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Considerations for Autologous Stem Cell Transplantation

Panelists: Alexey V. Danilov, MD, PhD, Oregon Health & Science University; Andre Goy, MD, Hackensack University Medical Center; John P. Leonard, MD, New York-Presbyterian/Weill Cornell Medical Center; John M. Pagel, MD, PhD, DSc, Swedish Medical Center Seattle and Issaquah; Stephen J. Schuster, MD, The University of Pennsylvania
Published: Wednesday, Jan 10, 2018



Transcript: 

John P. Leonard, MD: You mentioned AraC. Most of the argument, at this point for AraC, although it’s evolving, is the fact that there are higher rates of MRD negativity. We now have a national trial going on that basically says you can give patients any induction therapy that you want and can assess their MRD status. The MRD-positive patients are going on to transplant, and the MRD-negative patients are being randomized between rituximab maintenance and autologous transplant. What we can do, and do we need to continue with an autologous transplant if you’re MRD-negative, which is what it has been in myeloma? Are you using MRD, at this point, in your patients?

Stephen J. Schuster, MD: Not outside the setting of a trial, at this point.

John P. Leonard, MD: Alexey, how do you follow these patients? I’m kind of a minimalist from the standpoint of, if patients are doing well and are in remission, we’ve moved away from scans in a lot of situations in large cell lymphoma. Once you have a negative PET scan and end treatment, I think there’s an argument. There was an abstract presented suggesting that in follicular lymphoma, when reviewing the value of PET, most relapses occur only in surveillance scans. And in follicular lymphoma, only about 4% of scans had anything meaningful. What about mantle cell lymphoma? Do you do a lot of scans in these patients?

Alexey V. Danilov, MD, PhD: No, I do not. I think it would be difficult to run such a trial in mantle cell lymphoma. I essentially apply the data in more aggressive lymphomas.

John P. Leonard, MD: John, your thoughts on scanning? How do you scan these patients?

John M. Pagel, MD, PhD, DSc: We overdo scans. I’m a fan of fewer scans. Patients are a fan of fewer scans. I think we should do exactly as Alexey is saying, follow the large cell and make a more aggressive approach.

John P. Leonard, MD: We’ve talked about autologous transplant. Andre, you referenced the Gerson study which looked at autologous transplantation as a target. What do you tell a patient, John, from the standpoint of receiving an autologous transplant? Do you expect for that patient to live longer with an autologous transplant? Do you think they’re just going to be in remission longer? In the absence of really good modern randomized trial data, this retrospective data, what’s your conversation about with the patient?

John M. Pagel, MD, PhD, DSc: I think the goal of the transplant is to provide the longest remission we can get for patients. The best chance to do that is in that very first remission. Andre alluded to that, of course, as well. Transplant is an option for the patients. It is true that it’s very controversial. This abstract that you alluded to paints that picture. It was an abstract for about 1000 patients or so, and it looked at a series of patients in a retrospective fashion. They got a transplant, or didn’t. Of course, the ones who got a transplant did better. Why did they do better? They did better because they were the more fit patients. They were the younger patients. They were the ones who could get more intensive therapy.

In fact, if you look at the patients who didn’t get a transplant, about 70% of them didn’t get a transplant because either the doctor or the patient didn’t think it was appropriate. So, it tells you that the patient population is very, very different. That being said, if you’re really looking to get the best outcome you can in a younger patient, you’ve got one chance at that autologous transplant, perhaps. I think it’s a very important conversation to have with patients, about the pluses and minuses.

With transplant, it is important to remember that this usually corresponds with fairly low morbidity. Most autologous transplants that we do are done as outpatient procedures. The risk of having a life-threatening complication is less than 1%. It is not to say that people don’t get sick, but people, especially younger, more fit patients, do well and can get through that.

Andre Goy, MD: I was just going to mention that there was another study that was published from the SEER (Surveillance, Epidemiology, and End Results Program) database. Obviously, the progression-free survival was 3 times better in the intensive or high-dose therapy approach, compared to R-CHOP. But if you pull the high-dose therapy or intensive therapy together, there was a clear survival advantage. So, I think this is to the point that you alluded to, John. At the time, we really didn’t use maintenance. This was something that clearly gave us a longer duration. The maintenance, particularly now that we have MRD, is going to raise a really good question. And then, the European group is looking at a different way to look at that, by incorporating ibrutinib in leukemia, ibrutinib consolidation/maintenance, versus high dose transplant. So, I think that we have to really put in perspective that we now have different approaches that might really change the way we think.

