CAR-T Treatment Options for R/R DLBCL

Ian W. Flinn, MD, PhD: Kami, there are now 2 FDA-approved products for relapsed large B-cell lymphoma, and there’s another 1 that’s going through the process, hopefully to get approved. The trials are different, in regard to how patients went on them, but there are some very real differences in the constructs of these therapies. Do you think they’re different? Do you use different therapies for different patients? Will you use one CAR T-cell therapy for 1 patient vs another? Can you discuss some of the differences and similarities among these?

Kami J. Maddocks, MD: Yes. The general structure is similar. They differ in their combinations of the transmembrane and costimulatory domain. All 3 are a bit different in that regard. When you look at the trial populations, they all included relapsed/refractory diffuse large B-cell transformed lymphoma, high-grade lymphoma. Axi-cel [axicabtagene ciloleucel] also included primary mediastinal patients, as I believe Amit Mehta mentioned. Liso-cel [lisocabtagene maraleucel] included primary mediastinal patients and grade 3B follicular lymphoma patients.

The axi-cel trial did not allow bridging therapy, whereas the tisa-cel [tisagenlecleucel] and liso-cel [lisocabtagene maraleucel] trials did allow bridging therapy. So there’s a little bit of a difference there.

Of the 2 approved products, axi-cel [axicabtagene ciloleucel] is typically given as an inpatient therapy, whereas tisa-cel [tisagenlecleucel] can be given as an outpatient therapy.

In regard to the liso-cel [lisocabtagene maraleucel] product, when you look at the general patient population they didn’t seem to treat as robust of a patient population. Almost 40% or a little higher of the population was over age 65, whereas with the other 2, about a quarter of patients were over age 65. So it’s an older population. The cutoffs for both, as Loretta mentioned, from renal function and cardiac function were lower than in the other trials. There were differences in the patient populations, as you mentioned.

Only axi-cel [axicabtagene ciloleucel] and tisa-cel [tisagenlecleucel] are approved. At our institution, it seems that we tend to use it in the older population.

Ian W. Flinn, MD, PhD: Are you standardly using just 1, or do you use both?

Kami J. Maddocks, MD: We use both of the approved products.

Ian W. Flinn, MD, PhD: OK. We’re going to get Loretta’s take on the real-world data in a second, but do you think the CD28 construct has a different adverse-event profile compared with a 4-1BB product, or are those just the differences we’re seeing in the trial—different time, different patient population—and maybe that explains it? What is your experience treating people with a commercial product off-trial?

Kami J. Maddocks, MD: It varies. Based on the patient population and the patient you’re treating, there’s probably a difference. There’s some difference in the product but also the patient’s disease status and underlying comorbidities, at least from what we’ve seen.

Ian W. Flinn, MD, PhD: The major question that comes up a lot, at least in the marketing wars between trying to differentiate 1 from another: Does persistence matter? What’s your take on this? Some of them have a different area under the curve, for lack of a better term. Do you think that is a difference, or are the results the results, and it doesn’t really matter how you got them?

Kami J. Maddocks, MD: I think there is some benefit to the persistence.

Transcript Edited for Clarity