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Antibody-Drug Conjugates in Myeloma

Insights From: Robert L. Ferris, MD, PhD, UPMC Hillman Cancer Center; Anna C. Pavlick, DO, NYU Langone Hospitals
Published: Thursday, Mar 07, 2019



Transcript:

A. Keith Stewart, MB, ChB:
Let’s close with BCMA [B-cell maturation antigen] as a target, which I think has got everybody excited. And let’s talk a little bit first about antibody-drug conjugates, Faith. Do you have any experience with the BCMA antibody-drug conjugate yet?

Faith Davies, MD, MBBCh, MRCP, FRCPath: No, but I’ve been looking at the literature. It looks really very impressive.

A. Keith Stewart, MB, ChB: Tell the audience what’s got you excited there.

Faith Davies, MD, MBBCh, MRCP, FRCPath: Suzanne Trudel, MD, presented the initial data. There were 60% response rates with the antibody-drug conjugate and very good tolerability. I think there are a few unusual adverse effects attached to it, which, just as with all the other drugs, we’re going to need to learn how to manage them, and moving forward and so on. But it seems to be that it works very well in this whole concept of having your payload on your antibody. It seems to be opening up.....

A. Keith Stewart, MB, ChB: It seems to validate BCMA as a target.

Faith Davies, MD, MBBCh, MRCP, FRCPath: Definitely.

A. Keith Stewart, MB, ChB: We are just opening the clinical trials now, but has anybody had an opportunity to use the drug?

Adriana Rossi, MD: We’re opening it as well. So not yet.

A. Keith Stewart, MB, ChB: It looks very exciting—60% response rate in fairly heavily pretreated patients and some corneal toxicity but otherwise people are getting through it. So BCMA is now validated as a target thanks to that drug. And there’s some very exciting data being presented at this meeting about a BiTE [bispecific T-cell engager] molecule from Amgen actually. But there are others out there. There are probably a dozen of these drugs now in clinical trials.

We haven’t seen the updated data, but in the abstract it looks like there are some very deep responses with an anti-BCMA BiTE, which, of course, I think in that study was a continuous infusion, but they are now being studied as a weekly dosing schedule. Does anyone want to take a crack at your enthusiasm for that?

Rafael Fonseca, MD: Sure. So a BCMA, based on the study we’re talking about, short-lived, and escalation, as they get into the higher doses….

A. Keith Stewart, MB, ChB: What do you mean by short-lived?

Rafael Fonseca, MD: Short-lived half-life for the antibody. But it’s, again, to high doses. They’re seeing CR [complete response], so MRD [minimal residual disease]-negative status. I think the proof of principle is there. That’s why there’s so much excitement, even with a phase I trial. BiTEs potentially could be a major competitor to CAR [chimeric antigen receptor] T cells because you know we engineer those T cells to recognize the cells, and I describe the BiTEs, there’s like double-sided Velcro straps, you know, the 1 side you have the myeloma, the other side you have the T cell, but they’re off the shelf. You can start treating a person the day you decide to start treatment.

A. Keith Stewart, MB, ChB: Faith, are you excited about the BiTEs?

Faith Davies, MD, MBBCh, MRCP, FRCPath: Yes. We’re involved in the once-weekly study, which hasn’t reported its data yet. But I think that continuous schedule is great. There were, as we see with the CAR T cells, again, an unusual set of adverse effects, so we have to be careful.

A. Keith Stewart, MB, ChB: I haven’t read the abstract carefully enough. What does it say in there about cytokine release syndrome?

Faith Davies, MD, MBBCh, MRCP, FRCPath: It does occur. It’s manageable, but it definitely occurs. And I guess that’s part of the question.

Rafael Fonseca, MD: That’s part of the magic of these therapies.

Faith Davies, MD, MBBCh, MRCP, FRCPath: I’m not sure you get a response without. You know, there’s always some form of toxicity, unfortunately.

