patient. Then we tend to prefer liso-cel over axi-cel. Again, there is no head to head comparison in a randomized fashion between these products. And so we can't really say one is superior to the other. Both are extremely effective. And both have both second and third line indications for large cell lymphoma.

What is tisagenlecleucel or Kymriah?

So tisa-cel is Kymriah, another 4-1BB-CAR-T. It was initially approved along with axi-cel for large B-cell lymphoma in the third line. But unfortunately for this product, in the second line study where that was compared against standard of care and bone marrow transplant, this product study did not meet the endpoint, so it still does not have a second line approval. So tisa-cel currently is more used for other lymphomas like follicular lymphoma and acute lymphoblastic leukemia. In the large B-cell lymphoma space, in the third line setting, it probably has a role, but tisa-cel is likely making a comeback with a more advanced version of itself, which is called as a rap-cel. And that possibly may become more standard of care very, very soon.

What do you need to know when deciding on a specific CAR T-cell therapy?

Between the three, I think at least one thing is clear for large B-cell lymphoma — axi-cel and liso-cel look to have a slight edge over tisa-cel, and that's been proven in the second line setting. Between product comparisons, as I said, in a randomized fashion, has not been conducted. Most of the data we have right now are like looking back in the real world and retrospective analysis, or comparing cross-trial comparisons, which are always not comparing oranges to oranges — you're doing apples to oranges comparison. But between axi-cel and liso-cel, for sure, they are very effective agents in the second and third line setting. And to choose between a product, a patient needs to know it all depends on what the treating facility is more accustomed to, which product can come back faster. If the patient, for example, has a lot of comorbidities like cardiac issues, lung issues, kidney or liver issues, we may tend towards liso-cel in such a patient because liso-cel also has an approval for that specific indication. For a patient who has a lot of comorbidities, liso-cel has an indication. So that's kind of the differentiator. And tisa-cel and liso-cel, we use it more for follicular lymphoma than large B-cell lymphoma.