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Considerations of Cytoreduction in ALL

Panelists: Mark R. Litzow, MD, The Mayo Clinic; Jae Park, MD, Memorial Sloan Kettering Cancer Center; Bijal Shah, MD H. Lee Moffitt Cancer Center & Research Institute; Anthony Stein Gehr Family Center for Leukemia Research
Published: Wednesday, Jan 30, 2019



Transcript: 

Bijal D. Shah, MD:
Jae, did you have to cytoreduce any of the patients before they got the blinatumomab?

Jae Park, MD: They’re able to receive steroid or hydroxyurea to get the disease burden down at the beginning. I think there will be another approach to think about, even though this [did not have] Cytoxan or other chemotherapy approaches built into it. But if we’re able to get the disease burden down at the very beginning, [we will see] whether you can increase upon the response rates. I think what we are seeing with the relapsed data, the higher the disease burden in the blinatumomab may not have as good of an activity in those inducing complete response rates.

Because it’s newly diagnosed and a high disease burden setting, especially if they had a high circulating blast, I think we know that these patients may not do as well unless they get some degree of a cytoreduction. So we cover steroid. I don’t think we need to get that many. These are treatment naïve patients so it’s a steroid, and vincristine alone may be effective, or some other regimen. So in the future I think if we were to do that, we may actually even get, hopefully, a better response.

Bijal D. Shah, MD: It’s very encouraging to go from 40% to 65%, particularly in a patient population that may not be fit for therapy; [it] is something to be proud of.

Anthony S. Stein, MD: Yes, and of note also, most of the patients who got a complete remission, I think 92% became MRD [minimal residual disease]-negative as well.

Mark R. Litzow, MD: It’s a very good point.

Jae Park, MD: And very few [cases of] induction mortality, which is what we also worry about in this patient population. So I think that proves the point that once you have effective but less intense or less toxic therapy, then your treatment paradigm, how you approach these patients, really changes.

Bijal D. Shah, MD: Would you do it in a young adult?

Jae Park, MD: Young adult patients?

Bijal D. Shah, MD: If a 65% CR rate, knowing that you had chemotherapy as an option should they fail, would you be willing to approach a young adult now with blinatumomab—65%; 92% are MRD-negative.

Jae Park, MD:  I think young adults, these patients have other options there too, and we know from the historical data and the current data that we can actually get over 90% complete response rate. So 60%, 65% in older ALL patients were not able to tolerate the other type of a therapeutic regimen. It’s very encouraging; it’s better than what we were seeing before.

In younger adults I don’t think it’s good enough, certainly not good enough that we’re seeing 90%....  And I don’t know whether we have to stick with the chemotherapy forever in these patients, because, as you said, even though the CR rate is high, relapses are common in that we’re curing maybe 50%, and hopefully 60%, upwards of 60% of the patients. So there’s definitely room for improvement in those patient populations for incorporation of these novel agents. But in younger adults, however we define younger–60, 65–if they’re able to tolerate either pediatric-inspired chemotherapy, pediatric regimen, or hyper-CVAD, those patients should receive it. Whether by itself or adding these agents on top of it to improve them further, is, I think what we are going to see in the very near future.

Mark R. Litzow, MD: I agree with Jae. I don’t think we’re there yet, but I think it could be the wave of the future.


Transcript Edited for Clarity

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Transcript: 

Bijal D. Shah, MD:
Jae, did you have to cytoreduce any of the patients before they got the blinatumomab?

Jae Park, MD: They’re able to receive steroid or hydroxyurea to get the disease burden down at the beginning. I think there will be another approach to think about, even though this [did not have] Cytoxan or other chemotherapy approaches built into it. But if we’re able to get the disease burden down at the very beginning, [we will see] whether you can increase upon the response rates. I think what we are seeing with the relapsed data, the higher the disease burden in the blinatumomab may not have as good of an activity in those inducing complete response rates.

Because it’s newly diagnosed and a high disease burden setting, especially if they had a high circulating blast, I think we know that these patients may not do as well unless they get some degree of a cytoreduction. So we cover steroid. I don’t think we need to get that many. These are treatment naïve patients so it’s a steroid, and vincristine alone may be effective, or some other regimen. So in the future I think if we were to do that, we may actually even get, hopefully, a better response.

Bijal D. Shah, MD: It’s very encouraging to go from 40% to 65%, particularly in a patient population that may not be fit for therapy; [it] is something to be proud of.

Anthony S. Stein, MD: Yes, and of note also, most of the patients who got a complete remission, I think 92% became MRD [minimal residual disease]-negative as well.

Mark R. Litzow, MD: It’s a very good point.

Jae Park, MD: And very few [cases of] induction mortality, which is what we also worry about in this patient population. So I think that proves the point that once you have effective but less intense or less toxic therapy, then your treatment paradigm, how you approach these patients, really changes.

Bijal D. Shah, MD: Would you do it in a young adult?

Jae Park, MD: Young adult patients?

Bijal D. Shah, MD: If a 65% CR rate, knowing that you had chemotherapy as an option should they fail, would you be willing to approach a young adult now with blinatumomab—65%; 92% are MRD-negative.

Jae Park, MD:  I think young adults, these patients have other options there too, and we know from the historical data and the current data that we can actually get over 90% complete response rate. So 60%, 65% in older ALL patients were not able to tolerate the other type of a therapeutic regimen. It’s very encouraging; it’s better than what we were seeing before.

In younger adults I don’t think it’s good enough, certainly not good enough that we’re seeing 90%....  And I don’t know whether we have to stick with the chemotherapy forever in these patients, because, as you said, even though the CR rate is high, relapses are common in that we’re curing maybe 50%, and hopefully 60%, upwards of 60% of the patients. So there’s definitely room for improvement in those patient populations for incorporation of these novel agents. But in younger adults, however we define younger–60, 65–if they’re able to tolerate either pediatric-inspired chemotherapy, pediatric regimen, or hyper-CVAD, those patients should receive it. Whether by itself or adding these agents on top of it to improve them further, is, I think what we are going to see in the very near future.

Mark R. Litzow, MD: I agree with Jae. I don’t think we’re there yet, but I think it could be the wave of the future.


Transcript Edited for Clarity
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