CGC Plasma Cell Neoplasm Working Group recommendations for testing and reporting cytogenetic results for MM risk stratification

Fluorescence in situ hybridization (FISH) remains the gold-standard clinical assay in the genetic assessment of MM. However, clinical practices differ worldwide, including variations in FISH panel design, PC enrichment methodologies, use of conventional chromosome banding analysis, and reporting practices. The lack of standardization in cytogenetic testing in MM may result in confusion and raises the probability of incorrect integration of cytogenetic results in MM risk stratification. 

Lu et al. recently published the Cancer Genomics Consortium Plasma Cell Neoplasm Working Group guidelines for the testing and reporting of cytogenetic results for MM risk stratification in Blood Cancer Journal.¹ 

The CGC Plasma Cell Neoplasm Working Group comprised of 12 clinical cytogenetic laboratory directors from the CGC and 3 clinical MM oncologists who convened monthly for 1 hour for 1.5 years. Consensus recommendations were based on a literature review, a survey of 102 oncologists, and current risk-stratification guidelines.  

Key learnings

A minimum FISH assessment that includes TP53 deletion, 1q gain or amplification, 1p deletion, and primary IGH-r, including t(4;14)(p16;q32), t(14;16)(q32;q23), t(14;20)(q32;q12), t(11;14)(q13;q32), and t(6;14)(p21.1;q32), is recommended for all NDMM. If an IGH-r is identified, assessment of t(4;14), t(14;16), t(14;20), and t(11;14) is advised.

For RRMM, a minimal FISH assessment that includes TP53 deletion, 1p deletion, 1q gain or amplification, and at least one probe targeting the primary abnormality is recommended.

FISH reporting should highlight critical results, including a table, and use plain and standardized language that interprets the results with accurate classification into standard-risk and high-risk, based on the 2025 IMS/IMWG Risk Stratification Guidelines.

All samples should undergo PC enrichment to minimize the potential for false-negative test results. Validation of a workflow that prioritizes PC enrichment for FISH is recommended. Chromosome banding analysis results should be correlated with FISH results.

Improvements in FISH panel design, testing, and reporting practices are essential to improve clarity, reduce variability, and enhance patient care in MM.