The Expanding Role of CAR T Cells in Lymphoma and Leukemia - Episode 10

LBCL Therapy: The Right Therapy

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Stephen J. Schuster, MD: This is a great question that was posed. I don’t know the answer to it, but I’d certainly love to hear the opinions on it. We know there are 2 efficacious agents out there. And we know that there’s 1 coming. Let’s assume it’s here. How are you going to choose? Matt?

Matthew J. Frigault, MD: I’m of the mindset that depending on the logistics and the circumstances, it’s down to certain strategies. The CIBMTR [Center for International Blood and Marrow Transplant Research] registry data that were presented at ASH [the American Society of Hematology annual meeting] this past year did touch on this little bit, where you tended to have younger patients who didn’t have as many comorbidities getting access. All this is center-specific, because I know some people look at it as getting the sicker patients to an infusion as quickly as possible. [Tisagenlecleucel] patients tended to be a little bit sicker. They tended to have more morbidities, more cardiac disease, more involvement with secondary CNS [central nervous system] lymphoma. That’s one component. We’ve got to analyze the liso-cel [lisocabtagene maraleucel] data once they are available and reviewable. That’s where the registries become important to be able to compare. But ultimately, it comes down to optimizing the patient.

For us, at least how I approach it is, for the double-hits primary refractories, regardless of age, are pretty much going to something like axi-cel [axicabtagene ciloleucel], because you need fast, reliable manufacturing that’s going to get back to you quickly. And also [tisagenlecleucel], for those patients who tend to be a bit older, who are a little bit frailer, for whom neurotoxicity means 4 weeks in a rehab facility tied to a bed, I’m not sure that’s in their best interest.

Matthew J. Frigault, MD: As we were discussing how we’re getting better, the 2 drugs that we’re talking about for managing the toxicities are toci [tocilizumab] and steroids. And we’ve been talking about these same drugs for a very long time. As we start understanding mechanisms of toxicity and employing other agents, it’s going to get better and potentially allow sicker patients, or patients we previously wouldn’t treat, or change the paradigm for how we’re doing product selection. Efficacy is ultimately a product of overall response rates, but also the patients surviving the treatment that you’re giving.

David Miklos, MD: There was a quote that’s become my most famous line, that “we treat them all because that’s what the patient needs.” And it’s not right to withhold a therapy that’s so effective. But price and opportunity for especially those patients on Medicare has been a big driver, and no matter what anybody says, has been impacting how patients get their therapy. The recent announcement from our administration that they’re seeking the…really big DRG [diagnosis-related group] is great news for the patients to remove price from how we’re managing their care. And I’d like to see therapies in the outpatient setting as well. But some of the therapies are just requiring inpatient toxicity management.

Caron Jacobson, MD: There are 2 ways that a patient can be sicker. They can be sicker from their lymphoma, and they can be sicker from other medical problems. And so I think it depends how they’re sicker that will pick the product that they’re going to use at this point.

Stephen J. Schuster, MD: If they’re sick enough, either way, they end up in the hospital. But I’ll tell you that external factors other than money, believe it or not, sometimes influence choices. Early in the COVID-19 [coronavirus disease 2019] epidemic, when we were expecting to have inadequate numbers of beds, we started using tisagenlecleucel almost exclusively because we didn’t want to commit patients to even a 10-day hospital stay or a 7-day hospital stay. But unfortunately, as it materialized, the peak of COVID-19 in Philadelphia was not so great, and we ended up having a surplus of beds and space. But not every city had the same experience. I think every now and then, you don’t have a choice.

Matthew J. Frigault, MD: Also with [tisagenlecleucel], sometimes you can use a cryopreserved product. And in some circumstances, having the ability to cryopreserve opens other doors in terms of bridging therapies or logistical circumstances that the patients are dealing with. It’s not just the efficacy reporting from the clinical trials. It’s how you get them there.

Stephen J. Schuster, MD: It’s interesting, and correct me if I’m wrong, but in Europe, [axicabtagene ciloleucel] can be made from cryopreserved cells.

Matthew J. Frigault, MD: How cohort 4 of the early steroid use was done is every patient was cryopreserved and then manufactured…I believe.

Stephen J. Schuster, MD: Well, I’m hoping that that crosses back over the Atlantic to us, the ability to cryopreserve, regardless of product. That being said, Matt, what I think is that the reason you need a higher lymphocyte count for [tisagenlecleucel] is because you do cryopreserve and thaw, and you lose cells that way. And so there is some rationale for shipping a fresh product.

Matthew J. Frigault, MD: Yes.

Stephen J. Schuster, MD: Low counts. And that goes the same with [lisocabtagene maraleucel] as well, where we ship fresh products. They can almost produce lymphocytes out of thin air, in my experience. It’s because you’re sending them a fresh product. It makes a huge difference.

Matthew J. Frigault, MD: But even for products that, for failed manufacturing runs from a fresh product, there’s usually a frozen backup that can also be used. They do have a good success rate with that.

Stephen J. Schuster, MD: In patients we were treating with [axicabtagene ciloleucel], they went to the backup product and did it. In fact, we were impressed by that enough, that anybody that we get more than enough cells for at Penn [Abramson Cancer Center], we freeze cells and keep them at our institution as backup. I don’t know how long that’ll last, but at least it’s what we’ve been doing.

Transcript Edited for Clarity