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Role of Maintenance Therapy in Myeloma

Panelists: A. Keith Stewart, MB, ChB, The Mayo Clinic in Phoenix Arizona; Thomas Martin, MD, UCSF Helen Diller Family Comprehensive Cancer Center; Faith Davies, MD, MBBCh, MRCP, FRCPath, University of Arkansas for Medical Sciences; Rafael Fonseca, MD, The Mayo Clinic in Phoenix Arizona; Adriana Rossi, MD, Weill Cornell Medical College
Published: Wednesday, Feb 13, 2019



Transcript:

A. Keith Stewart, MB, ChB:
What about, to wrap this up, can you provide just 1 sentence on maintenance? I think we’ve all concluded that maintenance is good and most people should be on it. The only controversy left, it seems to me, is stopping over time or indefinitely. I hate the idea that you have a patient on this for a decade who might be cured, for example. How are we going to deal with that, Tom?   

Thomas Martin, MD: Well, I think at this ASH [American Society of Hematology annual meeting] there were a couple of presentations on using ixazomib, an oral proteasome inhibitor [PI], as a maintenance-based strategy. I think there was an instance where they used ixazomib as maintenance in the nontransplant setting. And there really didn’t seem to be a benefit of ixazomib maintenance. And then Dr Meletios Dimopoulos presented it in a post-transplant setting. So any induction, single autologous transplant and then ixazomib maintenance for 2 years. And the ixazomib maintenance arm had a PFS [progression-free survival] of 26 months and the placebo-based maintenance had a PFS of 21 months. So it was significantly improved but comparing apples to oranges, and we always do that, unfortunately, compared to lenalidomide it seemed like it didn’t have as much strength. So if I’m going to use a 1-drug maintenance therapy, I’m going to probably use lenalidomide.

A. Keith Stewart, MB, ChB: Let’s get some other opinions. But the TOURMALINE study, which was ixazomib versus placebo, a big phase III trial, 4-month improved PFS at the cost of some toxicity.

Adriana Rossi, MD: I think my biggest issue with that is that in my definition of maintenance, maintenance is one of the agents that got you to that response being used to maintain that response. And these patients had other inductions, transplant and then were started on ixazomib as a new line of therapy. Really, calling it maintenance to me is semantics, but to me that is not maintenance. I do believe in keeping them on, and I generally do go down to a single drug. I try to get patients off steroids, the sooner the better.

A. Keith Stewart, MB, ChB: Well, let’s assume we get everybody off steroids. But I guess what the question becomes, since there was some benefit for ixazomib, is it ixazomib plus lenalidomide now?

Faith Davies, MD, MBBCh, MRCP, FRCPath: I’m going to correct you. I think it was a 6-month benefit.  I think the other thing that you were talking about earlier, and I think Rafael mentioned it as well, is that I’m not sure that 2 years is enough because in the initial French study, you see people drop off the curve as soon as the drug stopped.

A. Keith Stewart, MB, ChB: And you saw that in the UK [United Kingdom] as well.

Faith Davies, MD, MBBCh, MRCP, FRCPath: And we saw it in the UK, and I think we see it here as well.

A. Keith Stewart, MB, ChB: Is it forever?

Faith Davies, MD, MBBCh, MRCP, FRCPath: I’m not sure it’s forever either, OK? I agree with that one. But I think that maybe we do need 3 years. I think the other thing is, as you said, what this does is give us confidence regarding whether it’s tolerable, and if we want to actually add it to Revlimid, and we can argue whether we’re now getting into long consolidation or not, but you know it’s certainly a regimen that’s oral, tolerable, and you can….

A. Keith Stewart, MB, ChB: Let’s do a little rapid fire here. What about other drugs in maintenance, daratumumab?

Rafael Fonseca, MD: OK, so there’s my fourth point on maintenance. Well, daratumumab was my fourth. Everybody should get maintenance unless there’s a compelling reason not to. High risk: combined PI plus lenalidomide. That’s what I’m doing and I use ixazomib for that. I predict we’re going….

A. Keith Stewart, MB, ChB: Let me stop you. Why would you use that in standard risk as well?

Rafael Fonseca, MD: I think the data for standard risk are good enough that I would say it’s contingent upon other trials to show me that you can do better with that. That’s a good question. There’s no way to rebut that categorically. But here are 2 things more for other drugs. I think we should start preparing for seeing venetoclax for 11;14 [translocation] maintenance. And the last point I think, MRD [minimal residual disease] will be key in how we manage maintenance. Instead of guessing 2 years, 3 years, you know you have to sustain MRD-negative status, then you’re okay.

A. Keith Stewart, MB, ChB: Tom?

Thomas Martin, MD: I think daratumumab is going to really be the agent that we’re going to use, likely together with either pomalidomide, or if they’re high risk, or if they have residual disease; or with lenalidomide, if they just have standard risk. I think it’s going to be a 2-drug regimen with an antibody going forward.

A. Keith Stewart, MB, ChB: It kind of feels to me like that’s where we’re heading. You’ll get your remission and then you’ll probably have 2- or 3-drug maintenance of some kind. I hate to think about the cost so we’re not going to go there. But it’s a significant….

