Emerging Therapies in RRMM

Kenneth Shain, MD, PhD: Phase 3 data are driving new options in early relapse disease with monoclonal antibodies incorporated into triplet therapy. We talked a lot about the novel therapy melphalan flufenamide in late-relapse patients, the pluses and minuses of that, and the success that we hope can carry forward. We want to make sure we’re always thinking about other approved agents as well. Belantamab mafodotin is another agent that was recently approved for late-relapse therapy. BCMA [B-cell mutation antigen] targeting antibody-drug conjugate. Selinexor has been around for a while to treat those late-relapse patients as we learn that more combinations are available. Depending on how those data roll out, we can use selinexor in different combinations with bortezomib, selinexor, and dexamethasone, or soon-to-be other standard myeloma therapies in combination with selinexor. That’s an important thing for our patients. It’s a novel mechanism of action.

We need to take a step back and a step sideways. There’s a new group of agents or targeted ways of thinking about things in myeloma, like immunotherapies. When I say immunotherapies, I don’t mean the successful and incredibly important IMiDs [immunomodulatory imide drugs] and monoclonal antibodies. I mean these T-cell engaging direct or indirect T-cell engaging modalities. One is cellular, and 1 is noncellular. CAR [chimeric antigen receptor] T cells are an incredibly new and novel way of targeting myeloma cells and reducing disease burden in ways we’ve never seen before, even in late-late relapse patients. Response rate is between 73% and 95% in late-late relapse patients. Progression-free survival is from 7 to 20 months.

We now have approval with Abecma, or idecabtagene vicleucel, from BMS [Bristol Myers Squibb]. That’s an incredibly important new therapy. Hopefully, another new CAR T-cell product will be approved in the not-too-distant future, which will give more options for our patients and be more available to our patients in that setting. BCMA-targeting CAR T cells will be a very important part of our momentum moving forward. Lastly, we don’t want to forget about the direct bispecific T-cell engagers [BiTEs] out there. These are either pieces of antibodies or the antibodies themselves that are able to directly drag CD3-positive T cells to targets. Most of those are BCMA, but other new targets are being evaluated as well. These are all things that we know are being looked at in multiple clinical trials. There are some outstanding response rates and outstanding ways to think about things in patients with late-late relapse disease, where we’re seeing minimal residual disease, negative disease. We’re seeing great responses in places that we wouldn’t typically see it.

We need to harness our own immune system, whether it’s creating T cells that can be put into patients to target the myeloma and CAR T or utilizing the T cells in the marrow by using BiTEs or second and third generations of these. They might bring in more than 1 product or other cellular immune components that are important next steps for us. We have to be excited about the future from an immunotherapies perspective. We have a lot of new agents approved to help.

One group of agents I want to make sure we’re thinking about are CELMoDs [cereblon E3 ligase modulators], the next-generation immunomodulatory drugs. Iberdomide and a more recent 1, CC-92480, have been looked at in studies and are being looked at in combination studies that are effective even in late relapse. This is another group that will hopefully help us continue to change and evolve the landscape of treatment for myeloma patients. It’s an amazing and exciting time for how we can balance new immunotherapeutic-targeting agents, new generations of immunotherapy, and more traditional therapies that target myelobiology. There’s a lot more work to do to figure out how we use these them best and how we strategize around sequencing and personalizing therapy for our patients. Can we use patient attributes? Can we use disease attributes to help target better populations that may be more affected by 1 set of drugs vs another? If you hear enough of the drugs and the combinations of the new products we’ve talked about, you can get a feel for how exciting it is in terms of how we can help improve outcomes for all our patients. It’s an exciting time, and we keep pushing the limit as best we can and continue to push to that ultimate goal of taking care of our patients.

Transcript edited for clarity.