What’s Coming Next in Relapsed/Refractory Multiple Myeloma

James Hoffman, MD: Can you give a brief description of some of the challenges as it relates to the different prognoses for patients with their third relapse, fourth relapse, and fifth relapse and why with those differences—in terms of prognosis over time—it’s so important that we have some of these new options, specifically BCMA-targeted therapies, specifically CAR [chimeric antigen receptor] T-cell therapies and BiTEs [bispecific T-cell engaging antibodies] where you see the field evolving for these patients that have fewer options up to that point.

Joshua Richter, MD: One of the things we see, at least in the United States, is that most patients don’t get beyond third or fourth relapse. Part of that is there’s a subgroup that does so well with the RVD [lenalidomide, bortezomib, dexamethasone] and daratumumab that they die 20 years later of something else. But for the unfortunate people who get to this position where the therapies have taken a toll on their marrow, they’ve taken a toll on their physical and emotional state. It’s not always easy to get levels of drugs into somebody that they can tolerate and that can control the disease. One of the big hopes of BCMA-targeted therapies is that they tend to have a little different adverse-effect profile from some other drugs.

As you said, we’re excited and hopeful about the realm of CAR Ts that we have approved; a number of them are on the way. There are two main classes. One is the bispecifics, of which there are a couple of exciting drugs, both BCMA-based bispecifics like teclistamab and then some other non-BCMA–based bispecifics like talquetamab and cevostamab that target GPRC5D and FCRH5, respectively. The cell mods, the next-generation IMiDs like iberdomide. The big challenge is going to be moving forward. Now that we have even more tools at our disposal, how do we optimally pick them? The way you said at the beginning is perfect. It’s so underestimated how individualized the approach needs to be for a specific patient. The biggest challenge is what to give when. What do you think?

James Hoffman, MD: You summarized that very well. Where are the different BCMA-targeted therapies going to fall out? The bispecifics are off the shelf. The CAR Ts requiring some bridging. [We need to have] some of these immunotherapies that target something other than BCMA, because within a year or 2 we’re all going to have many patients post-BCMA–targeted therapy. That’s going to be a new group of patients with a lot of different needs. The next year or 2 in myeloma is going to be about filling that space with compelling options. Ultimately, we’ll move some of these therapies earlier and aim, as we always do, for cures, which have been elusive, but hopefully we’re on the doorstep of being able to provide them for at least a subset of patients.

Any final things you want to bring up before we summarize and wrap up?

Joshua Richter, MD: No. You said it best in your most recent statement. Cure has been elusive, and there’s probably a small subset that we’re curing accidentally. Hopefully we cure more and more with intention with some of the drugs we have. Other than that, I thank everyone for tuning in.

James Hoffman, MD: It’s been a great pleasure for me. It’s always an opportunity to get to spend time with Dr Richter, a true expert in the field. I always like taking advantage of his wisdom. We were able to run through the landscape of relapse/refractory myeloma. We spent some time reviewing the newest anti-CD38 on the block, isatuximab, trying to figure out where we incorporate that. We talked about the benefits of daratumumab in combination with carfilzomib and the utilization of subcutaneous daratumumab. We spoke a fair amount about BCMA-targeted therapy, both the approved belantamab and the newest CAR T approach, as well as some forward-thinking discussion about bytes and newer CAR Ts to come. We mentioned melphalan as a novel alkylating agent and spent quite a bit of time on selinexor, both its initial approval and even more so in the BOSTON data, specifically highlighting the novel mechanism of action, the more tolerable adverse-effect profile with appropriate supportive care for patients who need a drug that works differently. I remain optimistic about the future for myeloma.

I really thank Dr Richter for his time and appreciate getting to do this with him. I hope that everybody enjoyed and learned something.

TRANSCRIPT EDITED FOR CLARITY