Adriana Rossi, MD: It would be nice to be able to identify which patients need it and which patients need the PI or….

A. Keith Stewart, MB, ChB: Maybe in the next section we’ll find ways we can avoid it, right?

Transcript edited for clarity.

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Transcript:

A. Keith Stewart, MB, ChB:
What about, to wrap this up, can you provide just 1 sentence on maintenance? I think we’ve all concluded that maintenance is good and most people should be on it. The only controversy left, it seems to me, is stopping over time or indefinitely. I hate the idea that you have a patient on this for a decade who might be cured, for example. How are we going to deal with that, Tom?   

Thomas Martin, MD: Well, I think at this ASH [American Society of Hematology annual meeting] there were a couple of presentations on using ixazomib, an oral proteasome inhibitor [PI], as a maintenance-based strategy. I think there was an instance where they used ixazomib as maintenance in the nontransplant setting. And there really didn’t seem to be a benefit of ixazomib maintenance. And then Dr Meletios Dimopoulos presented it in a post-transplant setting. So any induction, single autologous transplant and then ixazomib maintenance for 2 years. And the ixazomib maintenance arm had a PFS [progression-free survival] of 26 months and the placebo-based maintenance had a PFS of 21 months. So it was significantly improved but comparing apples to oranges, and we always do that, unfortunately, compared to lenalidomide it seemed like it didn’t have as much strength. So if I’m going to use a 1-drug maintenance therapy, I’m going to probably use lenalidomide.

A. Keith Stewart, MB, ChB: Let’s get some other opinions. But the TOURMALINE study, which was ixazomib versus placebo, a big phase III trial, 4-month improved PFS at the cost of some toxicity.

Adriana Rossi, MD: I think my biggest issue with that is that in my definition of maintenance, maintenance is one of the agents that got you to that response being used to maintain that response. And these patients had other inductions, transplant and then were started on ixazomib as a new line of therapy. Really, calling it maintenance to me is semantics, but to me that is not maintenance. I do believe in keeping them on, and I generally do go down to a single drug. I try to get patients off steroids, the sooner the better.

A. Keith Stewart, MB, ChB: Well, let’s assume we get everybody off steroids. But I guess what the question becomes, since there was some benefit for ixazomib, is it ixazomib plus lenalidomide now?

Faith Davies, MD, MBBCh, MRCP, FRCPath: I’m going to correct you. I think it was a 6-month benefit.  I think the other thing that you were talking about earlier, and I think Rafael mentioned it as well, is that I’m not sure that 2 years is enough because in the initial French study, you see people drop off the curve as soon as the drug stopped.

A. Keith Stewart, MB, ChB: And you saw that in the UK [United Kingdom] as well.

Faith Davies, MD, MBBCh, MRCP, FRCPath: And we saw it in the UK, and I think we see it here as well.

A. Keith Stewart, MB, ChB: Is it forever?

Faith Davies, MD, MBBCh, MRCP, FRCPath: I’m not sure it’s forever either, OK? I agree with that one. But I think that maybe we do need 3 years. I think the other thing is, as you said, what this does is give us confidence regarding whether it’s tolerable, and if we want to actually add it to Revlimid, and we can argue whether we’re now getting into long consolidation or not, but you know it’s certainly a regimen that’s oral, tolerable, and you can….

A. Keith Stewart, MB, ChB: Let’s do a little rapid fire here. What about other drugs in maintenance, daratumumab?

Rafael Fonseca, MD: OK, so there’s my fourth point on maintenance. Well, daratumumab was my fourth. Everybody should get maintenance unless there’s a compelling reason not to. High risk: combined PI plus lenalidomide. That’s what I’m doing and I use ixazomib for that. I predict we’re going….

A. Keith Stewart, MB, ChB: Let me stop you. Why would you use that in standard risk as well?

Rafael Fonseca, MD: I think the data for standard risk are good enough that I would say it’s contingent upon other trials to show me that you can do better with that. That’s a good question. There’s no way to rebut that categorically. But here are 2 things more for other drugs. I think we should start preparing for seeing venetoclax for 11;14 [translocation] maintenance. And the last point I think, MRD [minimal residual disease] will be key in how we manage maintenance. Instead of guessing 2 years, 3 years, you know you have to sustain MRD-negative status, then you’re okay.

A. Keith Stewart, MB, ChB: Tom?

Thomas Martin, MD: I think daratumumab is going to really be the agent that we’re going to use, likely together with either pomalidomide, or if they’re high risk, or if they have residual disease; or with lenalidomide, if they just have standard risk. I think it’s going to be a 2-drug regimen with an antibody going forward.

A. Keith Stewart, MB, ChB: It kind of feels to me like that’s where we’re heading. You’ll get your remission and then you’ll probably have 2- or 3-drug maintenance of some kind. I hate to think about the cost so we’re not going to go there. But it’s a significant….

Adriana Rossi, MD: It would be nice to be able to identify which patients need it and which patients need the PI or….

A. Keith Stewart, MB, ChB: Maybe in the next section we’ll find ways we can avoid it, right?

Transcript edited for clarity.
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