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Is the Community Setting Ready for CAR T-Cell Therapy?

Panelists: David Maloney, MD, PhD, Fred Hutchinson Cancer Research Center; Nilanjan Ghosh, MD, PhD, Levine Cancer Institute/Atrium Health; Leo I. Gordon, MD, FACP, Robert H. Lurie Comprehensive Cancer Center; Matthew Lunning, DO, University of Nebraska Medical Center; Michael Pulsipher, MD Children
Published: Wednesday, Jan 30, 2019



Transcript: 

David Maloney, MD, PhD: What about moving this into a community setting? What do you guys think?

Leo I. Gordon, MD, FACP: I think that’s an important question. It’s been raised by the commercial arms of all of the companies doing this, these studies, because it will be open to more patients. I think you have to start with centers that have a transplant program. I would say that as a bare minimum, partly because the requirement is that these be FACT [Foundation for the Accreditation of Cellular Therapy] accredited anyway, and so I think you have to have a transplant program.

I would be cautious about this until we’ve got more data on managing toxicity. I don’t think it’s ready for that yet, but down the road I think as we learn more about it and how to manage the toxicities better, it theoretically could be done.

Michael Pulsipher, MD: I think in a community setting what you really need is a setup that can handle it. In other words, in many community practices the physicians, the oncologists, are doing a variety of things and they’re not always accessible. You have to be on the spot, you have to be intensely managing CAR T-cell–type approach. But I certainly could envision a community setting, say, where they have a focused leukemia team or lymphoma team, where they have inpatient people who are on the floor all the time and can manage it, where they have an ICU [intensive care unit] that’s been trained. So in that very specific setting.

Leo I. Gordon, MD, FACP: Narrow.

Michael Pulsipher, MD: Yes, but you’re either all in or not for CAR T cells.

Leo I. Gordon, MD, FACP: Right.

David Maloney, MD, PhD: But nobody’s mentioned that this is complicated. I guess we have, but it’s complicated, and you can’t just get approved to do this just because you want to, right? There’s this REMS [Risk Evaluation and Mitigation Strategies] program, which is quite difficult, and there’s also the FACT accreditation, which seems to be increasingly for immune effector cells, which is increasingly being applied. I’m sure you guys are all dealing with all of this as well.

Michael Pulsipher, MD: Yes, we’re already fully FACT accredited for effector cells. But that’s expensive. It takes a huge regulatory apparatus in order to keep it up. You have to have quality that goes on and on. You have to have a very good apheresis team. You have to have a stem cell processing laboratory. So it’s not trivial.

David Maloney, MD, PhD: At our institution I think we had to train 300 and something people—not patients, people—to be able to actually give these 2 commercially approved drugs.

Matthew Lunning, DO: Right. I don’t know the number off of my head, but I’m just thinking about 1 patient going from the consultation through CAR T cell. The number of resources and employees for that 1 patient to make that one CAR T-cell therapy happen, in my mind, equates to 20 discrete jobs that they will do to get that patient from the consultation through the CAR T cell. It’s a major deal.

Nilanjan Ghosh, MD, PhD: So is it easier or harder than running a transplant center?

David Maloney, MD, PhD: It’s a really good question, and I think it’s going to depend on the CAR. Because right now even grade 2 cytokine release syndrome [CRS] is tough to manage. Patients are getting tocilizumab, and so do you foresee managing CRS or neurologic toxicity as an outpatient? I don’t see that happening.

Nilanjan Ghosh, MD, PhD: I think the important message, again, is taking the ZUMA-1 data, if neurotoxicity—even early grade neurotoxicity and CRS—is in the order of 60% to 90%, the deaths were only 3. So this means that intervention really helped to convert those into manageable things where patients don’t have to die and could ultimately benefit. We see now in the real-world experience from the 2 abstracts presented with about 400 patient data that the use of tocilizumab and steroids has been more common. And that, at least I know in a nonrandomized fashion, did not seem to have an effect on efficacy. So people are trying to use these agents early on, but they have to be comfortable in identifying them early on at the first headache or the slight change in mental status, the multiple neurotoxicity checks. With slight hypotension, if you miss that, then you’re dealing with grade 3. So if you are not in a setting where you can pick these things up early and intervene early, then you’re going to have to deal with a lot of difficult toxicities. And we did see that quick translation, and I’m sure this usage is just going to go up, and people need to be comfortable and in many places have doses of tocilizumab available before you give CAR therapy.

Michael Pulsipher, MD: Well you can’t get past the REMS program unless you have it available.

Nilanjan Ghosh, MD, PhD: Right, so those are things that are very important.

Matthew Lunning, DO: I think you hit it correctly, and you said “early.” But there’s a difference between that and prophylactic. And I think there’s a small experience with the axi-cel [axicabtagene ciloleucel] and early prophylactic tocilizumab use that may predict for more high-grade neurotoxicity. So early, yes; prophylactic, no.

Michael Pulsipher, MD: I think we need to be careful with these algorithms. If we give it too soon we may kill effector with that. And so if we’re going to be changing the algorithms very dramatically, we’ve got to study it, we’ve got to have a specific study.

David Maloney, MD, PhD: But this does lead to a lot of problems because if we actually look at the REMS programs, they’re different for each of these products. In fact, they’re telling you to do exactly different things at different times. And I think that what we’re seeing now in the real-world experience is that they’re converging more towards an earlier adoption of intervention to keep people out of the ICU, but this is going to require some further education.

Matthew Lunning, DO: Yes, if you get 3 constructs on the same floor, you almost need to have blue shirts, red shirts, green shirts.

