Treating Relapsed Patients with High-Risk Multiple Myeloma, with Dr. Martin

Docwire News spoke with Thomas G. Martin, MD, Professor of Medicine and Associate Director of the Myeloma Program at the University of California, San Francisco, about how he approaches treating a patient with high-risk multiple myeloma (MM) experiencing early relapse.

This is part three of a four-part series featuring Dr. Martin, Watch part one, where he defines high-risk MM, and part two, where he highlights some promising research on improving survival in this patient population.

Docwire News: How do high-risk cytogenetics impact the treatment strategy for MM when dealing with early relapse?

Dr. Martin: I will say two things. The first thing I’ll say in terms of early relapse. My decision on early relapse is much dependent on what I’ve done in frontline therapy. So If I know somebody who has high-risk disease, they’re going to get carfilzomib, lenalidomide, plus dexamethasone (KRd) … and they’re going to get maintenance. And in my mind, the maintenance is going to be a proteasome inhibitor (PI), plus lenalidomide. I do at least a doublet, plus or minus dexamethasone if they can tolerate it. So when they’re relapsing, they’re already relapsing on a PI, lenalidomide plus or minus dexamethasone. So, that’s a tough patient population, I have to think about that.

In my mind, I try to put those patients on a clinical trial, if I have one for those people. But if not, then I will actually choose a triplet regimen and it will include a CD38 antibody. The CD38 antibody, because they haven’t been exposed to CD38. And in the relapse setting, CD38 has been shown to work very well. … And then I choose a partner, so the partner could be carfilzomib (K), in my mind. So right now approved is daratumumab, carfilzomib, and dexamethasone. Or we can choose pomalidomide, so approved is daratumumab, pomalidomide, dexamethasone, but also isatuximab, the other CD38 antibody, pomalidomide and dexamethasone. So I’ll choose between one of those two. And if they, for whatever reason, had intolerance to the bortezomib and I couldn’t keep them on that, and they’ve been off bortezomib then I’ll definitely go with [daratumumab plus carfilzomib and dexamethasone].

If they couldn’t tolerate the [lenalidomide] and they were only on bortezomib, then I will definitely I’ll go to basically isatuximab, pomalidomide, dexamethasone, or daratumumab, pomalidomide, dexamethasone, one of those. … Basically the first out of the gate is a CD38 antibody, plus a next generation PI or an immunomodulatory drug (IMiD).

And so I think those are really good combinations. So, we’re also testing in clinical trials, chimeric antigen receptor (CAR) T cells as part of first to third relapse, and in this setting when they have high-risk disease, I think that actually would be, you give them some induction, you collect their lymphocytes, you give them some bridging therapy, which would be one of those regimens I talked about, and then they get a CAR T. And then we’ll have to see whether maintenance after a CAR T is needed in that scenario.

But I’ll mention one other thing and that is when people relapse, maybe they didn’t have high-risk disease when they first presented. When they relapse, I tend to do a bone marrow biopsy with FISH (fluorescence in situ hybridization) testing at relapse, especially first relapse, especially if it’s a short first relapse. Because I want to see, is this clone that’s driven by one of these high-risk abnormalities?