Therapy Based on Rapid versus Slow Progression of Myeloma

Transcript:Keith Stewart, MD, CHB: Despite our best intentions, most myeloma patients relapse. So, let’s turn our attention now to the relapse setting. We have a plethora of new drugs approved, and we need to help people understand when to use these and when not to use these. NCCN has eight different potential therapies to use with relapse. Let’s work on the hypothesis that our patient has had bortezomib, lenalidomide, dexamethasone; a transplant; and lenalidomide maintenance; and is now relapsing for the first time. Rafael, how would you treat that patient?

Rafael Fonseca, MD: Well, I think I would go back to my previous point. I would want to see which type of relapse we’re experiencing and also the risk category. The patient, for all-comers, right now, if I had to say everything else being the same, my number-one approach has been carfilzomib, lenalidomide, and dexamethasone for first relapse.

Keith Stewart, MD, CHB: Even if they’ve been on lenalidomide maintenance?

Rafael Fonseca, MD: For sure.

Keith Stewart, MD, CHB: You would switch to pomalidomide?

Rafael Fonseca, MD: Yes. The intent of your first wave of treatment, if you mean when you get to transplant, is to get the patient into that CR and, hopefully, to a cure. I know there are data that’s shown very long duration of response in some patients. I think that intent remains for the first relapse based on the data of a CR of 30% in the ASPIRE data. Now, again, this is temporary. We’ll see what monoclonals play in the next wave of clinical trials.

Keith Stewart, MD, CHB: Does the speed of relapse matter? We know about genetic risk. What about the tempo of relapse, aggressive versus nonaggressive? Does that matter to you, Ola?

C. Ola Landgren, MD, PhD: I think this is another big question. We all know that there are many types of relapses. You have the slow indolent relapses; you have these aggressive relapses. I think we probably all agree that for the aggressive ones, we need to have powerful therapy. But for the indolent ones, I think you could basically ask the same question as when we started off talking about lenalidomide to start therapy at all in the smoldering, or do you need to have symptoms?

Keith Stewart, MD, CHB: Do you wait and watch then, or do you, as soon as you see the protein going up, start a treatment?

C. Ola Landgren, MD, PhD: So, what I was trying to say is that for that indolent relapse, I think one approach is to wait and to go in with more indolent therapy. You could have oral therapy; you could increase Revlimid. You could go up to 25 mg of lenalidomide if you were on maintenance and add dexamethasone. In my experience, it doesn’t usually work, and it doesn’t work for a long time.

Keith Stewart, MD, CHB: I’ve had no luck with that either.

C. Ola Landgren, MD, PhD: I think adding, for example, carfilzomib, is a very powerful approach. Now, there are new other drugs that are available—ixazomib, daratumumab will be another option, and elotuzumab, etc.

Keith Stewart, MD, CHB: So, you’re a practicing community physician, let’s just assume. I’ll turn to this side of the table for a minute; this is a fairly rapid relapse. M protein’s really not fast, and the patient’s getting some symptoms. Bill, what do you use in this setting?

William I. Bensinger, MD: Well, if I have someone as you’ve described, who’s been on lenalidomide and is failing rapidly and explosively, I would probably go to a triplet of carfilzomib, pomalidomide, and dexamethasone. That’s been shown to have a very high response rate. In fact, Jatin conducted the first trial with this combination, and it was highly effective.

Keith Stewart, MD, CHB: Jatin, what if it was a slower indolent relapse? What would you do?

Jatin P. Shah, MD: I think there’s a unique opportunity in that setting to incorporate elotuzumab. And I think one of the nice things that we see.

Keith Stewart, MD, CHB: What is elotuzumab, for in case someone listening doesn’t know about that?

Jatin P. Shah, MD: A great question. This is another, one of the new monoclonal antibodies that targets SLAMF7, which is expressed on plasma cells, as well as NK (natural killer) cells. And so, one of the exciting things about that is potentially with this kind of immune-stimulating component: the NK cells can get potentially long-term disease control. The perfect candidate, I think, would be those patients that are biochemically slow-progressing, to add in lenalidomide/dexamethasone/elotuzumab because when you start thinking about it, you want to maximally leverage each one of the therapies that we have. And if you want to maximally leverage elotuzumab, that is the ideal setting. You’re going to really leverage the benefit, not that aggressive relapse.

Keith Stewart, MD, CHB: Even if they’re young, a young patient with an indolent relapse, you would think elotuzumab would be your choice, as opposed to carfilzomib, for example?

Jatin P. Shah, MD: I think carfilzomib is still a good option. But for the biochemically slow progressors without that rapid progression, a doubling of the M protein in the next month for that patient because when else are you going to use elotuzumab? Again, trying to harness when I am going to use each one of the therapies.

Keith Stewart, MD, CHB: One of the challenges I run into in my own practice is that the insurance companies have been quite strict about having to use elotuzumab with lenalidomide, and these are patients who have been on lenalidomide recently and are progressing. We have found that a bit challenging, then, to work that drug in in the younger patient at least.

Jatin P. Shah, MD: If they’re rapidly progressing, yes. But if they’re slowly biochemically progressing just on single-agent lenalidomide, I think, for some of those patients, you’re right. For a lenalidomide-refractory patient, you don’t want to use lenalidomide/dexamethasone/elotuzumab. But for potentially those patients who are progressing on low-dose 5 mg or 10 mg very slowly, that might be a unique opportunity.

Keith Stewart, MD, CHB: What about pomalidomide with elotuzumab? Are there any data on that?

Jatin P. Shah, MD: I don’t think there are any data now in terms of pomalidomide plus elotuzumab. I think, biologically, it would make sense, but it’s important to have those data. And I agree with you—what Bill was saying—for a more aggressive relapse, I think carfilzomib-based therapy is going to be important. Either carfilzomib with lenalidomide/dexamethasone or carfilzomib with pomalidomide/dexamethasone.

Transcript Edited for Clarity