COMy 2025 | Challenges and opportunities in extramedullary myeloma: the potential of combination strategies

That is a really important question. One of the challenges here is that even novel therapies, immune effector therapies like CAR-T therapy, extramedullary disease continues to be a marker of poor prognosis. When we looked at a large cohort of patients treated with ide-cel, over 350 patients, about one-fourth of them had true extramedullary disease. The median PFS there was five months. Recent data from cilta-cel demonstrated that PFS to be a little bit better at around seven to eight months, but still pretty dismal outcomes compared to patients when they don’t have extramedullary disease. There has been encouraging data that teclistamab and talquetamab combination seems to demonstrate very high overall response rates even in patients with extramedullary disease, and these responses seem to be durable. So maybe combination strategies with immune effector therapies is the way going forward in these tumors. But more therapies are needed, more targeted therapies and rational combinations are needed. From our data, potentially exploring a MYC inhibitor in combination with some of the strategies could be important. If we can somehow uncouple the MYC and MAX interaction with small molecule inhibitors, that could be an important therapeutic avenue to explore as well. We also noted some increased EP300 alterations, and there are small molecule inhibitors and clinical trials that are out there which could be explored specifically in extramedullary disease as well.

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