IMS 2026 | Identifying patients who need curative treatment versus disease control in myeloma

So I think there have been data, you know, presented over the years from the MAIA study or from the TechLeal study. Let me start with the MAIA trial of Dara-Rd, Dara, lenalidomide, dexamethasone. Five-year overall survival in that patient population who are older, frailer, non-transplanted is well over five years. And again, there’s emerging data that for those patients, Dara-Rd, believe it or not, is a functional cure for those patients. They live for as long as they’re going to live and they die of something else. That sounds like a very morbid way of describing things, but the myeloma is not the cause of death. They’ve lived as long as they’re supposed to live. I will call that a functional cure for patients. They didn’t need to be cured, cured. Those patients did not need full-intensity treatment, including transplant or CAR T or bispecifics to get them there. I think I wouldn’t say that we’re avoiding the question. I would say that we’re working on it. I think the key point here is that we can borrow from our understanding of MGUS, of smoldering myeloma. There’s an emerging consensus here that some patients with smoldering myeloma have genomic myeloma. Those precancerous patients already have cancer. We just don’t know it yet. It hasn’t caused any SLiM-CRAB criteria versus some of those patients are just genomic MGUS. Those patients do not need to be cured. They’re going to live their whole life without any problems. Increasingly, I think after myeloma treatment, it turns out that some patients revert to what is called an MGUS-like phenotype, where now using more scientific language, they are still MRD-positive, but they do excellently. We don’t yet know who those patients are. You know, I don’t yet have a way. If someone’s MRD-positive, all I have is a number. I have a number of abnormal cells. It doesn’t tell me if they’re cancer cells or precancer-like, MGUS-like cells. I just know that they’re there. There are companies like PlasmaSeq, Genopredicta, and others working on being able to sequence those cells, understand mutations in those cells, understand how malignant those cells are. We already have some of these tools. Actually, Dr Martin Kaiser has done a lot of work around some of these mRNA-based profiling of these cells, you know, to identify, actually, he’s able to identify who is going to be functional high-risk or not, who is going to have an early relapse versus not. For everybody who does not have genomically high-risk residual cells, they just have more MGUS-like cells, those patients do not need to be cured. They will smolder in that MGUS-like category for as long as they live without any issues. To come full circle to your question, I don’t yet know who those patients are in their entirety. I will tell you that the chapter is still being written on t(11;14). There were very interesting data presented last December by Luciano Costa and colleagues showing that t(11;14) myeloma is less likely to achieve MRD negativity despite a quad regimen from Dara-KRd and transplant, but they paradoxically do better. It’s better to be MRD-positive with t(11;14), meaning non-cured, t(11;14), than it is to have non-t(11;14) and be MRD-negative, which is just mind-boggling to me. The MIDAS trial of Isa-KRd reached similar conclusions with t(11;14). So I think probably for those patients, I would be comfortable not curing them. As long as the MRD burden is stable, the M-spike is stable, as long as the M-spike is not bugging them, it’s not bugging me. That is not a very scientific way to approach things. So we have work to do, but I think we’re working on it. Ultimately, the conclusion will come down to better diagnostics to understand of the patient with a residual disease. That just tells you a number. It doesn’t tell you qualitatively what the type of cells are. It only gives you a quantitative number. But we can figure out qualitatively, are these cells in need of a cure or not? Is the patient in need of a cure or not? We’ll be able to identify those patients much better.

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