Switching IMiDs: The OPTIMISMM Trial's Impact on MM

Transcript:

A. Keith Stewart, MB, ChB: We heard from Dr. Richardson yesterday about the OPTIMISMM study. This compared pomalidomide/bortezomib/dexamethasone with the control arm of bortezomib/dexamethasone alone. Amrita, what did you think of that presentation? Will it change our practice or was it kind of expected results?

Amrita Krishnan, MD, FACP: It was expected but maybe it will change my practice a little bit more than I expected it to as well.

A. Keith Stewart, MB, ChB: Why is that?

Amrita Krishnan, MD, FACP: So, 60% of the patients did have prior bortezomib. Obviously, there were actually about 6% who were bortezomib-refractory, but I exclude those and really looked at the other ones that had prior exposure. The patient you described—RVd, transplant, lenalidomide maintenance—you could actually consider pomalidomide/Velcade/dexamethasone for that group of patients. They should do fairly well and it’s a well-tolerated regimen.

A. Keith Stewart, MB, ChB: I think one of the keys I took away from the presentation was that they enrolled a lot of Revlimid-refractory patients. Is that your understanding, too?

Sagar Lonial, MD, FACP: Two-thirds.

A. Keith Stewart, MB, ChB: And Sagar, does it make you feel more comfortable using pomalidomide as opposed to a non-IMiD regimen?

Sagar Lonial, MD, FACP: Yes. I think it sort of now gives us another alternative with phase III data as a pomalidomide-based salvage regimen. And I think not only does it sort of give credence to BVD, but I think it also gives credence to the idea of pomalidomide plus ixazomib, as Amrita has shown as another alternative for an all oral salvage regimen.

Ajai Chari, MD: And also, I think what’s probably unique about the study is the movement of pomalidomide to earlier lines of therapy. So, if you’re practicing on-label, it’s not given in first relapse. And so, here, the first relapse is allowed. So, I think it shows that if pomalidomide was earlier, you do see a better mileage from the drug.

Edward A. Stadtmauer, MD: There’s also something very comfortable for the patients to just switch to lenalidomide to pomalidomide. It’s just taking another pill and they usually can…

A. Keith Stewart, MB, ChB: Are you convinced that you can rescue lenalidomide-refractory patients with pomalidomide alone, or do you need to use triplet therapy? And if so, what’s the contribution of pomalidomide then?

Sagar Lonial, MD, FACP: I think you can. I think the durability of that response is much better in a triplet than it is with just pomalidomide/dexamethasone alone.

A. Keith Stewart, MB, ChB: What’s the biologic rationale for that? You’ve got the same class of drugs targeting the same protein. Why do you think going from one to the other would be an effective strategy?

Sagar Lonial, MD, FACP: Well, I think there are differences in potency and binding affinities. I think your lab has actually shown differences in what the downstream effects of lenalidomide versus pomalidomide versus now CC-220 and other compounds in that same category are. So, there are probably subtle differences between the drugs.

Edward A. Stadtmauer, MD: And it works. In clinical practice, we’ve done this and we’ve seen patients who’ve had nice responses.

A. Keith Stewart, MB, ChB: Fair enough.

Thomas Martin, MD: I was really surprised. I’m wondering what you guys think. In the Revlimid-refractory population, the PFS was actually only 9 months. And that’s actually a theme from almost all the studies that were presented yesterday, that the PFS, and when somebody becomes lenalidomide-refractory, it’s actually typically less than a year.

A. Keith Stewart, MB, ChB: Yes, but in first relapse, it was 20.

Thomas Martin, MD: That was first relapse. But if you just took the lenalidomide-refractory patients, the PFS was 9 months. And then Ajai presented data, too, with carfilzomib and daratumumab in the lenalidomide-refractory, and the PFS was the best, it was 14 months. But once you become lenalidomide-refractory, your PFS actually is not so good. It’s actually really, I think, obviously a bad prognostic marker, even with pomalidomide and bortezomib, etc.

A. Keith Stewart, MB, ChB: Watch, you’re throwing out one of your major drug classes that becomes difficult. One of the things I took away was that if you’re going to use these triplet regimens, it should be at first relapse because the 20-month PFS for the triplet was, I thought, quite impressive.

Ajai Chari, MD: Very nice.

Transcript Edited for Clarity