Promising Results for CAR-T Cell therapy for Follicular Lymphoma | Matthew Frank, MD, PhD | #ASH24

Nice to meet you. So my name is Matthew Frank, I’m a lymphoma specialist at Stanford. I work on Car-T cell therapies for patients with lymphoma, including Follicular lymphoma and mantle cell lymphoma. So for the first time, we're presenting a new clinical trial that's investigating a novel CD 22, directed Car-T cell therapy. So CD 22 is a protein found on cancer cells found on follicular lymphoma and mantle cell.

And, car therapy is an immune based therapy where we genetically modify a patient's immune cells to attack and clear their cancer. So this is a brand new trial, but it, was inspired by a prior trial that we've completed in a different lymphoma called diffuse large B-cell lymphoma, where this therapy worked very well for patients who have already had a prior car and then progressed anyway.

And we've now treated seven patients, and we're delighted to see that all seven have responded. So CAR-19 therapy is, now FDA approved for patients with many types of lymphoma, including large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. I'm grateful to have that therapy, in some cases to provide these very durable remissions. We'd like to say the word cure, but we never know until patients have lived long enough.

But, very promising, durable remissions for patients who've, been through a number of other lines of therapy, including chemotherapy and other therapies. But when a patient's already had that therapy, we worry that another car therapy won't work as well. But we're delighted to see is it actually does it actually works quite well in large B-cell lymphoma.

So the difference here is that it's going after a different target on the cancer. So instead of Cd19, that protein, it's going after CD22, a different protein. So we're measuring some important things like can we make it because this is the first time we're making it for this, these indications. And so far we've made, the product successfully every time.

But one and that one case, we were able to collect cells from that patient again. And we were successful the second round of manufacturing. We're also measuring, how much trouble does it cause a patient? We don't want this to be too toxic. And I'm delighted to say you don't see any neurotoxicity, which is very common with, CD 19 cars.

We do see cytokine release syndrome, a flu like illness, but it's not required any ICU care. It's been mostly just fevers and and, well, manageable. So we measure toxicity, and then we, of course, what patients want to know is, does it work. So there's key metrics like overall response rate complete response rate. So a complete response is when we go looking for it on a scan or blood test, we don't see it.

And then there's a number of secondary or correlative metrics looking at why it works or how it works or why doesn't it work. And so those are looking at things like how much of the CD22 protein is on the cancer, and does that matter for response. What does the Car T-cell phenotype meaning what kind of T cells are there because there's different types of T cells.

And does that pattern matter? And some other, metrics of just how well does it work? So how effective is this CD22 car for patients with follicular lymphoma and mantle cell lymphoma? So it's still early days. So, so we just opened a trial about six months ago. So we we don't have a lot of a long term follow up.

We only have two patients with follicular lymphoma that are out six months. But what I can tell you is all four patients with follicular lymphoma have had a complete response. Maybe we look for the cancer. We don't see it. And then in mantle cell, we've had, two out of three have a complete response and one have a partial response.

So it's been a great start so far. And these have been in high risk patients are patients who, either have had a prior Cd19 car or in follicular lymphoma, patients who progressed within two years of their initial therapy are considered higher risk. And we've had two patients like that who've also had a complete response. So delighted to see that these very high risk patients are responding as well as they are.

So this therapy in large B-cell lymphoma, we ran a trial, and the data looked promising enough to the, FDA that there's a special designation called Breakthrough designation. It essentially says that this is, a promising emerging therapy that has the potential to meet a big unmet need. So for comparison, I'll say that this therapy was given to patients who had about a five and a half to six months predicted survival.

And when we gave it, that predicted survival moved out to about 25 months. So a major improvement. And really what ended up happening is some patients appear to be cured and other patients who didn't have a durable remission, unfortunately didn't do as well. But because of how safe it was and because of how effective it was, the FDA agreed that this needs to have special designation to help it move through the approval process faster.

So seven patients to start with is great, but we really want to enroll, up to 30 plus patients in both follicular lymphoma and an additional 30 plus patients in mantle cell lymphoma. It's important to test it across a lot of different patients because we get a better sense. Every patient's unique. We want to see how it works through lots of different folks.

So that's really the next step is just to continue to enroll patients over the next couple of years. And if it looks promising enough, then it warrants a larger what's called phase two trial, where it's not run at just at Stanford, where we're running this trial, but run across the U.S. or the world to see how it works in the hands of lots of different investigators.

A more real world sort of experience. So, finish up this trial, move on to the phase two trial. So this is, it's always important for patients to realize that this is a phase one trial, but there's no placebo here, so this is a real therapy. We're using a dose that we think is a very good optimal dose.

If they're interested in the trial, they can reach out to us. And we're happy to talk with them and their physicians. There's lots of effective therapies. And we're just happy to add yet probably one more promising option for everybody.