CAR-T Cell Therapy for Transformed Follicular Lymphoma | Matthew Cortese, MD | #ASH24

Hi, I'm Matt Cortese, I'm an assistant professor of oncology at Roswell Park Cancer Center in Buffalo, New York. I specialize in treating B-cell lymphomas and CLL. So in our study with 14 medical centers throughout the country, we were looking at outcomes of patients with transformed follicular lymphoma with something called chimeric antigen receptor T-cell therapy or Car-T. And Car-T is a way to treat cancers that have relapsed or have progressed despite conventional treatments, and uses our knowledge of the immune system to kill cancer directly. And this is a game changing and revolutionary new treatment approach, relatively new. And we were really trying to identify which subgroups of patients with lymphoma will do better, and who is not going to do so well so we can design better treatments, give patients the information they need hopefully in advance of going through treatments and help them with treatment selection and things like that are very, very important for us.

So we looked at transform Follicular Lymphoma, which is essentially a, aggressive change of a low grade lymphoma like follicular lymphoma. Follicular lymphoma is the most common indolent or slow growing lymphoma. And you know, despite that fact, you know, that slowly and typically doesn't cause problems for years. You know, we can safely watch folks for a long time.

Unfortunately, though, it can change, right? It can go and turn into a high grade B-cell lymphoma, similar to diffuse large B-cell lymphoma. And this happens randomly as of as far as we understand now. Where patients may feel well and these, aggressive lymphomas can emerge, and cause problems. We have to treat them urgently, immediately, just like we would with a more aggressive lymphoma, like large cell, Transform follicular lymphoma.

Is highly treatable, and the aggressive component is likely usually curable. Car-T cell therapy can cure folks who have relapsed despite multiple other treatments and, very, very effectively we've shown so in our it was a multicenter retrospective study, meaning we looked back in time and we see how people did, you know, after the fact.

And what we did was we looked at patients who have transform follicular lymphoma and compared them with regular diffuse large B-cell lymphoma. And we looked and saw how they how did people do with Car-T cell therapy and how long did they live? And we did a I think, a very robust analysis looking at, you know, survival outcomes.

And we've shown a massive benefit of Car-T cell therapy over de novo large cell lymphoma with Car-T, very statistically significant results. And this is actually a new finding for the field because we've known for a little while that transform lymphomas do better with Car-T cell therapy in our work with others, around the country at this meeting have shown that the transform follicular lymphoma component is actually responsible for the majority of that difference, and substantially better outcomes.

And we're going to have to look and see why that is. And, we've got some ideas on that, of course. So we know that, outcomes with Car-T cell therapy are improved if, if patients have little disease detectable at diagnosis, there's less toxicity, better efficacy. And there's, you know, so when I talk about toxicity with Car-T cell therapy, we're talking about inflammatory reactions, you know, infection risk, prolonged low cell counts after the fact.

So those are all certainly risks for everyone going through Car-T cell therapy, but they're less if you're less inflamed and you have less disease. And that's been shown with multiple studies around the country. And our study, will show similar findings as well.

So CRS or cytokine release syndrome is an inflammatory reaction. Personally I think it's a good thing to it's a low degree like less, low grade CRS is characterized by a fever. I usually, you know, try with Tylenol and close monitoring, usually an inpatient setting. There's outpatient Car-T cell therapy now, which is a wonderful thing for patients. But if people get a fever at home, we ask them to come in, because what can follow is low blood pressure, shortness of breath or ICANS which is a, neurotoxicity syndrome, which is associated with cellular therapies and bispecific therapies.

Where basically patients become confused, tired, highly treatable with steroids and other medications like Anakinra. And we get patients through those kinds of things really, really well. But it can be scary, certainly, as people are going through it.

So there are lots of factors that impact, survival outcomes with Car-T cell therapy. The most important one for me is can you survive treatment. Right. So how well are you able to get around the house, do your daily living. Are you physically strong enough to handle treatment? That's with any treatment. So good physical fitness, good nutrition, gentle exercise, pay attention to your body.

If something's wrong, see your doctor, ask questions, saying informed. Very, very important things to do. The other things that we looked at medically are how did you respond to the last treatment? So if you'd never gotten to a remission with, say, multiple lines of therapy, that tells you that your cancer is more aggressive, more resistant, and that can include Car-T cell therapy, but certainly Car-T can, potentially cure many, many patients who have these intrinsic resistance mechanisms baked in.

But not everyone. But just know that that can influence outcomes as well. Always stay posted, clinicaltrials.gov and you can search like you like you're shopping on Amazon and look through, available trials around the country. We've got many new Car-T trials out there. So even if patients relapse after CAR, We have bispecific antibodies approved. We have small molecules approved.

And then second and even third Car-T cell therapies are also are coming or active in trials, including at Roswell Park. So many, many good options out there.

This should give some reassurance to anyone with transformed Folllicular Lymphoma that your clinical outcome, your and your ability to survive treatments, and a long and healthy life hopefully is improved.

Actually your relative to, you know, regular diffuse large B-cell lymphoma, we've shown that your outcome actually might be much better than has been told to you originally, which is a good sign. That said, if you had another transformed lymphoma, we have some other data coming out, hopefully at the tandem meetings in February. But we're showing, you know, basically, similar results where other transform lymphomas behave more like regular large cell lymphoma.

And you may have less benefit, unfortunately, as opposed to the transform follicular lymphoma. We're doing translational work, now. And this is the most important thing in the future, number one, to make Car-T cell therapy safer, using small molecule inhibitors and other treatments to reduce the risk of toxicity, make T cells better. We had other work at this, presentation looking at things like Venetoclax for treating, you know, CLL, for example.

It's another topic for another day. But essentially we've shown that, that small molecule can improve immune function. And so this can be translated to patients with all kinds of other low grade lymphomas or high grade lymphomas, for that matter, to make toxicity much, much less. And, and hopefully, obviously work much, much better. So we get to 100% your rate over time.

It's going to take years to get there. But we're going to get there over in our lifetime, I think.