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Transplant-Eligible Newly Diagnosed Myeloma

Panelists:Keith Stewart, MD, CHB, Mayo Clinic;William I. Bensinger, MD, Swedish Cancer Institute;Rafael Fonseca, MD, Mayo Clinic;C. Ola Landgren, MD, PhD, Memorial Sloan Kettering Cancer Center;Jatin P. Shah, MD, MD Anderson Cancer Center
Published: Friday, Jul 08, 2016


Transcript:

Keith Stewart, MD, CHB:
All right, so let’s move on. Let’s assume that we have a young patient who needs therapy, Jatin. Now, you’re at MD Anderson. How do you treat a young patient with newly diagnosed myeloma?

Jatin P. Shah, MD: For our newly diagnosed myeloma patients, especially our young patients, we strongly will consider these patients to be transplant-eligible and consider they’re there for their transplant after induction therapy. So, the question really comes to, what is their induction therapy that we use for our newly diagnosed patient that walks into a clinic today? I think, historically, now we’ve seen that the discussion’s always been around two drugs versus three drugs, and which three drugs—being bortezomib plus an alkylating therapy or bortezomib plus an IMiD. I think we have a lot of clarity in the last 12 to 18 months around that.

Now, what we’re seeing consistently is that three drugs is better than two drugs, and we’ve seen this from the SWOG study where we looked at lenalidomide/bortezomib/dexamethasone versus lenalidomide/dexamethasone. We’ve seen this in the relapsed refractory setting from ASPIRE and TOURMALINE, that the combination of three drugs is superior to two drugs.

Keith Stewart, MD, CHB: Tell me about the SWOG study, since you brought this up. This is bortezomib/lenalidomide/dexamethasone versus lenalidomide/dexamethasone alone. What did that teach us?

Jatin P. Shah, MD: It really taught us that, I think, with that three-drug combination, we have higher response rates in these patients. We have a better progression-free survival. But, importantly, we also have improvements in overall survival, as well, which I thought was difficult to prove in a frontline therapy. And I think that was important when we saw an improvement in overall survival with three drugs.

But what that really highlights is one thing that we forget, which is use your best therapies up front. And so, that’s an important oncologic principle: to use your best therapies. I think this really validates that. And if we can stick with that, that will help us understand how to use all of our therapies as we move forward.

Keith Stewart, MD, CHB: It always astonishes me that that’s such a hard message to get across. Does anybody disagree that we should use all our best therapies up front, that we should maybe sequence and save things for later? Is anybody in that camp?

C. Ola Landgren, MD, PhD: Well, I agree. We should use the best drugs up front. And also, I would like to add to that I think it’s equally important to monitor the depth of the response. I think that’s equally important. Not only give the drug, but also to monitor and see how well it really works and see if there is need to improve and change their therapy.

Keith Stewart, MD, CHB: Is bortezomib, dexamethasone alone an adequate therapy or would you consider that inadequate therapy, Bill?

William I. Bensinger, MD: I would echo what’s been said before, that I think there’s clear data that three drugs are superior to two drugs. And so I think in any patient with symptomatic myeloma, and I would include even non-transplant candidates, if they’re fit, a three-drug combination is currently the standard-of-care for these patients. You want a high quality response, and you want it to occur within a few cycles of therapy.

Keith Stewart, MD, CHB: So, within the three drug combinations, we’ve got quite a lot of choices these days. And Rafael, you were one of the early finders of the cyclophosphamide-based combination; we call it CyBorD. Is that something we should still be using, or do you think that there are better choices now?

Rafael Fonseca, MD: There was a trial presented at the ASH meeting with Philippe Moreau, of course, who presented VTD (bortezomib-thalidomide-dexamethasone) versus VCD (bortezomib-cyclophosphamide-dexamethasone). So, let’s say V-IMiD-dexamethasone versus cyclophosphamide combinations. I think, in general, we’re learning that IMiD-based combinations are better, and triplets. The only comment—and this is more for if there’s anyone from the international audience—I think a cyclophosphamide combination is still highly effective. In that particular study, there were only 2 days of overlap of bortezomib with a cyclophosphamide, which is not really how we practice a CyBorD.

But I’ll just second what everyone has been saying. I think the triplet combinations are really the standard. And, in fact, the numbers don’t matter as much as the components because very quickly we’re going to be facing monoclonals plus, and we’re going to talk more about that. But I think everything we’re discussing today is only temporary, given what’s being presented at the ASCO meeting.

Keith Stewart, MD, CHB: I was saying to Bill earlier that one of the issues with the cyclophosphamide combinations is we’ve watered it down so much by going from twice-weekly bortezomib, to once-weekly high-dose dexamethasone, to low-dose dexamethasone, and it’s not quite what we originally published. What about ixazomib? This is a new oral proteasome inhibitor that’s been combined in the frontline setting. What do you think as a choice?

C. Ola Landgren, MD, PhD: Well, it’s not yet approved for the up-front indication, obviously. I think the data looks, to me, very attractive for the relapse data that we have heard at meetings, and has been published also this year. I think it looks like an equivalent of Velcade, but you have the convenience factor of an oral therapy. I personally do think that for a younger patient, my preference would be to probably give Kyprolis because I think there is more power in that drug. But I think there could be very many instances where you still could use the oral drug just for the convenience. So, I think both those drugs are very good options, and different patients would have access to these.

