VIDEO: Deciding treatment plans for follicular lymphoma amid immunotherapy advancements

Editor’s note: This is a previously posted video, and the below is an automatically generated transcript to be used for informational purposes. Please notify editor@healio.com if there are concerns regarding accuracy of the transcription.

The Leukemia Lymphoma Society, they do team in training. And, I went out for one of their runs a couple of weeks ago, and a patient came up to me, they're training for the LA Marathon. So a patient came up to me and she said, I had CAR T in 2016, and she has no disease currently. So she got CAR T on a clinical trial at UCLA. And I said, how did it go? She said, well, I was in the ICU for a month, because she had a huge burden of disease going into it. So it's very high risk. She got significant cytokine release syndrome and neurotoxicity. Now four, five years later, it seems worth it. But, at the time, it's a very fraught decision about, do you want to undertake an extremely intense treatment after, maybe you've been already been treated for five years or 10 years? Are you gonna be fit? Are you gonna be able to withstand those toxicities, the risk of infection cytopenias? So, let's see. I think auto transplant follicular lymphoma is fading as a appealing strategy, because, if you're good enough to undergo auto transplant, then you probably would want to do CAR T. I mean, I think that's from a patient standpoint. The CAR T is potentially curative for follicular lymphoma. Whereas, autologous transplant is not considered curative. Most people are gonna relapse. I think auto transplant is not as appealing as CAR T in that space. But, on the other hand, in order to get CAR T you have to have measurable disease. So, if you're in a complete response, you're not eligible for CAR T. So you're in this situation where you have to kind of wait to progress or wait until your current therapy stopped working, or even come off maintenance rituximab in order to get some tumor appear on a PET/CT, so that you could then undergo CAR T. So that makes it a really complicated decision-making process with the patient. How much disease is worth it to undergo an intense therapy, with the knowledge that the more burden of disease you have, the higher risk CAR T is gonna be? The ideal patient has a few walnut sized tumors, but those are people that are not having a significant impact from their disease. And, I would say, that mirrors the situation with allogeneic transplant. Allogeneic transplant is surprisingly good for follicular lymphoma. You're talking about 70% cure rates. But most people don't do it. Most people don't want to do it. Most hematologists don't want to refer patients to have an allogeneic transplant for follicular lymphoma, because the same considerations that are present when you're evaluating somebody for CAR T, they apply even more so when you're talking about doing an allogeneic transplant. After allogeneic transplant, you have a risk of graft versus host disease. So you're asking patients to undergo a high intensity procedure, and then, there's a risk that they're gonna develop another disease that they are then gonna have, indefinitely, for the rest of their life, chronic GVHD. So, the chance of getting cured with allo transplant is probably, frankly, it's probably higher than getting cured with CAR T, but the risk of GVHD is a barrier to offering allogeneic transplant to more patients with follicular lymphoma. In the next few years, I would say, the science fiction approach is gonna be to make these decisions by using minimal residual disease testing, based on either sequencing the rearranged immunoglobulin heavy chain. You can do something called clonal sequencing, or clonoSEQ. And, you take a piece of the tumor, you sequence the specific B cell receptor that identifies the follicular lymphoma. And then, you can use that sequence to probe subsequent specimens to see if it's still there. So, you could do a blood test, and you could tell whether people have evidence of follicular lymphoma based on a blood test. You could have follicular lymphoma but render a negative test, because the sensitivity of the test is not known, especially for people that have low burden of disease. And the converse is also true, which is that, if you have measurable disease on a blood test, you don't know what the trajectory is gonna be. Is it gonna stay low level for 10 years and never be a problem? It's just a measurable signal in the blood, one cell in a million, but that doesn't ever turn into clinically observable, treatable disease. Or is it gonna be coming up quickly? And so, soon, the person is gonna have full blown relapse and need treatment. So, as we get more information about the performance of cell-free DNA tests or clonal sequencing for lymphoma, we'll have better understanding of whether we should use that information to tell people what treatment to get. Or if you have intended to be cured of therapy, if you have CAR T or if you have allogeneic transplant, and then it's there afterwards, does that mean you need to then do maintenance? Does that mean you need to follow up with additional treatment? I can envision a situation where a younger patient who's fit has CAR T and still has detectable, next generation-based sequencing clonal rearrangements, detectable in the blood after CAR T. Those patients might want to undergo allogeneic transplant. They might want to consolidate the CAR T remission, which may not be permanent, because you can still detect the disease post. It's somewhere. And you want to take that deep, deep remission and go directly into allogeneic transplant. That would be a very high intensity, potentially curative strategy that would be for a select subset of patients. The treatment side is getting more sophisticated, but the disease detection and monitoring side is also getting more sophisticated. We use that information to choose what treatment to offer to patients at different amount of disease, and, potentially, to tell who's cured from who isn't, much earlier than it would take for a tumor to grow back and show up on a PET/CT.