Multiple myeloma gammopathies

Combination of flow cytometry and functional imaging for monitoring of residual disease in myeloma

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The iliac crest is the sampling site for minimal residual disease (MRD) monitoring in multiple myeloma (MM). However, the disease distribution is often heterogeneous, and imaging can be used to complement MRD detection at a single site. We have investigated patients in complete remission (CR) during first-line or salvage therapy for whom MRD flow cytometry and the two imaging modalities positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) were performed at the onset of CR. Residual focal lesions (FLs), detectable in 24% of first-line patients, were associated with short progression-free survival (PFS), with DW-MRI detecting disease in more patients. In some patients, FLs were only PET positive, indicating that the two approaches are complementary. Combining MRD and imaging improved prediction of outcome, with double-negative and double-positive features defining groups with excellent and dismal PFS, respectively. FLs were a rare event (12%) in first-line MRD-negative CR patients. In contrast, patients achieving an MRD-negative CR during salvage therapy frequently had FLs (50%). Multi-region sequencing and imaging in an MRD-negative patient showed persistence of spatially separated clones. In conclusion, we show that DW-MRI is a promising tool for monitoring residual disease that complements PET and should be combined with MRD.

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We thank the patients and staff of the Myeloma Institute, UAMS. We also thank the Department of Radiology, UAMS. This work was supported by P01 CA 55819 from the National Cancer Institute. LR was supported by the Deutsche Forschungsgemeinschaft (DFG). NW was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number P20GM125503.

Author contributions

Conception and design: NW, LR, GJM. Provision of study material or patients: DA, GJM, BB, FvR, MZ, ST, CS, FED, JE, AFW. Reporting imaging: MK, JM, RS, RVH. Data analysis: NW, LR, GG, DA, CA, MB, CPW, BAW. Wrote the paper: LR, NW, GJM. Reviewed and approved the paper: All authors.

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Correspondence to N. Weinhold.

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Conflict of interest

BB is a co-inventor on patents and patent applications related to use of GEP in cancer medicine that have been licensed to Quest diagnostics. The other authors declare that they have no conflict of interest.

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