Identifying Unmet Clinical Needs in Treating Patients With Extramedullary MM

At the 2024 Lymphoma, Leukemia & Myeloma (LL&M) Congress in New York, New York, Mark Bustoros, MD, Weill Cornell Medicine, New York, New York, shares expert insight into the unmet clinical needs in targeting and treating patients with extramedullary multiple myeloma (MM), an aggressive subtype of myeloma.

Transcript:

Hi, my name is Mark Bustoros. I'm an assistant professor at Weill Cornell Medicine, and I'm here attending the LL&M Congress. Today in the morning we had a session regarding biology and pathology for clinicians.

My talk was about extramedullary myeloma and [the] unmet needs in understanding, at the same time, targeting and treating this aggressive subtype of myeloma. Usually this is a presentation of myeloma where patients would not have the tumor cells just in the bone marrow, but it could be also in other sites of the body, like soft tissues and other organs. [In] my lab, we try to understand how it's different and how we can characterize it.

We used 2 approaches using already available data sets of bone marrow tumor cells and comparing patients who had extramedullary presentations versus the ones who did not. We had another cohort that we developed at [Weill Cornell] and New York-Presbyterian (NYP), where we tried to take the extra tissues, the soft tissues themselves, and sequence them to understand the molecular landscape and compare them to their matching bone marrows. What we've seen [is] that there were some clear differences in terms of the tumor mutation rates and at the same time, the number of copy number alterations and their frequency, which indicate that there is a lot of genomic and chromosome instability in extramedullary myeloma.

We also try to understand what the implications on the tumor microenvironment could be, and how it's different from the standard bone marrow tumor microenvironment. This is work in progress that we are still looking at, but we are seeing some differences. Unfortunately, extramedullary disease with the historical modalities of treatment, but even with the novel immunotherapies have been shown to have worse prognosis and worse outcomes compared to the other myeloma presentations.

We also highlighted some of the previous work that was done in the clinical trials, and a recent study that we've done in the New York Institutes and [in] collaboration with Mount Sinai and Columbia, where we looked at 156 patients who were treated with B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy.

We found 2 interesting observations. One is [regarding] the absolute lymphocyte count in the first 14 days. The maximum value is very predictive of deeper and more durable response. But what we've also seen, and this is real-world data, that the [ ] extramedullary disease, which is basically not attached to the bone, but in the soft tissues, always still does worse.

Even with BCMA CAR T-therapy in this real-world cohort of 156 patients, which again, highlights the need of better understanding and comprehensive kind of understanding of [extramedullary] disease so that we can target it more effectively.

Source:

Bustoros M. Myeloma and the Microenvironment: Comparing Marrow and Extramedullary Disease: Future Directions. Presented at Lymphoma, Leukemia & Myeloma Congress; October 16-19, 2024. New York, NY.