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Relapse Type and Monoclonal Antibody Choice in Multiple Myeloma

Insights From:Jatin P. Shah, MD, MD Anderson Cancer Center;Ivan Marques Borrello, MD, Johns Hopkins University;James R. Berenson, MD, Institute for Myeloma and Bone Cancer Research
Published: Wednesday, Sep 07, 2016


Transcript:

Ivan Marques Borrello, MD:
The use of monoclonal antibodies in relapsed disease, especially now that we have two of them, can vary depending upon how patients are actually relapsing. I think what we’ve seen with the ELOQUENT trial is that this is an antibody that is probably best suited for patients with a slow, progressive biochemical relapse as opposed to much more of symptomatic relapse. The data that were shown at the plenary session of ASCO and this meeting shows rather significant response with daratumumab/Velcade/dexamethasone, which would seem to suggest that maybe if a more rapid response is needed, daratumumab may be more of the antibody of choice. And so, looking at this, the slow biochemical (the maintenance) setting is maybe one that’s more appropriate for a monoclonal antibody such as elotuzumab, in contrast to a more aggressive setting, maybe one in which the antibody such as daratumumab could be more effectively integrated.

We’re now dealing with two antibodies that are FDA approved, and I would not be surprised if over the next few years we see many more. And some of the questions asked oftentimes are, how do you use all of these drugs, how do you sequence them, and is there any kind of cross reactivity? I think these are very interesting and important questions. Unfortunately, they’re questions for which right now we don’t have data. There is no reason to suspect that the use of one would preclude the use of the other one, specifically because the targets are completely different. In the case of the two that are currently approved, one targets CD38, the other one targets 9F7; clearly two very different antibodies and two different targets. So, it would not be unreasonable to think that one, either one, could be followed by the other one. You could, theoretically, also hypothesize that you could use both of them together. But, again, in the absence of data, I wouldn’t recommend any of these things at this point, because we just don’t have that data.

James R. Berenson, MD: Natural killer cells are an important part of the immune response against myeloma. And, clearly, myeloma patients are negatively impacted. They don’t have as many and they don’t work as well. And elotuzumab, through this SLAMF7 binding, does activate NK cells, and that effect allows us to gobble up myeloma and get rid of it. In terms of timing of where to use it, whether it would be better to use it when there’s none and so you can activate it, or use it earlier when they’re still around, I think it’s an open question. But, clearly there are additional benefits of elotuzumab beyond simply targeting the myeloma cell itself. Because, without the addition and the troops of the immune system coming along, it really doesn’t work very well. So, it needs the immune system to come along. Activating that is an important part of the picture, but whether it should be done earlier or later in the disease, I don’t think we really know.

The use of antibody-based therapy has the distinct advantage, it’s not very toxic; toxicity all being upfront. Maybe you have an infusion reaction. After that, maybe a slight increased risk of infection. There isn’t much there. So, it makes it an ideal partner to combine with about anything. Whether it’s going to turn out to be better to use elotuzumab or daratumumab with individual drugs that are already approved, or actually together, the jury’s out on this. I think patients will end up getting everything. And, I’ve had that occur recently in the clinic. I had a patient who, for example, was just really allergic to daratumumab. I just slipped in elotuzumab and the guy’s done amazing, and he’s seen everything. And it’s multiple of many drugs together, but the patient had seen all those other drugs without elotuzumab and the elotuzumab added no toxicity. I think we’re going to see that with daratumumab, as well. I think we’re going to see people getting really creative with their recipes over the next few years with these drugs, and recognize that they are a very important part of the armamentarium to treat myeloma today.

Transcript Edited for Clarity
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Transcript:

Ivan Marques Borrello, MD:
The use of monoclonal antibodies in relapsed disease, especially now that we have two of them, can vary depending upon how patients are actually relapsing. I think what we’ve seen with the ELOQUENT trial is that this is an antibody that is probably best suited for patients with a slow, progressive biochemical relapse as opposed to much more of symptomatic relapse. The data that were shown at the plenary session of ASCO and this meeting shows rather significant response with daratumumab/Velcade/dexamethasone, which would seem to suggest that maybe if a more rapid response is needed, daratumumab may be more of the antibody of choice. And so, looking at this, the slow biochemical (the maintenance) setting is maybe one that’s more appropriate for a monoclonal antibody such as elotuzumab, in contrast to a more aggressive setting, maybe one in which the antibody such as daratumumab could be more effectively integrated.

We’re now dealing with two antibodies that are FDA approved, and I would not be surprised if over the next few years we see many more. And some of the questions asked oftentimes are, how do you use all of these drugs, how do you sequence them, and is there any kind of cross reactivity? I think these are very interesting and important questions. Unfortunately, they’re questions for which right now we don’t have data. There is no reason to suspect that the use of one would preclude the use of the other one, specifically because the targets are completely different. In the case of the two that are currently approved, one targets CD38, the other one targets 9F7; clearly two very different antibodies and two different targets. So, it would not be unreasonable to think that one, either one, could be followed by the other one. You could, theoretically, also hypothesize that you could use both of them together. But, again, in the absence of data, I wouldn’t recommend any of these things at this point, because we just don’t have that data.

James R. Berenson, MD: Natural killer cells are an important part of the immune response against myeloma. And, clearly, myeloma patients are negatively impacted. They don’t have as many and they don’t work as well. And elotuzumab, through this SLAMF7 binding, does activate NK cells, and that effect allows us to gobble up myeloma and get rid of it. In terms of timing of where to use it, whether it would be better to use it when there’s none and so you can activate it, or use it earlier when they’re still around, I think it’s an open question. But, clearly there are additional benefits of elotuzumab beyond simply targeting the myeloma cell itself. Because, without the addition and the troops of the immune system coming along, it really doesn’t work very well. So, it needs the immune system to come along. Activating that is an important part of the picture, but whether it should be done earlier or later in the disease, I don’t think we really know.

The use of antibody-based therapy has the distinct advantage, it’s not very toxic; toxicity all being upfront. Maybe you have an infusion reaction. After that, maybe a slight increased risk of infection. There isn’t much there. So, it makes it an ideal partner to combine with about anything. Whether it’s going to turn out to be better to use elotuzumab or daratumumab with individual drugs that are already approved, or actually together, the jury’s out on this. I think patients will end up getting everything. And, I’ve had that occur recently in the clinic. I had a patient who, for example, was just really allergic to daratumumab. I just slipped in elotuzumab and the guy’s done amazing, and he’s seen everything. And it’s multiple of many drugs together, but the patient had seen all those other drugs without elotuzumab and the elotuzumab added no toxicity. I think we’re going to see that with daratumumab, as well. I think we’re going to see people getting really creative with their recipes over the next few years with these drugs, and recognize that they are a very important part of the armamentarium to treat myeloma today.

Transcript Edited for Clarity
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