Novel Developments in the Multiple Myeloma Treatment Landscape

Andrew Yee, MD, Massachusetts General Hospital, Boston, Massachusetts, discusses new developments and possibilities in the treatment landscape for patients with multiple myeloma (MM), including GPRC5D-targeted chimeric antigen receptor (CAR) T-cell therapy, BCL-2-targeting therapy, and the potential for selecting certain regimens for the treatment of patients earlier in the disease course.

Dr Yee discusses these updates at the 2023 Great Debates & Updates in Hematologic Malignancies meeting in Boston, Massachusetts. 

Transcript: 

Hi. Good afternoon, everybody. My name is Andrew Yee. I'm the Clinical Director for the Center for Multiple Myeloma at Mass General Cancer Center. The multiple myeloma landscape is rapidly evolving, and it's a really exciting time for providers in terms of having all these great new drugs available, as well as for patients having more options available. 

It's kind of hard to be like, “Where do you begin?” [Right] off the bat I can think of GPRC5D, which is a new target where we have a new drug that was just approved: talquetamab, which is a bispecific antibody. This is a new cell surface protein, similar to how we have [B-cell maturation antigen] (BCMA) and [cluster of differentiation 38] (CD38). We have this bispecific antibody that's now available for use. 

We also have clinical trials looking at CAR T-cell therapy that targets GPRC5D. It's a whole new branch of multiple myeloma treatment. Other things that are really exciting, as we're talking about CAR T-cells, are trials looking at CAR T-cells, looking at earlier lines of therapy. We already have data looking at the KarMMa-3 study, looking at 2 to 4 prior lines of therapy with [idecabtagene vicleucel] (ide-cel) as well as CARTITUDE-4 which looked at [ciltacabtagene autoleucel] (cilta-cel) in 1 to 3 prior lines of therapy. 

We are hopefully anxiously awaiting for these therapies to be approved in early lines of therapy. Potentially, that could be an option for patients in 2024, since we've seen how transformative CAR T[-cell therapy] has been for patients who've had 4 prior lines of therapy. I think it'll be really exciting to see that option become available for patients earlier in the disease course, rather than waiting later on.

Another exciting development on the horizon would be targeting BCL-2, and we can see how targeting BCL-2 with venetoclax can be really effective in disease with translocation 11;14. There's an ongoing study, the CANOVA study, which will hopefully validate that as a treatment strategy. Other ongoing developments include drugs [that] target cereblon, so already we have drugs such as thalidomide, lenalidomide, and pomalidomide, that would be in the immunomodulatory drug class, which target cereblon. 

We have other drugs that are even more potent than pomalidomide, such as iberdomide and mezigdomide. These drugs are also being evaluated in randomized studies.  These are again, more tools for treating disease and these are being evaluated in combination. These are all the really exciting developments in the myeloma landscape. 

Another target would be [Fc receptor-homolog 5] (FcRH5) and ongoing studies with another bispecific antibody, the cevostamab. Related to the bispecific antibodies would be looking at combinations with these bispecific antibodies as well as evaluating them earlier, in earlier lines of therapy. 

Right now, for example, teclistamab and elranatamab [are] approved in 4 prior lines of therapy. There are ongoing studies right now looking at an earlier disease course of 1 to 3 prior lines and in combination. I think we have all these exciting developments in relapsed disease, and I think what we're looking forward to in the future is to see how we can use these exciting new therapies and apply them earlier in the disease course, where they could potentially be even more beneficial for patients.

Source: 

Yee, A. Making Sense of the Choices in Relapsed Myeloma. Presented at the Great Debates and Updates in Hematologic Malignancies Meeting; August 17-19, 2023; Boston, Massachusetts.