IMS 2025 | Updates on current research exploring treatment strategies for high-risk smoldering myeloma
Karthik Ramasamy, MBBS, MRCP, FRCPath, PhD, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, shares updates on current research exploring potential treatment strategies for high-risk smoldering myeloma. The AQUILA study (NCT03301220) showed the benefit of daratumumab monotherapy in these patients, prompting the exploration of several agents outlined by Dr Ramasamy. This interview took place at the 22nd International Myeloma Society (IMS) Annual Meeting in Toronto, Canada.
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Transcript
High-risk smoldering myeloma is an active space for interventions to be tested because we now have daratumumab close to approval in the United States based on the AQUILA study. What the AQUILA study explored is a comparison of daratumumab monotherapy versus no treatment for a fixed duration of three years. And the study demonstrated that daratumumab therapy can significantly reduce the proportion of patients converting to active myeloma at a time point of about five years...
High-risk smoldering myeloma is an active space for interventions to be tested because we now have daratumumab close to approval in the United States based on the AQUILA study. What the AQUILA study explored is a comparison of daratumumab monotherapy versus no treatment for a fixed duration of three years. And the study demonstrated that daratumumab therapy can significantly reduce the proportion of patients converting to active myeloma at a time point of about five years. Therefore, there’s a lot of activity exploring new treatments in the high-risk smoldering myeloma space. There are both treatments which combine CD38 and immunomodulatory drugs that are currently ongoing. There is a daratumumab lenalidomide dexamethasone study against lenalidomide in a randomized fashion. This isatuximab lenalidomide dexamethasone versus lenalidomide dexamethasone in the ATTACHER study; we’re waiting for results from these randomized studies. In the UK, we’ve taken an approach of using a combination of isatuximab with pomalidomide and dexamethasone for a two-year fixed duration, but there’s one element which is exciting and there’s more data at the IMS meeting: can we use BCMA-targeted agents in high-risk smoldering myeloma? Would that give us better responses and longer responses? These are the questions being asked and data being presented around siltuximab use in the newly diagnosed setting, as well as teclistamab used in the newly diagnosed setting. And there’s also data from linvo-celtamab, which is another BCMA-bispecific antibody in smoldering myeloma that’s being presented. So all of these explore whether BCMA targeting is more effective than the CD38-based platforms that we have used to date. And we have to look at this data more carefully and start to make better plans in high-risk smoldering myeloma in the future.
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