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Potential Use of CAR T-Cell Therapy Earlier in Sequencing

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: Monday, Jan 21, 2019



Transcript: 

David Maloney, MD, PhD: Can we move this up even earlier, do you think? We’re going to take on transplant. That’s the second thing. So do you think there’s a future without aggressive chemotherapy?

Leo I. Gordon, MD, FACP: I don’t know. I think there might be, and I think we don’t have the data to say that yet, obviously. Still we are, I think, curing the majority of patients with diffuse large B-cell lymphoma in the Rituxan era. But we are beginning to identify a higher risk group of patients that we know aren’t going to do as well, those patients with double- or triple-hit lymphomas, MYC mutations, those people with high LDH [lactate dehydrogenase], which I think is still one of the best predictors of aggressiveness of the disease. And you would like to at least consider the possibility of an earlier intervention in those patients, whether it’s a couple of cycles of chemotherapy followed by CAR T. I think there are some trials that are beginning to ask that question.

Matthew Lunning, DO: Yes, I think if you look at the time of diagnosis to identify, let’s just say, double-hit lymphoma, and then if you meld that with the PETAL data and you’re PET-4 [positron emission tomography-4]—you’re still positive and you’re a double-hit—I can imagine a world where I would consider at that time point to take them and not go to cycle 5 and 6. If it’s dose adjusted, you’re stopping them at dose level 3 at that time point and transitioning that patient towards a CAR T.

Michael Pulsipher, MD: I think getting to really lower risk and much earlier patients, we’ve got to have a better safety profile. And we have to have a financial toxicity profile if it’s going to fit them.

Nilanjan Ghosh, MD, PhD: The right population is important, but when you have a primary refractory patient and they are refractory to second-line therapy, as the disease grows and it gets more bulky, we see now with our experience that even with bulky tumors sometimes the tumor gets hot: you can see an initial response and everything. But it seems like through some mechanism, maybe T cell exhaustion or something else, that the relapse rate just seems to be higher with bulky disease, even though you can almost see it get better immediately, maybe even within the first week or so. That tells us that if we know somebody is primary refractory, them being refractory again to the second-line therapy and then waiting would just mean adding more tumor bulk. Even then we are seeing responders. But, we could catch those people early and intervene early, and there are trials now looking at both frontline patients who are transplant eligible and frontline patients who are not transplant eligible, but who have somewhat of a performance status and organ function to get a CAR T therapy. When those trials read out, I would imagine that we would have good results.

David Maloney, MD, PhD: So you’re arguing for a much earlier referral to the treatment center.

Nilanjan Ghosh, MD, PhD: Absolutely.

David Maloney, MD, PhD: We need to get these patients in faster. They need to be seen at the treatment centers.

Nilanjan Ghosh, MD, PhD: One of the things that we’ve talked about, at least in our surrounding community and referral practices, is to have the referral early on. Being a transplant and CAR T center, if someone got started on RICE [rituximab/ifosfamide/carboplatin/etoposide] and they had a really good remission, we may be able to have the discussion of transplant early on. And, if they are not there, they may be on the CAR T list. But at least that planning can start when they’re getting their first salvage therapy, and they could go 1 of those 2 ways. Rather than waiting till the whole response assessment is done and then starting that process, we’re now dealing with the whole next line of therapy.

Transcript Edited for Clarity 

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Transcript: 

David Maloney, MD, PhD: Can we move this up even earlier, do you think? We’re going to take on transplant. That’s the second thing. So do you think there’s a future without aggressive chemotherapy?

Leo I. Gordon, MD, FACP: I don’t know. I think there might be, and I think we don’t have the data to say that yet, obviously. Still we are, I think, curing the majority of patients with diffuse large B-cell lymphoma in the Rituxan era. But we are beginning to identify a higher risk group of patients that we know aren’t going to do as well, those patients with double- or triple-hit lymphomas, MYC mutations, those people with high LDH [lactate dehydrogenase], which I think is still one of the best predictors of aggressiveness of the disease. And you would like to at least consider the possibility of an earlier intervention in those patients, whether it’s a couple of cycles of chemotherapy followed by CAR T. I think there are some trials that are beginning to ask that question.

Matthew Lunning, DO: Yes, I think if you look at the time of diagnosis to identify, let’s just say, double-hit lymphoma, and then if you meld that with the PETAL data and you’re PET-4 [positron emission tomography-4]—you’re still positive and you’re a double-hit—I can imagine a world where I would consider at that time point to take them and not go to cycle 5 and 6. If it’s dose adjusted, you’re stopping them at dose level 3 at that time point and transitioning that patient towards a CAR T.

Michael Pulsipher, MD: I think getting to really lower risk and much earlier patients, we’ve got to have a better safety profile. And we have to have a financial toxicity profile if it’s going to fit them.

Nilanjan Ghosh, MD, PhD: The right population is important, but when you have a primary refractory patient and they are refractory to second-line therapy, as the disease grows and it gets more bulky, we see now with our experience that even with bulky tumors sometimes the tumor gets hot: you can see an initial response and everything. But it seems like through some mechanism, maybe T cell exhaustion or something else, that the relapse rate just seems to be higher with bulky disease, even though you can almost see it get better immediately, maybe even within the first week or so. That tells us that if we know somebody is primary refractory, them being refractory again to the second-line therapy and then waiting would just mean adding more tumor bulk. Even then we are seeing responders. But, we could catch those people early and intervene early, and there are trials now looking at both frontline patients who are transplant eligible and frontline patients who are not transplant eligible, but who have somewhat of a performance status and organ function to get a CAR T therapy. When those trials read out, I would imagine that we would have good results.

David Maloney, MD, PhD: So you’re arguing for a much earlier referral to the treatment center.

Nilanjan Ghosh, MD, PhD: Absolutely.

David Maloney, MD, PhD: We need to get these patients in faster. They need to be seen at the treatment centers.

Nilanjan Ghosh, MD, PhD: One of the things that we’ve talked about, at least in our surrounding community and referral practices, is to have the referral early on. Being a transplant and CAR T center, if someone got started on RICE [rituximab/ifosfamide/carboplatin/etoposide] and they had a really good remission, we may be able to have the discussion of transplant early on. And, if they are not there, they may be on the CAR T list. But at least that planning can start when they’re getting their first salvage therapy, and they could go 1 of those 2 ways. Rather than waiting till the whole response assessment is done and then starting that process, we’re now dealing with the whole next line of therapy.

Transcript Edited for Clarity 
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