The Future of Multiple Myeloma

Yvonne Efebera, MD: What do you see in the future? What do you see as a path to improved outcomes for patients with relapsed/refractory myeloma? I think that’s where we are now.

Thomas Martin, MD:I do want to briefly mention 2 other therapeutics or drugs that I think are going forward. One is selinexor. As we know, selinexor is approved for use, and there were a couple of presentations at American Society of Clinical Oncology (ASCO) virtually. There was the BOSTON trial. It was randomized to selinexor/Velcade/dexamethasone (DEX) versus Velcade/DEX, and an improvement triplet over doublet. There was also a combination of selinexor with daratumumab and a combination of selinexor with carfilzomib. When they’re combined with another drug, it’s given weekly, and I think it’s better tolerated. I’m looking forward to seeing weekly dosing of selinexor with some of these other drugs, to hopefully improve the tolerability of that.

Yvonne Efebera, MD: Yes, and you do give a lot of premedications with the selinexor. We have a cocktail that we give patients.

Thomas Martin, MD: Yes. Then there’s the new cereblon E3 ligase modulators (CELMoDs), the CC-220 and CC-940. I think the CC-220 is iberdomide. Dr Sagar Lonial presented thatat the American Society of Hematology (ASH), showing upwards of a 30% response rate in pomalidomide (POM) failures. Paul Richardson presented data on the most recent CELMoD, what he called CC-940, which had a response rate that was over 50%, which is amazing.He showed some impressive results in the extra-medullary disease. A person had a big liver lesion that disappeared on this combination with dexamethasone.

Those drugs have to move forward, maybe together with some of these immunotherapies, together with bispecifics, together with ADCs (antibody-drug conjugates), maybe with a post-chimeric antigen receptor (CAR) maintenance. The drugs that we have now, 5 years from now… I don’t think we’re going to be using most of them. We’re going to have these novel drugs. That’s what I think we’re moving forward to.

Yvonne Efebera, MD: The CELMoDs—the iberdomide, CC-220—are very tolerable in the phase 1/2 trials. Alliance, now at Cancer Therapy Evaluation Program (CTEP), is looking at combinations in 2 or more prior lines of therapy. It’s really in patients with daratumumab (DARA); it was started also in DARA refractory and then the POM refractory. Which drug has a 30% response rate in DARA refractory patients? It’s nice to have these drugs in clinical trial. Again, after you’ve used all these drugs or in patients who have continued relapse and refractory, for the patients who relapse within 2 years… In all of these treatments, I’m going to put a plug in for allotransplant. These patients are going to relapse, and allotransplant is the only chance for a possible cure in myeloma. Twenty percent of patients may have a cure, but you have to use it early.

A meta-analysis was just published, looking at a 1083 patients that did autologous transplant (auto)-allotransplant (allo) versus auto-auto tandem transplant, and showed that after a median follow-up of 118.5 months, the median overall survival was 98.3 months for the auto-allo compared with 78 patients. The good thing about the allo, if they relapse and are given reinduction and retreatment, myeloma versus disease effect takes over, so the graft-versus-host disease effect also takes over. It showed that patients who relapse after auto-auto or auto-allo did better in terms of progression-free survival (PFS) post-relapse. It was 62.3 months compared with 41.4 months in the tandem transplant.

There’s a clinical trial through the BMT CTN 1302 that closed early because it was a slow accrual, and I think the reason for that is it was initially held off, closed for some toxicity, and then it reopened, which slowed the accrual. After it reopened, we had like 5 patients on that trial. The toxicity was very minimal. We’ve had a few patients who relapsed, and they go back into a complete response (CR) after reinduction of treatment. Allo is an option out there for the young patients, young and … patients who relapse early.

Thomas Martin, MD: Our portfolio of drugs and what we have coming down the pipeline is just tremendous for all of us. We need to devise strategies, a multiprong approach for the newly diagnosed patient, which can really induce a rapid and deep remission; hopefully, it will allow us to step back from the continuous therapy model and be able to take patients off therapy. Maybe there will be a percentage of patients, an increased number of patients, where the myeloma will never come back.

One of our goals should be not only to get to a limited timeframe of therapy—hit people hard and fast for a year, 18 months, or 24 months, and then give them a break—but also to try to get rid of some of our most toxic therapies. I do think that transplant, whether it’s auto or allo, are our most toxic for sure. If we could get rid of those as part of the envelope for frontline therapy and give people longer quality of life, potentially cure 20% or a third or more, that would be the holy grail. That’s what I think we should be going forward with.

Yvonne Efebera, MD: I’m excited about the way things are going in myeloma and to be a part of it. I try to enroll patients in clinical trials, even at first relapse, because that’s the only way we’re going to have more drugs and approve more drugs. Clinical trials are number one for anything. If there aren’t any, then you choose from the others that are available. It’s been a great discussion and I look forward to working with you in the future, Dr Martin. Thank you.

Thomas Martin, MD: Thank you, everyone.

Transcript edited for clarity.