Transcript Edited for Clarity 

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Transcript: 

John P. Leonard, MD: You mentioned AraC. Most of the argument, at this point for AraC, although it’s evolving, is the fact that there are higher rates of MRD negativity. We now have a national trial going on that basically says you can give patients any induction therapy that you want and can assess their MRD status. The MRD-positive patients are going on to transplant, and the MRD-negative patients are being randomized between rituximab maintenance and autologous transplant. What we can do, and do we need to continue with an autologous transplant if you’re MRD-negative, which is what it has been in myeloma? Are you using MRD, at this point, in your patients?

Stephen J. Schuster, MD: Not outside the setting of a trial, at this point.

John P. Leonard, MD: Alexey, how do you follow these patients? I’m kind of a minimalist from the standpoint of, if patients are doing well and are in remission, we’ve moved away from scans in a lot of situations in large cell lymphoma. Once you have a negative PET scan and end treatment, I think there’s an argument. There was an abstract presented suggesting that in follicular lymphoma, when reviewing the value of PET, most relapses occur only in surveillance scans. And in follicular lymphoma, only about 4% of scans had anything meaningful. What about mantle cell lymphoma? Do you do a lot of scans in these patients?

Alexey V. Danilov, MD, PhD: No, I do not. I think it would be difficult to run such a trial in mantle cell lymphoma. I essentially apply the data in more aggressive lymphomas.

John P. Leonard, MD: John, your thoughts on scanning? How do you scan these patients?

John M. Pagel, MD, PhD, DSc: We overdo scans. I’m a fan of fewer scans. Patients are a fan of fewer scans. I think we should do exactly as Alexey is saying, follow the large cell and make a more aggressive approach.

John P. Leonard, MD: We’ve talked about autologous transplant. Andre, you referenced the Gerson study which looked at autologous transplantation as a target. What do you tell a patient, John, from the standpoint of receiving an autologous transplant? Do you expect for that patient to live longer with an autologous transplant? Do you think they’re just going to be in remission longer? In the absence of really good modern randomized trial data, this retrospective data, what’s your conversation about with the patient?

John M. Pagel, MD, PhD, DSc: I think the goal of the transplant is to provide the longest remission we can get for patients. The best chance to do that is in that very first remission. Andre alluded to that, of course, as well. Transplant is an option for the patients. It is true that it’s very controversial. This abstract that you alluded to paints that picture. It was an abstract for about 1000 patients or so, and it looked at a series of patients in a retrospective fashion. They got a transplant, or didn’t. Of course, the ones who got a transplant did better. Why did they do better? They did better because they were the more fit patients. They were the younger patients. They were the ones who could get more intensive therapy.

In fact, if you look at the patients who didn’t get a transplant, about 70% of them didn’t get a transplant because either the doctor or the patient didn’t think it was appropriate. So, it tells you that the patient population is very, very different. That being said, if you’re really looking to get the best outcome you can in a younger patient, you’ve got one chance at that autologous transplant, perhaps. I think it’s a very important conversation to have with patients, about the pluses and minuses.

With transplant, it is important to remember that this usually corresponds with fairly low morbidity. Most autologous transplants that we do are done as outpatient procedures. The risk of having a life-threatening complication is less than 1%. It is not to say that people don’t get sick, but people, especially younger, more fit patients, do well and can get through that.

Andre Goy, MD: I was just going to mention that there was another study that was published from the SEER (Surveillance, Epidemiology, and End Results Program) database. Obviously, the progression-free survival was 3 times better in the intensive or high-dose therapy approach, compared to R-CHOP. But if you pull the high-dose therapy or intensive therapy together, there was a clear survival advantage. So, I think this is to the point that you alluded to, John. At the time, we really didn’t use maintenance. This was something that clearly gave us a longer duration. The maintenance, particularly now that we have MRD, is going to raise a really good question. And then, the European group is looking at a different way to look at that, by incorporating ibrutinib in leukemia, ibrutinib consolidation/maintenance, versus high dose transplant. So, I think that we have to really put in perspective that we now have different approaches that might really change the way we think.

Transcript Edited for Clarity 
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