What is Breyanzi or lisocabtagene maraleucel, and how does it treat CLL? Breyanzi is the brand name for listocabtagene maraleucel. Lisocabtagene maraleucel or liso-cel, all the same thing, is an anti Cd19 chimeric antigen receptor T cell therapy. Certainly a mouthful. We call them car T cell therapies. And how they work is they take your own T cells.

So you will get a blood draw called pheresis where they take out your blood, and then they take your own T cells, a specific type of white blood cell, genetically modify them and reinsert those T cells, which are now called car T cells. They refuse them back into you. So this is a new form of therapy, recently approved in 2017 for diffuse large B-cell lymphoma.

And now we have an approval for CLL. And so these car T cells are basically T cells that are manufactured to target your CLL. That anti Cd19 part of it that Cd19 lives on the outside of your CLL cells. And the car T cells now are able to attack the CLL. Who should consider receiving Breyanzi, and when is it typically used during CLL treatment?

There is a very specific subset of patients who benefit from car T cells at this point. Right now, the study that led to the approval of liso-cel was done in patients who have all received prior BTK inhibitors, including ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib, as well as prior Venetoclax therapy. So patients must have received all of our standard of care therapies first, having received two lines of therapy before they can get car T cell therapies.

So usually patients have exhausted all other treatment options before we're thinking about car T cell therapies. In addition, when they did the original study that led to the approval of liso-cel for patients with CLL, only a very small subset of patients actually found benefit with the drug. So in the original publications, they treated about 49 patients and only 21 patients actually responded to the drug.

And of those 21 patients, nine attained a complete response, which means they couldn't detect the CLL after therapy. In those nine patients, those nine patients did quite well, having prolonged survival benefit after receiving the liso-cel. But the 12 patients who had a partial response, meaning that we still could detect the CLL after treatment, many of those patients relapsed.

And so what I'm thinking about the patient who I'm thinking about car T cell therapy, they must have received all of our prior therapies. And we have a discussion about how I think that they will do with the car T cell therapy before we go forward with it. How is Car-T administered and what should patients know before receiving it?

Car T cell therapy is a little bit complicated in that we first apherese the patients meaning they come to our clinic and they have their blood drawn from them. And then that blood is sent out to be manufactured.

The time between the blood draw and actually getting the CAR-T cell therapy is usually around three weeks. Once the drug is manufactured to get shipped back to us and patients have to get chemotherapy. And what this chemotherapy does, and it’s only three days, is gets rid of all their current immune systems. Because we found that we want to get rid of their current immune system in order to make way for the T cells to be reinfused.

So they get chemotherapy for three days and then they get admitted typically. But sometimes this can be done as an outpatient to receive the car T cell therapy. The car T cell therapy then goes back into the patient via an infusion. And then they are monitored typically for around ten days in the hospital. But some institutes are starting to use this drug as an outpatient.

And they do require patients to come in daily for ten days after the car T cell therapy is infused. What side effects can CLL patients experience after receiving car T cell therapy? The reason why we have to monitor our patients very closely after infusing the car T cell product, and this is the same for CLL or other lymphomas, is because there is a high risk of toxicity.

The two main toxicities are called cytokine release syndrome and ICANS, otherwise known as neurotoxicity. So cytokine release syndrome is basically a situation where these car T cell therapies are working too well. They are basically using all their power to defeat the CLL to basically combat the CLL, or the other lymphoma. And this power leads to fevers, chills, basically inflamed situation.

And so we have to monitor patients closely for this cytokine release syndrome situation because patients can get really sick. It mimics a really bad infection can lead to hypotension. You might need ICU stay. And so this is the reason why we need to monitor patients so closely after Car T-cell infusion. The other toxicity, called ICANS or neurotoxicity, is in the name at least to neurologic situation, where basically patients can get really confused and can actually lead to seizures and a coma.

So once again, this is why we have to watch patients daily when we first infuse the car T cell therapy. That being said, even though we know these toxicities occur, they don't occur in everybody. Most patients will get some kind of cytokine release syndrome. About 80% of patients did have a cytokine release syndrome situation when they received car T cell therapy for their CLL, but it wasn't severe enough to require ICU stay.

Typically, it required some intervention like steroids, or another drug called tocilizumab. But the majority of patients did not require an ICU stay. But it can get severe. So that's why we have to monitor patients closely for it. The other side effects of CAR-T are more long term, and they can lead to increased rates of infection over the long term.

