Monoclonal Antibodies in Relapsed-Refractory 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
A. Keith Stewart, MB, ChB: Let me come back now to monoclonal antibodies. We’ve talked a little bit about daratumumab, which has really found its home in first relapse in the United States. There was a study presented here [at the American Society of Hematology Annual Meeting and Exposition] that looked at outcomes in people who had previously received lenalidomide and then were going to get lenalidomide and dexamethasone at relapse. Does it worry you? Would you ever use lenalidomide, or are you going straight to pom [pomalidomide]?
Thomas Martin, MD: My personal practice is that I do go to pom, because if they’re lenalidomide-refractory, I figure there’s going to be a better response rate. However, the addition of the IMiD [immunomodulatory drug] is really to get that pro IL-2 [interleukin-2] effect. Both drugs will do it, but I just think you’ll have a better and a longer response if you switch to the more potent IMiD.
A. Keith Stewart, MB, ChB: What about elotuzumab? You mentioned this already, Tom, but what do you think about that, Dr Rossi?
Adriana Rossi, MD: It’s tough when you have 2 monoclonals.
A. Keith Stewart, MB, ChB: This is the OPTIMISMM trial, is that correct? Am I getting the right trial?
Thomas Martin, MD: ELOQUENT-3.
Adriana Rossi, MD: With elotuzumab, pomalidomide, and dex [dexamethasone].
A. Keith Stewart, MB, ChB: That’s ELOQUENT-3? OK. Keep me straight.
Adriana Rossi, MD: There’s so much data. It’s another good problem to have.
A. Keith Stewart, MB, ChB: So what did you think of that? It was published in the New England Journal of Medicine last month.
Adriana Rossi, MD: Yes. Again, it’s a good combination. I think daratumumab sort of becomes everyone’s favorite monoclonal, but we have to remember that we do have an option, and if we are moving daratumumab up front—having, say, a dara-Rd up front—then the elotuzumab/pomalidomide allows for a completely new triplet.
A. Keith Stewart, MB, ChB: Is there daratumumab resistance, Faith? Can you retreat with daratumumab?
Faith Davies, MD, MBBCh, MRCP, FRCPath: Yes, you can definitely retreat with daratumumab.
A. Keith Stewart, MB, ChB: Do you think it works even if you failed with it before?
Faith Davies, MD, MBBCh, MRCP, FRCPath: Yeah. I think that, as with all drugs, there are nuances as to how long and what the amount of space you need between weekly is, and so on. But yeah, I’ve had plenty of experience at having good response rates.
A. Keith Stewart, MB, ChB: And I was struck by our lymphoma colleagues who just use rituximab everywhere, even if they’ve had it before and progressed. But Rafael, are you seeing any daratumumab resistance?
Rafael Fonseca, MD: Clinically you can see it, and particularly I think when you run into trouble with the combinations, but even with the combinations, you do see resistance. So I have patients who responded for some time to daratumumab, pomalidomide, dexamethasone and then progressed through that. So we do see that. I think your point is well taken. Of course, we’re going to have other antibodies too, and other CD38s were presented at this meeting.
A. Keith Stewart, MB, ChB: What about elotuzumab in those patients who you’re seeing resistance in? Is this something you’re excited about?
Rafael Fonseca, MD: That’s a very important question. The New England Journal of Medicine paper does show a nearly doubling of the response rate—you know, PFS [progression-free survival]. However, only a very small fraction of those patients had daratumumab exposure. I believe it’s in the range of 2%. That’s a critical question. Now, pomalidomide works well, but pomalidomide has to be combined, and particularly in that setting. So there’s a previous study in combination with cyclophosphamide from Moffitt [Cancer Center]. This is the OPTIMISMM study in combination with bortezomib. But we need to have that option for patients who are relapsing after standard second-line therapy.