Deep MRD profiling defines outcome and unveils different modes of treatment resistance in standard- and high-risk myeloma.

Blood
Ibai GoicoecheaBruno Paiva

Abstract

Patients with multiple myeloma (MM) carrying standard- or high-risk cytogenetic abnormalities (CAs) achieve similar complete response (CR) rates, but the later have inferior progression-free survival (PFS). This questions the legitimacy of CR as a treatment endpoint and represents a biological conundrum regarding the nature of tumor reservoirs that persist after therapy in high-risk MM. We used next-generation flow (NGF) cytometry to evaluate measurable residual disease (MRD) in MM patients with standard- vs high-risk CAs (n = 300 and 90, respectively) enrolled in the PETHEMA/GEM2012MENOS65 trial, and to identify mechanisms that determine MRD resistance in both patient subgroups (n = 40). The 36-month PFS rates were higher than 90% in patients with standard- or high-risk CAs achieving undetectable MRD. Persistent MRD resulted in a median PFS of ∼3 and 2 years in patients with standard- and high-risk CAs, respectively. Further use of NGF to isolate MRD, followed by whole-exome sequencing of paired diagnostic and MRD tumor cells, revealed greater clonal selection in patients with standard-risk CAs, higher genomic instability with acquisition of new mutations in high-risk MM, and no unifying genetic event driving MRD resistance. C...Continue Reading

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Citations

Dec 2, 2020·Cancers·Titouan CazaubielAurore Perrot
Jan 8, 2021·Blood·Jill Corre
Mar 10, 2021·Skeletal Radiology·Megan J FitzpatrickAliyah R Sohani
Apr 4, 2021·Cancers·Anaïs SchavgoulidzeJill Corre
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May 21, 2021·Leukemia·Francesco MauraOla Landgren
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Jul 30, 2021·Blood·Mohamad MohtyJean-Luc Harousseau

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