Real-World Use of CAR T-Cell Therapy in Relapsed/Refractory DLBCL

Transcript:

Matthew A. Lunning, DO, FACP: I'm going to stick with you and I'm going to ask about disease burden. I think we all struggle with this as we try to translate the clinical trial data into the real-world experience about not giving chemotherapy just to give chemotherapy while the disease is worsening. How do we control the burden of the disease and how does burden of disease impact outcome of CAR T cell?

Jason Westin, MD, MS, FACP: Disease burden is a big deal both in terms of how we view which therapy to give which patient, but also in terms of what their experience might be when they received the treatment for the original ZUMA-1 (NCT02348216) clinical trial, there was data presented at an ASCO 2020—somewhere in there; a few years ago—meeting showing that patients with the highest quartile disease burden had the worst outcomes with chemotherapy. Effectively, the more aggressive and more bulky the disease, the harder it was to control. It's hard to know if that's a surrogate for disease biology patients who have a high disease burden that's not by chance; that's because they have some ultra-aggressive version of lymphoma. Nonetheless, having a high disease burden is consistent with bad outcomes, probably not limited only to CAR T-cell therapy, but sure, that's true for axi-cel. It also correlates to higher rates of toxicity. That's something to consider. In terms of, would you do anything to wait for CAR T cell to try and debunk the patient? That's unknown. Bridging therapy, generally for CAR T cell associated with worse outcome—again, that might be a chicken and egg thing about who gets bridging therapy—it's the person with rapidly progressing disease. Surprise, rapidly growing cancer is worse than not rapidly growing cancer. I personally don't use bridging therapy as a debunk the patient first strategy, I try to get to a CAR T cell as quickly as I can, but for that patient who's rapidly progressing, often they will have bulky disease. They probably will benefit from something to hold their disease back while you're waiting for the CAR T cell.

Matthew A. Lunning, DO, FACP: We talk about taking the ZUMA-7 (NCT03391466) data, which we've had at our hands for several months now. We now have the overall survival advantage. We still live outside of clinical trials and an intent to CAR environment, where clinical trials didn’t, they started the clock at consent or at apheresis, but we live in the real world. What percentage of your patients do you want to do CAR T cell in, do you actually get to infusion of the CAR T cell taken into fact that there's some logistical barriers that was commented on that may rise up or insurance issues before apheresis or even apheresis in itself. What's your number that you think is your true intent to CAR, get to CAR, percentage?

Jason Westin, MD, MS, FACP: It's a moving target. I'd say that when CAR T cells were first approved 5, 6 years ago, that number was not as high as we wanted it to be. We had a lot of barriers in terms of payers, who would ask, “what is a CAR T cell?” when you’d call and ask to get an approval. In my practice nowadays, most payers know what CAR T cells are, they know the indications, and our team has a relatively streamlined approach for that request to go in for the approval to come back and then apheresis to be scheduled. There still are bottlenecks in terms of getting the apheresis slot for some of the CAR T cell products. Sometimes apheresis slots are too far away, and that's a problem that we need to keep working on to increase capacity. More importantly for your question is the folks who never come see me for CAR T cell: the patients who live in a rural community or are elderly or don't have the logistical or financial support to pick up and effectively stay at a CAR T cell center for a month or 2, that's a big barrier. There's a large portion of patients with large–cell lymphoma who are CAR eligible, but they aren’t seen at a CAR T cell center for those reasons.

Matthew A. Lunning, DO, FACP: So, they're never counted in the true denominator there. Dr Flinn, what you heard at ASCO 2023 this year about ZUMA-7 with the overall survival advantage? Has it changed your perception on CAR T cell in the second line? Or is it the same and you thought this was going to come out but didn't know?

Ian W. Flinn, MD, PhD: I was optimistic that we would ultimately see an overall survival and accepted that, but it's good to see in print, and that reinforces our approach in second-line therapy for patients with large–cell lymphoma.

Matthew A. Lunning, DO, FACP: Dr Rhodes, we've heard about axi-cel in the second line and liso-cell in the second line, what's a CAR T cell eligible patient or what's even a CAR T cell ineligible patient? How do you tease out who those patients are that are walking into your clinic?

Joanna M. Rhodes, MD, MSCE: That's a great question. Now with the liso-cel approval, I think that there are very few patients [who] are truly CAR T ineligible.

Matthew A. Lunning, DO, FACP: You mean age isn't a defined CAR T cell eligibility?

Joanna M. Rhodes, MD, MSCE: I do not think that age is a defining characteristic of who is a CAR T candidate. To me, my gestalt on it is do I think they could survive an ICU stay.

Matthew A. Lunning, DO, FACP: Why are they in the ICU?

Joanna M. Rhodes, MD, MSCE: While we've gotten much better at managing ICANS and CRS, things still happen. That's my weird benchmark of trying to figure out if I think you can survive an ICU stay, it probably means that you are hardy enough to be able to get therapy and do well with it. We never want to do is do CAR T cells on patients that aren't able to tolerate that. Now, what that looks like, I think it ends up being very frail patients that are walking in, perhaps that are patients that aren't particularly mobile, are probably the ones that are more likely to be CAR T ineligible. That's my quick and dirty method of trying to discern who's who.

Matthew A. Lunning, DO, FACP: Dr Westin, what do you think about CAR T cell eligible versus not eligible?

Jason Westin, MD, MS, FACP: I agree with Dr Rhodes, it's difficult to define; it's a little bit of the eyeball test, but we do like to have some objective metrics that we can put on things. In several of the publications, looking at patients in the real world who got CAR T cell, a few things shook out that correlated with bad outcomes and that namely, as Dr Rhodes mentioned, is being ambulatory. Part of that goes into performance status, so patients that have a poor performance status, 2, 3, 4, more so the 3 and the 4s, are going to have a hard time and have worse outcomes.There are exceptions to the rule of everybody could be eligible for CAR, but I think the data we're hearing about in the second line effectively is changing the paradigm where we no longer ask, are you transplant eligible? Which is a different version of the question you asked or transplant ineligible. Now it's how long from therapy are you? And in that early relapse population, I agree, I think most patients are going to be eligible for CAR T-cell therapy.

Transcript edited for clarity.