Multiple myeloma embodies the paradigm of the deepest the response the longer the survival. However, there are conflicting results between the achievement of complete remission and MRD negativity, because some patients with persistent M-protein have nonetheless undetectable MRD. We reviewed the frequency of this discordancy and the outcome of these patients. We spotlighted possible explanations and consequences of conflicting response criteria, and suggest that MRD should be assessed in patients achieving very good partial response or better in clinical trials.

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