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COMy 2026 | Recent advances and unmet needs in smoldering multiple myeloma
Kwee Yong, MD, PhD, FRCP, FRCPath, University College London, London, UK, shares recent updates in smoldering multiple myeloma (SMM), explaining that key gaps remain in understanding the genomic drivers of progression and immune function within the bone marrow microenvironment. Prof. Yong also outlines several ongoing trials, including the Phase III ITHACA (NCT04270409) and Phase II CAR-PRISM (NCT05767359) studies, noting that navigating treatment options can be challenging for patients. This interview took place at the 12th World Congress on Controversies in Multiple Myeloma (COMy) in Paris, France.
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Transcript
Smoldering myeloma continues to be a very busy area, both for clinical research, basic laboratory research, and also clinical trials. I think that with regard to basic science, we’re only just scratching the surface of the immune dysregulation and the genomic drivers of progression to myeloma. Much of the discussion in sessions is focused on Francesco Maura’s recent paper dividing precursor condition patients into those with a transformed genome and a non-transformed genome...
Smoldering myeloma continues to be a very busy area, both for clinical research, basic laboratory research, and also clinical trials. I think that with regard to basic science, we’re only just scratching the surface of the immune dysregulation and the genomic drivers of progression to myeloma. Much of the discussion in sessions is focused on Francesco Maura’s recent paper dividing precursor condition patients into those with a transformed genome and a non-transformed genome. The problem is that for individuals with a transformed genome, their risk of progression could be high or it could be low, and that depends on so many other features. So just having a transformed genome doesn’t necessarily mark someone out as somebody who needs treatment. So we still have many missing pieces of the puzzle, and almost certainly some of those missing pieces of the puzzle will come from immunology and studying the immune function, and particularly in the microenvironment. And I think that some of the work that was described by Dhodapkar, looking at the spatial relationships within the bone marrow environment, will be key. So there’s much to learn in the basic biology. But for clinical trials, we have the ITHACA study, which we’ll hopefully report next year, combination of CD38 antibody, isatuximab with lenalidomide. And recently published, I think just two or three weeks ago in the New England Journal was the cilta-cel study from the Dana-Farber group using CAR T-cells in high-risk smoldering myeloma with some very nice immunological and clinical correlates. So a very busy area and I think quite difficult for patients to negotiate in terms of whether they need treatment, whether they will benefit from treatment, and if so, what might be the best.
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