Table 5 High-risk features for newly diagnosed multiple myeloma.

From: High-risk disease in newly diagnosed multiple myeloma: beyond the R-ISS and IMWG definitions

 

High risk

Potentially high risk (more data needed)

Currently Utilized Staging systems:

R-ISS stage 3

IMWG high-risk

mSMART high risk

 

High-risk cytogenetic changesa

• t(14;16)

• t(4;14)

• IgL-MYC translocation

• +1q amplification (≥4 copies): 20% CCF

• 1p-

• del(17p): 55–60% CCF

• t(14;20)

• t(8;14) and other MYC translocations

• +1q gain (3 copies)

• del 13q/-13

GEP-results

EMC92/SYK92 (MMprofiler): high-risk

UAMS GEP70 (MyPRS): high risk

 

Mutations obtained by whole-genome/exome sequencing

• TP53 deletion

• LOH and APOEBEC signature

• CKS1B amplification

• "High Risk Genomic Clusters"b

• TRAF3

• TGDS

• PRDM1

• DNAH11

• FAT1

• NRAS

• SP140

• IGLL5

• Driver gene mutational burden

Clinical Features and disease burden:

• High Plasma Cell Labeling Index

• Extramedullary Myeloma

• Focal Lesions (FL): 3 large FLs with a product of the perpendicular diameters >5 cm2

• Clinical frailty by objective geriatric assessment

Socioeconomic status

  1. GEP gene-expression profiling, IMWG international myeloma working group, LOS loss of heterozygosity, MM multiple myeloma, R-ISS revised international staging system.
  2. aTranslocations and copy number abnormalities (independent of other features) with cancer clone fraction cutoffs where enough data supports a conclusion.
  3. bSee Table 4.
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