Blood: The detection of negative micro-residual lesions should be used as the end point for the treatment of high-risk multiple myeloma.

Patients with high CA risk with multiple myeloma (MM) have a similar rate of total remission (CR) compared to cases with a standard cytogenetic abnormality (CA) risk.
this questions the rationality of CR as the end point of treatment for high-risk MM and represents a biological challenge for standard and high-risk CA patients to remain tumor cells after treatment.
Goicoechea, etc. use second-generation streaming (NGF) to evaluate the criteria for recruitment of PETHEMA/GEM2012MENOS65 (n-300) vs high CA risk MM patients with detectable residual lesions (MRD) to clarify the mechanism for determining MRD resistance in two patient subgroups.
36-month progression-free survival and total survival rates were higher than 90%, and there was no significant difference between cases with standard risk or high CA risk (P-0.202).
sustained MRD resulted in a median progression-free survival of only about 3 years and 2 years for patients with high CA risk (P.lt;0.001), respectively.
further isolated MRD with NGF, and then the paired MRD tumor cells were sequenced genome-wide, and found that MM patients with standard CA risk had more cloning options, high-risk MM patients had more secondary mutations, higher genomic instability, and no uniform absence or acquired genetic variation that drove MRD resistance was found.
, incontrast, RNA sequencing of MRD tumor cells revealed mrD cloning options with a single transcription program and ROS-mediated MRD resistance in high-risk Mm.
this study supports the detection of MRD as a therapeutic endpoint for MM patients at high CA risk, and proposes the prostheticization of MRD cloning to understand and overcome MRD resistance.
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