COMy 2025 | The potential of sustained MRD negativity to guide maintenance discontinuation post-SCT in myeloma

I think this is a very important topic. So we are using MRD, we know that MRD negativity is an important prognostic factor and recently FDA has approved MRD as an endpoint in order to give approval to new drugs. However, we don’t know if we can use it in order to take treatment decisions. So one important treatment decision that we want to follow is if someone who is in sustained MRD negativity can stop treatment. I think that the best population that we can deal with that is a patient who is in maintenance therapy after autologous transplantation. 

So what we did in this study is that patients who had achieved MRD negativity, sustained MRD negativity in the bone marrow for three years, plus PET-CT negative for three years, then we stopped lenalidomide maintenance. All these patients were patients who were eligible for transplant. They had received a triplet, the majority of them, mainly VRd, plus autologous transplant, plus lenalidomide maintenance. So 25% of the whole population of these patients in our center had this inclusion criteria – three years of sustained MRD negativity plus imaging MRD negativity. And then, according to the study, we stopped maintenance and we followed the patient. 

Also this study has another important feature that, at the time of MRD positivity after the MRD negativity, then the patient could restart lenalidomide maintenance at the dose of lenalidomide when the patient stopped maintenance in order to check if the patient can reverse to MRD negativity again. 

So what we’ve seen that almost one fourth, I think it was 23% of the patients within the three-year median follow-up become from MRD negative to MRD positive. But only four of them, the majority with high-risk disease, had biochemical relapse, which is 7% of the total of 52 patients who participated in the study. So it was four out of the 52 patients, so 7% biochemical relapse. Nobody had a biochemical relapse before going from the MRD negativity to MRD positivity. 

Just to let you know that for the follow-up of the study, every six months we had a bone marrow in order to evaluate the MRD negativity in the marrow, and every year the patients had a PET scan. So I think that this is important. 

The second important issue is that from this 23% of the patients who become from MRD-negative to MRD-positive, the re-administration of lenalidomide managed to reverse this MRD-positivity to MRD-negativity only in one patient. So it seems that the restart of lenalidomide did not help a lot. Of course, we need a bigger number of patients in order to know that. But in general, I would say that our study suggests that, especially patients with standard risk disease, after three years of sustained MRD negativity in the bone marrow and sustained imaging MRD negativity could stop lenalidomide maintenance. I think this is the message of this study.

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