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IMS 2025 | How do outcomes differ when myeloma treatment begins at MRD positivity versus symptomatic relapse?
Fredrik Schjesvold, MD, PhD, Oslo University Hospital, Oslo, Norway, comments on the benefits of early treatment in multiple myeloma, citing evidence that starting treatment early is associated with improved overall and progression-free survival. He discusses the ongoing REMNANT study (NCT04513639), which will evaluate outcomes of treatment given at measurable residual disease (MRD) relapse versus progressive disease. This interview took place at the 22nd International Myeloma Society (IMS) Annual Meeting in Toronto, Canada.
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Transcript
Well, we don’t know. But we have many indications that starting treatment early is beneficial for patients in many situations. We know that patients with known monoclonal gammopathy before they get the diagnosis myeloma live longer after the diagnosis, so it’s good to start as early as possible. We know that treating smoldering myeloma from the AQUILA trial and the QuiRedex trial increases overall survival in myeloma...
Well, we don’t know. But we have many indications that starting treatment early is beneficial for patients in many situations. We know that patients with known monoclonal gammopathy before they get the diagnosis myeloma live longer after the diagnosis, so it’s good to start as early as possible. We know that treating smoldering myeloma from the AQUILA trial and the QuiRedex trial increases overall survival in myeloma. We know that at diagnosis if your tumor load is higher your overall survival is lower. We know from relapse studies that if your tumor load is higher your survival is lower. So all these things together tell us that treating earlier gives better results. There’s also a sort of translational aspect here. We know that mutations where refractoriness does not come from treatment. It comes from cell divisions. The higher your tumor load is at any given time, the more cell divisions and the more mutations you will have creating refractoriness. So that’s also an indication that keeping tumor load low, treating relapse early, treating at diagnosis early is beneficial for the patients. What we do know in a relapse setting is that it’s better, it gives better overall survival and progression-free survival to treat at biochemical progression than to treat at symptomatic relapse. We have data from this, both from the Mayo Clinic and from Greek data. What we have not seen is that established in a clinical randomized trial, and we have not established it for MRD positivity. So that’s why we have done or are doing the REMNANT trial where we treat patients or randomize patients who are MRD negative CR after first-line treatment and randomize them to get the same treatment at MRD relapse or at progressive disease. The study is fully enrolled with 200 MRD negative patients in CR and the group A will get Dara-Kd at MRD positivity or loss of CR and group B will get Dara-Kd at progressive disease and we will see whether this can show what is the benefit in terms of progression survival and overall survival. But for now we have to wait for the results and they will be exciting when they come.
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