Transcript Edited for Clarity
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Transcript:

Keith Stewart, MD, CHB:
All right, so let’s move on. Let’s assume that we have a young patient who needs therapy, Jatin. Now, you’re at MD Anderson. How do you treat a young patient with newly diagnosed myeloma?

Jatin P. Shah, MD: For our newly diagnosed myeloma patients, especially our young patients, we strongly will consider these patients to be transplant-eligible and consider they’re there for their transplant after induction therapy. So, the question really comes to, what is their induction therapy that we use for our newly diagnosed patient that walks into a clinic today? I think, historically, now we’ve seen that the discussion’s always been around two drugs versus three drugs, and which three drugs—being bortezomib plus an alkylating therapy or bortezomib plus an IMiD. I think we have a lot of clarity in the last 12 to 18 months around that.

Now, what we’re seeing consistently is that three drugs is better than two drugs, and we’ve seen this from the SWOG study where we looked at lenalidomide/bortezomib/dexamethasone versus lenalidomide/dexamethasone. We’ve seen this in the relapsed refractory setting from ASPIRE and TOURMALINE, that the combination of three drugs is superior to two drugs.

Keith Stewart, MD, CHB: Tell me about the SWOG study, since you brought this up. This is bortezomib/lenalidomide/dexamethasone versus lenalidomide/dexamethasone alone. What did that teach us?

Jatin P. Shah, MD: It really taught us that, I think, with that three-drug combination, we have higher response rates in these patients. We have a better progression-free survival. But, importantly, we also have improvements in overall survival, as well, which I thought was difficult to prove in a frontline therapy. And I think that was important when we saw an improvement in overall survival with three drugs.

But what that really highlights is one thing that we forget, which is use your best therapies up front. And so, that’s an important oncologic principle: to use your best therapies. I think this really validates that. And if we can stick with that, that will help us understand how to use all of our therapies as we move forward.

Keith Stewart, MD, CHB: It always astonishes me that that’s such a hard message to get across. Does anybody disagree that we should use all our best therapies up front, that we should maybe sequence and save things for later? Is anybody in that camp?

C. Ola Landgren, MD, PhD: Well, I agree. We should use the best drugs up front. And also, I would like to add to that I think it’s equally important to monitor the depth of the response. I think that’s equally important. Not only give the drug, but also to monitor and see how well it really works and see if there is need to improve and change their therapy.

Keith Stewart, MD, CHB: Is bortezomib, dexamethasone alone an adequate therapy or would you consider that inadequate therapy, Bill?

William I. Bensinger, MD: I would echo what’s been said before, that I think there’s clear data that three drugs are superior to two drugs. And so I think in any patient with symptomatic myeloma, and I would include even non-transplant candidates, if they’re fit, a three-drug combination is currently the standard-of-care for these patients. You want a high quality response, and you want it to occur within a few cycles of therapy.

Keith Stewart, MD, CHB: So, within the three drug combinations, we’ve got quite a lot of choices these days. And Rafael, you were one of the early finders of the cyclophosphamide-based combination; we call it CyBorD. Is that something we should still be using, or do you think that there are better choices now?

Rafael Fonseca, MD: There was a trial presented at the ASH meeting with Philippe Moreau, of course, who presented VTD (bortezomib-thalidomide-dexamethasone) versus VCD (bortezomib-cyclophosphamide-dexamethasone). So, let’s say V-IMiD-dexamethasone versus cyclophosphamide combinations. I think, in general, we’re learning that IMiD-based combinations are better, and triplets. The only comment—and this is more for if there’s anyone from the international audience—I think a cyclophosphamide combination is still highly effective. In that particular study, there were only 2 days of overlap of bortezomib with a cyclophosphamide, which is not really how we practice a CyBorD.

But I’ll just second what everyone has been saying. I think the triplet combinations are really the standard. And, in fact, the numbers don’t matter as much as the components because very quickly we’re going to be facing monoclonals plus, and we’re going to talk more about that. But I think everything we’re discussing today is only temporary, given what’s being presented at the ASCO meeting.

Keith Stewart, MD, CHB: I was saying to Bill earlier that one of the issues with the cyclophosphamide combinations is we’ve watered it down so much by going from twice-weekly bortezomib, to once-weekly high-dose dexamethasone, to low-dose dexamethasone, and it’s not quite what we originally published. What about ixazomib? This is a new oral proteasome inhibitor that’s been combined in the frontline setting. What do you think as a choice?

C. Ola Landgren, MD, PhD: Well, it’s not yet approved for the up-front indication, obviously. I think the data looks, to me, very attractive for the relapse data that we have heard at meetings, and has been published also this year. I think it looks like an equivalent of Velcade, but you have the convenience factor of an oral therapy. I personally do think that for a younger patient, my preference would be to probably give Kyprolis because I think there is more power in that drug. But I think there could be very many instances where you still could use the oral drug just for the convenience. So, I think both those drugs are very good options, and different patients would have access to these.

Transcript Edited for Clarity
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