The Potential Impact of Targeting BCMA in R/R Multiple Myeloma - Episode 5

Treatment Options in RRMM

Sagar Lonial, MD, FACP:When you’re trying to decide what to do in the context of a BCMA [B-cell maturation antigen] targeted treatment, some of it will be dependent on what drugs are available, what drugs are approved, and identifying which patients may be better CAR [chimeric antigen receptor] T candidates versus which patients may be better belantamab [mafodotin] candidates is really going to be hard, because we don’t have huge amounts of data for both of them.

I think some of it will be patients that need therapy quickly. The CAR T-cell approach may not necessarily be the optimal option because it takes 4 to 5 weeks for those cells to be made before you can give it back. Meaning belantamab might be a clear option there.

We also know that while CAR T cells are certainly very exciting and show longer progression-free survivals than many other treatments we have available in refractory myeloma, patients may ultimately relapse following CAR T-cell therapy. Having something off the shelf, such as belantamab, might be an exciting option to use in that setting as well.

Choosing treatments based on patient age or demographics right now, I’m not sure we have the data to do that. Patients who are frail may not be able to tolerate the CAR T-cell process. Going preferentially to something that doesn’t have CRS [cardiorenal syndrome] as a potential adverse effect would be an advantage. Not having to give them fludarabine and cyclophosphamide, as you do have to do with a CAR T cell, might be somewhat preferential. Beyond frailty it’s hard to think about ways to discriminate who would get what.

We’re very excited about the next steps in terms of trying to look at which approach for targeting BCMA is best for which patients at which time. There may be a way that we can talk about sequencing—you give one first, you give a second, you give a third after that—but we don’t have enough data on all of these and how prior therapy with BCMA-directed treatments may impact subsequent therapy.

What we do know is that patients don’t really lose expression of BCMA over the course of their disease, and even in patients that relapse post CAR T cell, it’s not because they lose expression of BCMA either, different from what we see with CD19 directed CAR T cells.

The ability to give different ways to approach BCMA to the same patient multiple times makes a lot of sense and may be an approach that we use, particularly in patients that may not be able to wait or may be too frail to get cellular-based therapies at the immediate time point of relapse.

I think the greatest challenge right now is how do we address and minimize the incidence of corneal toxicity in the case of belantamab. How do we address efficacy or lack of efficacy, lack of persistence with CAR T cells and CRS with the bispecific antibodies. Partnering together and figuring out which of those adverse effects and efficacy ratios are best suited for a given patient is something I think we’re going to be working on in the near future.

Transcript edited for clarity.