Michael Pulsipher, MD: We have, because with the studies it’s equally an issue. You’re supposed to manage it according to what your study says. We have different outlines for each study and it’s a challenge.

Nilanjan Ghosh, MD, PhD: And then you add multiple diseases. Just imagine the complexities.

Transcript Edited for Clarity 

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Transcript: 

David Maloney, MD, PhD: What about moving this into a community setting? What do you guys think?

Leo I. Gordon, MD, FACP: I think that’s an important question. It’s been raised by the commercial arms of all of the companies doing this, these studies, because it will be open to more patients. I think you have to start with centers that have a transplant program. I would say that as a bare minimum, partly because the requirement is that these be FACT [Foundation for the Accreditation of Cellular Therapy] accredited anyway, and so I think you have to have a transplant program.

I would be cautious about this until we’ve got more data on managing toxicity. I don’t think it’s ready for that yet, but down the road I think as we learn more about it and how to manage the toxicities better, it theoretically could be done.

Michael Pulsipher, MD: I think in a community setting what you really need is a setup that can handle it. In other words, in many community practices the physicians, the oncologists, are doing a variety of things and they’re not always accessible. You have to be on the spot, you have to be intensely managing CAR T-cell–type approach. But I certainly could envision a community setting, say, where they have a focused leukemia team or lymphoma team, where they have inpatient people who are on the floor all the time and can manage it, where they have an ICU [intensive care unit] that’s been trained. So in that very specific setting.

Leo I. Gordon, MD, FACP: Narrow.

Michael Pulsipher, MD: Yes, but you’re either all in or not for CAR T cells.

Leo I. Gordon, MD, FACP: Right.

David Maloney, MD, PhD: But nobody’s mentioned that this is complicated. I guess we have, but it’s complicated, and you can’t just get approved to do this just because you want to, right? There’s this REMS [Risk Evaluation and Mitigation Strategies] program, which is quite difficult, and there’s also the FACT accreditation, which seems to be increasingly for immune effector cells, which is increasingly being applied. I’m sure you guys are all dealing with all of this as well.

Michael Pulsipher, MD: Yes, we’re already fully FACT accredited for effector cells. But that’s expensive. It takes a huge regulatory apparatus in order to keep it up. You have to have quality that goes on and on. You have to have a very good apheresis team. You have to have a stem cell processing laboratory. So it’s not trivial.

David Maloney, MD, PhD: At our institution I think we had to train 300 and something people—not patients, people—to be able to actually give these 2 commercially approved drugs.

Matthew Lunning, DO: Right. I don’t know the number off of my head, but I’m just thinking about 1 patient going from the consultation through CAR T cell. The number of resources and employees for that 1 patient to make that one CAR T-cell therapy happen, in my mind, equates to 20 discrete jobs that they will do to get that patient from the consultation through the CAR T cell. It’s a major deal.

Nilanjan Ghosh, MD, PhD: So is it easier or harder than running a transplant center?

David Maloney, MD, PhD: It’s a really good question, and I think it’s going to depend on the CAR. Because right now even grade 2 cytokine release syndrome [CRS] is tough to manage. Patients are getting tocilizumab, and so do you foresee managing CRS or neurologic toxicity as an outpatient? I don’t see that happening.

Nilanjan Ghosh, MD, PhD: I think the important message, again, is taking the ZUMA-1 data, if neurotoxicity—even early grade neurotoxicity and CRS—is in the order of 60% to 90%, the deaths were only 3. So this means that intervention really helped to convert those into manageable things where patients don’t have to die and could ultimately benefit. We see now in the real-world experience from the 2 abstracts presented with about 400 patient data that the use of tocilizumab and steroids has been more common. And that, at least I know in a nonrandomized fashion, did not seem to have an effect on efficacy. So people are trying to use these agents early on, but they have to be comfortable in identifying them early on at the first headache or the slight change in mental status, the multiple neurotoxicity checks. With slight hypotension, if you miss that, then you’re dealing with grade 3. So if you are not in a setting where you can pick these things up early and intervene early, then you’re going to have to deal with a lot of difficult toxicities. And we did see that quick translation, and I’m sure this usage is just going to go up, and people need to be comfortable and in many places have doses of tocilizumab available before you give CAR therapy.

Michael Pulsipher, MD: Well you can’t get past the REMS program unless you have it available.

Nilanjan Ghosh, MD, PhD: Right, so those are things that are very important.

Matthew Lunning, DO: I think you hit it correctly, and you said “early.” But there’s a difference between that and prophylactic. And I think there’s a small experience with the axi-cel [axicabtagene ciloleucel] and early prophylactic tocilizumab use that may predict for more high-grade neurotoxicity. So early, yes; prophylactic, no.

Michael Pulsipher, MD: I think we need to be careful with these algorithms. If we give it too soon we may kill effector with that. And so if we’re going to be changing the algorithms very dramatically, we’ve got to study it, we’ve got to have a specific study.

David Maloney, MD, PhD: But this does lead to a lot of problems because if we actually look at the REMS programs, they’re different for each of these products. In fact, they’re telling you to do exactly different things at different times. And I think that what we’re seeing now in the real-world experience is that they’re converging more towards an earlier adoption of intervention to keep people out of the ICU, but this is going to require some further education.

Matthew Lunning, DO: Yes, if you get 3 constructs on the same floor, you almost need to have blue shirts, red shirts, green shirts.

Michael Pulsipher, MD: We have, because with the studies it’s equally an issue. You’re supposed to manage it according to what your study says. We have different outlines for each study and it’s a challenge.

Nilanjan Ghosh, MD, PhD: And then you add multiple diseases. Just imagine the complexities.

Transcript Edited for Clarity 
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