New Therapeutic Approaches for Multiple Myeloma - Episode 9

Pomalidomide In Lenalidomide-Refractory Multiple Myeloma Patients

Transcript:Keith Stewart, MD, CHB: Bill, a lot of our patients are receiving lenalidomide frontline as maintenance. Would you continue or upregulate the lenalidomide dosing if they’re progressing on maintenance, or what about using pomalidomide in that setting?

William I. Bensinger, MD: Pomalidomide is an important IMiD that was approved a couple of years ago on the basis of some studies in patients who’d received five to six lines of therapy. It’s much more potent an immunomodulatory drug. You’re talking about doses of 2 to 4 mg as opposed to 5 to 25 mg. And it was shown to have single-agent activity in the high teens but when combined with dexamethasone, response rates were in the range of 30%. In addition, when the drug was tested against high-dose dexamethasone, the combination of pomalidomide/dexamethasone resulted in better progression-free survival and better overall survival in that trial.

Keith Stewart, MD, CHB: What do you think? Do you think this is the drug of choice if people relapse on Revlimid?

Jatin P. Shah, MD: Absolutely. I think this is going to be an important backbone for patients who are progressing on Revlimid. And so I think there are different drugs you could add in, and most of us now are not just using pomalidomide/dexamethasone alone. You can for your older frail patients, but I think for more aggressive relapses, carfilzomib/pomalidomide/dexamethasone as we’ve shown is very active and I think one of the most …

Keith Stewart, MD, CHB: Patients in your study were quite heavily pretreated, right?

Jatin P. Shah, MD: Exactly. So, we did a phase I/II study with carfilzomib/pomalidomide/dexamethasone, and those patients were fully refractory; not refractory on 10 mg or maintenance, on 25 mg of lenalidomide/dexamethasone; so, really fully refractory to lenalidomide. And when we did combination of carfilzomib and pomalidomide in that setting, we saw a 70%-plus response rate in that setting. I think it’s a very active combination. You can also add, now that we’re off-label, adding daratumumab to that. Even though there are no data, a combination of daratumumab/pomalidomide/dexamethasone is something that’s going to be an important combination for the future. But I think if you’re looking for data-driven options, pomalidomide/dexamethasone or carfilzomib/pomalidomide/dexamethasone for the Revlimid-refractory patient I think are good options.

Keith Stewart, MD, CHB: I’m struck that pomalidomide, if anything, has less side effects than lenalidomide. But it does seem to cause a bit more myelosuppression. What’s your thought about that, Ola?

C. Ola Landgren, MD, PhD: I have the same experience, it causes more myelosuppression. Many times I go from 4 to maybe 3, or even 2 mg. I have exactly the same experience that Jatin just shared, combining it with carfilzomib and dexamethasone is very powerful in patients who relapse on Revlimid maintenance. And I’ve also used it quite a lot as off label in combination with daratumumab and dexamethasone. It works very, very well.

Keith Stewart, MD, CHB: It seemed to me, I don’t know if it was just me, that it maybe has a little be less fatigue, less diarrhea.

C. Ola Landgren, MD, PhD: It has less of those, absolutely. But myelosuppression is probably the key problem.

Keith Stewart, MD, CHB: I think you really have to be careful when you start combining it with cyclophosphamide or that myelosuppression, neutropenia, is something you have to watch out.

Rafael Fonseca, MD: Speaking of cyclophosphamide, Rachid Baz just had a paper in Blood where they published on cyclophosphamide/pomalidomide/dexamethasone, and actually it’s very, very active. It almost doubles their response rate. So, especially as we’re thinking of those patients who live far away, the elderly, they’re going to be on an all oral regimen, they use 400 mg weekly for cyclophosphamide. But its use increased. And we shouldn’t forget pomalidomide/bortezomib combinations, which there’s been a number of presentations and publications—which is also highly, highly active. I do think it’s the most potent of the IMiDs and it’s just coming in the back end to help us with these combinations.

Keith Stewart, MD, CHB: And yesterday we saw a presentation on even combining with ixazomib or some of these newer drugs.

Jatin P. Shah, MD: Mostly also combine with elotuzumab as well, we talk about different monoclonals. We’ll see some data coming out with pomalidomide plus elotuzumab coming out in the near future as well. I think that will be exciting.

Keith Stewart, MD, CHB: So, it’s a little bit of a backbone in the first relapse setting these days it seems to me. Would you agree?

Jatin P. Shah, MD: I agree.

Transcript Edited for Clarity