COMy 2025 | Investigating molecular characteristics of patients with myeloma and EMD: findings & implications

Extramedullary disease, as you all know, is a challenge and I think we are beginning to see more of that challenge now in the context of bispecifics and CAR T-cells. So patients are living a lot longer but when they relapse, specifically with high-risk disease, we do see the resurgence of extramedullary disease. We have done sort of molecular typing of these patients with EMD, we’ve most recently published this, and what we’ve seen is there’s a predominance of NRAS KRAS mutations in this patient population there’s a slightly higher incidence of BRAF. We specifically looked at non-boney soft tissue extramedullary disease, so true true EMD, and what we found was a slight increase in certain mutations and these were ADAR1 mutations. ADAR1 is a new gene which is seen in myeloma. We don’t quite know the significance. We know that some of these patients can have a poorer prognosis, but we did see an ADAR1 mutation in the majority of patients with EMD. Now this has obvious implications because if we know that it’s NRAS, KRAS, BRAF as well as these ADAR1 mutations, can we think about these differently and can we start targeting these patients with different maybe MEK inhibitors, BRAF inhibitors, I don’t know the answer to that but at least we have some data to support that these mutations are enriched in patients with EMD.

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