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Acute Lymphocytic Leukemia: What's Next

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: Friday, Mar 01, 2019



Transcript:

Mark R. Litzow, MD:
Well, this session has been extremely informative, and I’ve learned a lot today from each of you. Before we end the discussion, I’d like to get closing thoughts from each of our panelists. Jae, why don’t you start us off with your thoughts on where we go from here?

Jae Park, MD: Wow. So, I mean, I think in ALL, it’s very—I think leukemia in general has been such an exciting field to be part of for the last several years, [with] very new, novel therapies coming even within the same year, several of them. I think what I’m anticipating and what I’m excited about for the next several years is incorporating these novel therapies that we discussed before, a lot of which were immunotherapy for B[-cell] ALL, targeting CD22, CD19—or in the bispecific CAR [chimeric antigen receptor] T, we’re targeting 2 antigens at the same time. Are we going to get a better response?

I think the [challenge] that we are going to have—which is a good challenge, [a] good problem to have—is…, what is really the best way to combine this type of therapy to earlier lines in a setting [in which] we can move the curve from the 50[%] to 60%, cure 90% of what we want to and what we will take?

In a way, what I really dream about is…Currently, ALL therapy is very long. It’s about 3 years of a therapy for induction, consolidation, and maintenance. With this new therapy, do we really need that all 3 years? Wouldn’t that be great if we get 1 induction and then get either CAR T with some other novel therapy, that’s it. The higher-risk patients—because they are MRD [minimal residual disease] positive, are getting this novel therapy—may actually need a shorter therapy, because they can be done after maybe 3 months. Ideal situations, but I think that will make a huge difference in the patients’ quality of life if we can maintain…so that’s what I’m excited [about]—hopefully, we can see that, and what I’m excited about.

Mark R. Litzow, MD: Thank you. Bijal, what are your thoughts?

Bijal D. Shah, MD: I have to echo what Jae said. I’m excited about moving novel agents forward. I’m especially excited about what we’re generating in the CAR T space. I can absolutely envision a blin [blinatumomab] induction followed by a CAR T consolidation. I can envision randomized trials comparing CAR T against allogeneic transplant. I can envision all of these things because we’re in an era where we recognize [that] 50% ain’t good enough. We can do better. And we don’t have to hammer and hammer and hammer away before we apply these novel therapies.

And so I’m extremely excited about next-generation sequencing–based MRD approaches, because they’re going to allow us to move as we did with blinatumomab, to my surprise, as well. But we’re going to be able to move novel agents forward now using next-generation sequencing or other MRD-based approaches to guide the applications of some of these therapeutic approaches, as Jae alluded to. We’re going to get better at giving it. We’re going to get better at targeting it. And I think in 5 to 10 years, we’re going to [be] talking about what’s really just a novel, novel as a backbone for ALL therapy for the first time. And we can get away from discussions about this backbone versus that backbone.

Mark R. Litzow, MD: Anthony?

Anthony S. Stein, MD: Yeah, [what] I would like to see, probably in the 5 five years, is basically a regimen that avoids chemo, is a chemotherapy-free regimen. And I think there is 1 trial. The other point is—I mean, ALL is a relatively rare disease, so to make further advances, I think patients should be put on clinical trials, so that we can get an answer quicker and be able to move, to learn whether these novel agents can be moved into the up-front setting, and, hopefully, one day have a chemotherapy-free regimen, so we won’t be looking at all the toxicities from chemotherapy.

Mark R. Litzow, MD: Yeah. I would certainly echo that. I think of acute promyelocytic leukemia—used to be one of the worst prognostic leukemias. Now we’re not using traditional chemotherapy, and it’s got a very good prognosis. One thing we haven’t talked about a lot today is T-cell ALL, which I feel some sadness about in all the excitement with B-cell ALL. Nelarabine may be moving into the front-line setting, but that’s not going to be a major advance. There are some efforts with CAR T therapy with T-cell ALL. There [are] some other novel agents. Venetoclax might move into that space. So I think there’s hope with T-cell ALL, but we’ve got much more work to do to get to that point in T-cell ALL.

Anthony S. Stein, MD: Yeah. No, I echo that. I think especially early T-cell ALL is really an unmet need, and I think there are new, novel agents that are being looked at, such as daratumumab, and then the other one that you alluded to is basically venetoclax plus venetoclax as a combination. And that trial is now ongoing.

Mark R. Litzow, MD: Well, thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us, and we hope that you found this OncLive Peer Exchange® to be useful and informative. Thank you.

