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New Data for Newly Diagnosed Myeloma

Panelists: Keith Stewart, MB, CHB, Mayo Clinic; Sagar Lonial, MD, Winship Cancer Institute; Paul Richardson, MD, Dana-Farber Cancer Institute; Amrita Krishnan, MD, City of Hope Comprehensive Cancer Center; Saad Usmani, MD, Levine Cancer Institute
Published: Tuesday, Jan 24, 2017



Transcript:

Keith Stewart, MB, CHB:
Let’s move on now. We’ll talk about how we treat newly-diagnosed symptomatic patients. So, these are patients who clearly need therapy. Saad, we’ll start with you. What factors do you consider when determining the most appropriate upfront therapy for your younger transplant-eligible patients?

Saad Usmani, MD: The general approach for the transplant-eligible patients is a triplet regimen across the board.

Keith Stewart, MB, CHB: Triplet of what?

Saad Usmani, MD: Of lenalidomide/bortezomib/dexamethasone (RVD). There are certain situations where you need therapy quickly, for example, a patient who is presenting with renal insufficiency, getting admitted to the hospital, and that’s how they’re being diagnosed. You might reach for a regimen that includes bortezomib/cyclophosphamide/dexamethasone to begin with.

Keith Stewart, MB, CHB: So, patients with renal failure, for example?

Saad Usmani, MD: Yes, yes. Generally, the goal is to try to induce cytoreduction fairly quickly, and try to get them to as best a response as you can before taking them to a transplant.

Keith Stewart, MB, CHB: This combination of RVD seems to have become de facto standard, in North America, at least. Is anybody using anything different in their newly-diagnosed patients, outside of trials, just in routine practice?

Paul Richardson, MD: Well, I think in the context of triplets, I completely agree with Saad. The question then becomes the 4-drug regimens and what might you use. And we’ve been participating in a variety of studies—actually in partnership with Sagar—looking at the addition of HDAC (histone deacetylase) inhibitors to the 3-drug platform. For example, now with the approval of panobinostat, there’s the use of panobinostat with RVD after Jatin Shah’s very important work, and prior to that, Sagar and Jonathan’s work with RVD/vorinostat. And we’re comfortable deploying HDAC inhibitors earlier off protocol in patients who we think might be at higher risk.

Keith Stewart, MB, CHB: And there are some new oral drugs that can be considered. I think you’ve got some experience, Amrita, with ixazomib and use with lenalidomide/dexamethasone. Can you speak to that a little bit?

Amrita Krishnan, MD: Certainly. You’re right, oral drugs are very attractive to patients, especially early in the stage of their disease. It’s been well tolerated. For example, the ixazomib/lenalidomide/dexamethasone regimen has induced deep remissions, long responses. I have someone who has been on it for 5 years, right now. Just to Paul’s point though, in terms of additional agents, I do want to mention immunotherapy, as well, in the early upfront setting.

Keith Stewart, MB, CHB: Such as what?

Amrita Krishnan, MD: Well, Saad has a trial, that we participated in, adding elotuzumab to an RVD backbone for high-risk patients. And, certainly, we are opening a trial with the addition of daratumumab to an RVD backbone. So, I think when the immune system is more intact, that is a good time to intervene with these agents.

Keith Stewart, MB, CHB: These are mostly clinical trials at this point, though, that I think is fair to emphasize. Before we leave the triplets, I’m assuming that most people would preserve the all-oral regimen like ixazomib for a more elderly population? We don’t want to neglect that group of patients, so what would you treat an elderly patient with today who came in with newly-diagnosed myeloma?

Sagar Lonial, MD: I think what everybody is summarizing is the idea that an IMiD/PI (proteasome inhibitor) represents probably the best backbone. And, I think, in the United States, the IMiD would be lenalidomide. As for the PI, it really depends.

Transcript Edited for Clarity

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Transcript:

Keith Stewart, MB, CHB:
Let’s move on now. We’ll talk about how we treat newly-diagnosed symptomatic patients. So, these are patients who clearly need therapy. Saad, we’ll start with you. What factors do you consider when determining the most appropriate upfront therapy for your younger transplant-eligible patients?

Saad Usmani, MD: The general approach for the transplant-eligible patients is a triplet regimen across the board.

Keith Stewart, MB, CHB: Triplet of what?

Saad Usmani, MD: Of lenalidomide/bortezomib/dexamethasone (RVD). There are certain situations where you need therapy quickly, for example, a patient who is presenting with renal insufficiency, getting admitted to the hospital, and that’s how they’re being diagnosed. You might reach for a regimen that includes bortezomib/cyclophosphamide/dexamethasone to begin with.

Keith Stewart, MB, CHB: So, patients with renal failure, for example?

Saad Usmani, MD: Yes, yes. Generally, the goal is to try to induce cytoreduction fairly quickly, and try to get them to as best a response as you can before taking them to a transplant.

Keith Stewart, MB, CHB: This combination of RVD seems to have become de facto standard, in North America, at least. Is anybody using anything different in their newly-diagnosed patients, outside of trials, just in routine practice?

Paul Richardson, MD: Well, I think in the context of triplets, I completely agree with Saad. The question then becomes the 4-drug regimens and what might you use. And we’ve been participating in a variety of studies—actually in partnership with Sagar—looking at the addition of HDAC (histone deacetylase) inhibitors to the 3-drug platform. For example, now with the approval of panobinostat, there’s the use of panobinostat with RVD after Jatin Shah’s very important work, and prior to that, Sagar and Jonathan’s work with RVD/vorinostat. And we’re comfortable deploying HDAC inhibitors earlier off protocol in patients who we think might be at higher risk.

Keith Stewart, MB, CHB: And there are some new oral drugs that can be considered. I think you’ve got some experience, Amrita, with ixazomib and use with lenalidomide/dexamethasone. Can you speak to that a little bit?

Amrita Krishnan, MD: Certainly. You’re right, oral drugs are very attractive to patients, especially early in the stage of their disease. It’s been well tolerated. For example, the ixazomib/lenalidomide/dexamethasone regimen has induced deep remissions, long responses. I have someone who has been on it for 5 years, right now. Just to Paul’s point though, in terms of additional agents, I do want to mention immunotherapy, as well, in the early upfront setting.

Keith Stewart, MB, CHB: Such as what?

Amrita Krishnan, MD: Well, Saad has a trial, that we participated in, adding elotuzumab to an RVD backbone for high-risk patients. And, certainly, we are opening a trial with the addition of daratumumab to an RVD backbone. So, I think when the immune system is more intact, that is a good time to intervene with these agents.

Keith Stewart, MB, CHB: These are mostly clinical trials at this point, though, that I think is fair to emphasize. Before we leave the triplets, I’m assuming that most people would preserve the all-oral regimen like ixazomib for a more elderly population? We don’t want to neglect that group of patients, so what would you treat an elderly patient with today who came in with newly-diagnosed myeloma?

Sagar Lonial, MD: I think what everybody is summarizing is the idea that an IMiD/PI (proteasome inhibitor) represents probably the best backbone. And, I think, in the United States, the IMiD would be lenalidomide. As for the PI, it really depends.

Transcript Edited for Clarity
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