So we do encourage patients to have close follow up with their doctors over the long term as well. Are there any specific instructions CLL patients need to follow after receiving car T cell therapy? Normally, we require patients to stay within a certain amount of mileage or time from the hospital within the first 30 days of receiving car T cell therapy.

On June 27th, 2025, the FDA lifted the Rems requirements for Breyanzi. This changed the required length of time a patient should stay close to the hospital from four weeks to two weeks. If you'd like to learn more, read the article we've linked in the description. So talk to your doctor and find out what your institutions policies are. And once again, this is related to those toxicities the CRS and the neurotoxicity because we want you close to the hospital in case something were to happen.

So that way we can intervene as soon as possible. We also gave patients these little cards that tell them what they've received. So if they do wind up at a hospital that's not ours, they can show the card to the providers to let them know what's going on and how they can reach us, and to help best manage them if something were to happen.

How is the effectiveness of car T cell therapy determined? Normally, when patients get car T for CLL or other lymphomas, we do a CT scan at day 30. So 30 days post CAR-T, and then a pet CT at day 90. Some institutions do this a little bit differently, where they'll do a pet CT at day 30 and a CT scan at day 90, but you're going to have some kind of imaging at day 30 and day 90.

And we measure the effectiveness of the CAR-T cell therapy by using certain criteria called the IWCLL criteria. For lymphoma we use the Lugano criteria to help measure the effectiveness. And as we stated earlier, we know that patients who are able to get into a complete response, meaning that we're not able to detect the CLL, they do quite well after receiving car T cell therapy.

Can car T cell therapy cure CLL? car T cell therapy may be able to cure CLL. As stated, patients who get into a complete response with car T cell therapy have long term remissions, but we don't have long term follow up just yet. So the longest Follow-Up we have is currently around three years, and so hopefully with longer follow up, we'll find that some of those patients that are able to get into a complete response have long term resolution of their CLL, but time will tell.

We don't have enough data just yet. How does car T cell therapy compare to other CLL treatments like BTK inhibitors in terms of effectiveness and side effects? Currently, car T cell therapy is only approved after we've used our standard of care medications, and so it's really tough to compare the effectiveness of car T cell therapy versus other therapies for CLL.

I really think that there are two different pools of medications, because car T cell therapy is given only one time, whereas our other medications are given as either a time limited therapy over the course of a year or continuous therapy. And we're really reserving that car T cell therapy for patients who really exhausted all other options. And once again, the reason why we're doing that is because a car T cell therapy only works in a subset of patients and is associated with high toxicity, so we really only use it when we have to.

This might change as time goes on. There are new car T cell therapies that are being developed that appear to be more effective and have shorter manufacturing time, meaning that the time from taking your blood to making the product is shorter than the three weeks that we described. In addition, there's some news data that combines liso-cel, the car T cell therapy, with ibrutinib, our covalent BTK inihbitor that shows that when we use these two drugs combined together, the effectiveness is drastically increased.

Whereas liso-cel alone has been associated with a complete response of only about 20%. When we combine it with ibrutinib, that complete response rate increases to 40%. So we are finding new ways of causing the car T cell therapies to work better. And we're also having new car T cell therapies that are currently in development that appear to be potentially better with a more favorable side effect profile as well as a shorter manufacturing time.

What clinical trials are currently being done for car T cell therapy, and how might that affect patients in the future? There are a number of clinical trials that I'm aware of that are utilizing car T cell therapy for CLL, not just liso-cel. Two of the car T cell studies that I want to talk about. One combines the non-covalent BTK inhibitor nemtabrutinib with Car-T.

This is currently available in Seattle, and we're hoping that the combination of BTK inhibitors improves the efficacy of liso-cel. In addition, we have a trial here at Mount Sinai that's comparing or combining, I should say zanubrutinib with liso-cel for patients with Richter transformation. Richter transformation is when CLL turns into a diffuse large B-cell lymphoma. And we're hoping once again that the combination of a BTK inhibitor plus CAR-T cell therapy will lead to improvements in efficacy and safety than the Car-T itself alone.

In addition, we also have new car T's that are being studied that will hopefully improve on the efficacy of what we've already seen and also improved safety.

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