Future of BCMA-Targeted Therapies in Multiple Myeloma

Keith Stewart, MB, ChB: Let’s close with the question of pros and cons of CAR T, antibody-drug conjugates, and BiTEs [bispecific T-cell engagers]. Let’s assume that these are probably going to move earlier in treatment into an early relapsed settings. Why would you choose 1 over the other?

Natalie S. Callander, MD:Well, everybody here probably has the same thoughts, that as these agents get moved up earlier, we’re all very interested to see some of the earlier data, like KarMMa-3, when you are offering CAR [chimeric antigen receptor] T-[cell therapy] after only a couple of therapies. If you start seeing patients and then have durable responses for years, that’s going to be fairly persuasive. The question is whether we’ll be able to do 1 sequential BCMA therapy after another and then what sequence should you do this in.

Keith Stewart, MB, ChB: We’re going to ignore cost right now because, of course, this is not cheap. Noopur, what do you think? Where are we going to use these?

Noopur Raje, MD: I think they’re all going to move earlier and earlier. Some of the things we’ve talked about—in terms of disadvantages of taking 4 to 6 weeks to produce, etc, are going to go away. We are going to be able to do it earlier, without having to worry about things like a bridging therapy. We have to think about sequencing some of these BCMA targets, because 1 of the good things about CAR T cells is it’s 1 and done. If we are able to see a durability of response, in my mind, that’s going to be a huge benefit for our patients. On the other hand, as we bring them earlier, if we don’t see a remission duration that is long lasting, and we’ve got to pull back with some of these other agents, then it’s an open area, and we will be talking about sequencing some of these BCMA-targeted approaches.

Keith Stewart, MB, ChB: Tom, if you had a patient today who had 3 or 4 prior therapies, and if all 3 were available, would you have a preference for antibody-drug conjugate over a BiTE? We’ll take CAR T out of the equation for now.

Thomas G. Martin, MD: The bispecific antibodies are going to be extremely potent for all these patients. It’s going to be moved to front line in early relapse quite quickly. These response rates are 80%, 90%. It’s amazing, actually. I would prefer that bispecific.

Keith Stewart, MB, ChB: Last word to Peter Voorhees.

Peter Voorhees, MD: I agree with Tom in general. For a triple-class refractory patient, if I had the choice between an AC [antibody-drug conjugate] and a bispecific BCMA target, I would lean toward the bispecific. If I had a patient with significant cardiopulmonary disease who I was concerned may not tolerate cytokine release syndrome, I might gravitate toward the antibody-drug conjugate in that scenario. Otherwise, most patients would get the bispecific antibodies. I have a similar level of enthusiasm as Tom does. If the response rates, the durability of those responses are similar to what we’re seeing with CAR T cells, that’s a game changer. Although Noopur is right: Patients enjoy that treatment-free interval. That’s 1 of the most valuable things for them after going through CAR T-cell therapy.

Keith Stewart, MB, ChB: There you have it, folks. Everybody is very excited about BCMA-targeted therapy. We have numerous, probably over a dozen agents in the clinic right now being studied who will probably transform how we treat myeloma. Lots to learn and lots of work to be done to figure out where we’re going to use them most effectively and most cost effectively as well.

I thank the panelists for their time today. It’s been a great discussion. We’ve covered a lot of ground quite quickly. With that, I’d like to thank you all for this, Dr Callander, Dr Martin, Dr Raje, and Dr Voorhees. And thank you to our viewing audience. We hope you found this OncLive® Peer Exchange® discussion to be useful and informative.

Transcription edited for clarity.