Transcript edited for clarity.

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Transcript:

Mark R. Litzow, MD:
Well, this session has been extremely informative, and I’ve learned a lot today from each of you. Before we end the discussion, I’d like to get closing thoughts from each of our panelists. Jae, why don’t you start us off with your thoughts on where we go from here?

Jae Park, MD: Wow. So, I mean, I think in ALL, it’s very—I think leukemia in general has been such an exciting field to be part of for the last several years, [with] very new, novel therapies coming even within the same year, several of them. I think what I’m anticipating and what I’m excited about for the next several years is incorporating these novel therapies that we discussed before, a lot of which were immunotherapy for B[-cell] ALL, targeting CD22, CD19—or in the bispecific CAR [chimeric antigen receptor] T, we’re targeting 2 antigens at the same time. Are we going to get a better response?

I think the [challenge] that we are going to have—which is a good challenge, [a] good problem to have—is…, what is really the best way to combine this type of therapy to earlier lines in a setting [in which] we can move the curve from the 50[%] to 60%, cure 90% of what we want to and what we will take?

In a way, what I really dream about is…Currently, ALL therapy is very long. It’s about 3 years of a therapy for induction, consolidation, and maintenance. With this new therapy, do we really need that all 3 years? Wouldn’t that be great if we get 1 induction and then get either CAR T with some other novel therapy, that’s it. The higher-risk patients—because they are MRD [minimal residual disease] positive, are getting this novel therapy—may actually need a shorter therapy, because they can be done after maybe 3 months. Ideal situations, but I think that will make a huge difference in the patients’ quality of life if we can maintain…so that’s what I’m excited [about]—hopefully, we can see that, and what I’m excited about.

Mark R. Litzow, MD: Thank you. Bijal, what are your thoughts?

Bijal D. Shah, MD: I have to echo what Jae said. I’m excited about moving novel agents forward. I’m especially excited about what we’re generating in the CAR T space. I can absolutely envision a blin [blinatumomab] induction followed by a CAR T consolidation. I can envision randomized trials comparing CAR T against allogeneic transplant. I can envision all of these things because we’re in an era where we recognize [that] 50% ain’t good enough. We can do better. And we don’t have to hammer and hammer and hammer away before we apply these novel therapies.

And so I’m extremely excited about next-generation sequencing–based MRD approaches, because they’re going to allow us to move as we did with blinatumomab, to my surprise, as well. But we’re going to be able to move novel agents forward now using next-generation sequencing or other MRD-based approaches to guide the applications of some of these therapeutic approaches, as Jae alluded to. We’re going to get better at giving it. We’re going to get better at targeting it. And I think in 5 to 10 years, we’re going to [be] talking about what’s really just a novel, novel as a backbone for ALL therapy for the first time. And we can get away from discussions about this backbone versus that backbone.

Mark R. Litzow, MD: Anthony?

Anthony S. Stein, MD: Yeah, [what] I would like to see, probably in the 5 five years, is basically a regimen that avoids chemo, is a chemotherapy-free regimen. And I think there is 1 trial. The other point is—I mean, ALL is a relatively rare disease, so to make further advances, I think patients should be put on clinical trials, so that we can get an answer quicker and be able to move, to learn whether these novel agents can be moved into the up-front setting, and, hopefully, one day have a chemotherapy-free regimen, so we won’t be looking at all the toxicities from chemotherapy.

Mark R. Litzow, MD: Yeah. I would certainly echo that. I think of acute promyelocytic leukemia—used to be one of the worst prognostic leukemias. Now we’re not using traditional chemotherapy, and it’s got a very good prognosis. One thing we haven’t talked about a lot today is T-cell ALL, which I feel some sadness about in all the excitement with B-cell ALL. Nelarabine may be moving into the front-line setting, but that’s not going to be a major advance. There are some efforts with CAR T therapy with T-cell ALL. There [are] some other novel agents. Venetoclax might move into that space. So I think there’s hope with T-cell ALL, but we’ve got much more work to do to get to that point in T-cell ALL.

Anthony S. Stein, MD: Yeah. No, I echo that. I think especially early T-cell ALL is really an unmet need, and I think there are new, novel agents that are being looked at, such as daratumumab, and then the other one that you alluded to is basically venetoclax plus venetoclax as a combination. And that trial is now ongoing.

Mark R. Litzow, MD: Well, thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us, and we hope that you found this OncLive Peer Exchange® to be useful and informative. Thank you.

Transcript edited for clarity.
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