A. Keith Stewart, MB, ChB: So pretty early days but it’s like the equivalent of blinatumomab for acute leukemia. It looks like we’ve got some of those drugs coming.

Transcript edited for clarity.

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Transcript:

A. Keith Stewart, MB, ChB:
Let’s close with BCMA [B-cell maturation antigen] as a target, which I think has got everybody excited. And let’s talk a little bit first about antibody-drug conjugates, Faith. Do you have any experience with the BCMA antibody-drug conjugate yet?

Faith Davies, MD, MBBCh, MRCP, FRCPath: No, but I’ve been looking at the literature. It looks really very impressive.

A. Keith Stewart, MB, ChB: Tell the audience what’s got you excited there.

Faith Davies, MD, MBBCh, MRCP, FRCPath: Suzanne Trudel, MD, presented the initial data. There were 60% response rates with the antibody-drug conjugate and very good tolerability. I think there are a few unusual adverse effects attached to it, which, just as with all the other drugs, we’re going to need to learn how to manage them, and moving forward and so on. But it seems to be that it works very well in this whole concept of having your payload on your antibody. It seems to be opening up.....

A. Keith Stewart, MB, ChB: It seems to validate BCMA as a target.

Faith Davies, MD, MBBCh, MRCP, FRCPath: Definitely.

A. Keith Stewart, MB, ChB: We are just opening the clinical trials now, but has anybody had an opportunity to use the drug?

Adriana Rossi, MD: We’re opening it as well. So not yet.

A. Keith Stewart, MB, ChB: It looks very exciting—60% response rate in fairly heavily pretreated patients and some corneal toxicity but otherwise people are getting through it. So BCMA is now validated as a target thanks to that drug. And there’s some very exciting data being presented at this meeting about a BiTE [bispecific T-cell engager] molecule from Amgen actually. But there are others out there. There are probably a dozen of these drugs now in clinical trials.

We haven’t seen the updated data, but in the abstract it looks like there are some very deep responses with an anti-BCMA BiTE, which, of course, I think in that study was a continuous infusion, but they are now being studied as a weekly dosing schedule. Does anyone want to take a crack at your enthusiasm for that?

Rafael Fonseca, MD: Sure. So a BCMA, based on the study we’re talking about, short-lived, and escalation, as they get into the higher doses….

A. Keith Stewart, MB, ChB: What do you mean by short-lived?

Rafael Fonseca, MD: Short-lived half-life for the antibody. But it’s, again, to high doses. They’re seeing CR [complete response], so MRD [minimal residual disease]-negative status. I think the proof of principle is there. That’s why there’s so much excitement, even with a phase I trial. BiTEs potentially could be a major competitor to CAR [chimeric antigen receptor] T cells because you know we engineer those T cells to recognize the cells, and I describe the BiTEs, there’s like double-sided Velcro straps, you know, the 1 side you have the myeloma, the other side you have the T cell, but they’re off the shelf. You can start treating a person the day you decide to start treatment.

A. Keith Stewart, MB, ChB: Faith, are you excited about the BiTEs?

Faith Davies, MD, MBBCh, MRCP, FRCPath: Yes. We’re involved in the once-weekly study, which hasn’t reported its data yet. But I think that continuous schedule is great. There were, as we see with the CAR T cells, again, an unusual set of adverse effects, so we have to be careful.

A. Keith Stewart, MB, ChB: I haven’t read the abstract carefully enough. What does it say in there about cytokine release syndrome?

Faith Davies, MD, MBBCh, MRCP, FRCPath: It does occur. It’s manageable, but it definitely occurs. And I guess that’s part of the question.

Rafael Fonseca, MD: That’s part of the magic of these therapies.

Faith Davies, MD, MBBCh, MRCP, FRCPath: I’m not sure you get a response without. You know, there’s always some form of toxicity, unfortunately.

A. Keith Stewart, MB, ChB: So pretty early days but it’s like the equivalent of blinatumomab for acute leukemia. It looks like we’ve got some of those drugs coming.

Transcript edited for clarity.
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