Molecular detection of minimal residual disease in multiple myeloma

• Published in: British journal of haematology Vol. 181; no. 1; pp. 11 - 26
• Main Authors: Bai, Yinlei, Orfao, Alberto, Chim, Chor Sang
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2018
• Subjects: allele‐specific oligonucleotide PCR; digital PCR; Flow cytometry; Hematology; High-Throughput Nucleotide Sequencing - methods; Humans; Minimal residual disease; Multiple myeloma; Multiple Myeloma - blood; Multiple Myeloma - genetics; Neoplasm, Residual - blood; Neoplasm, Residual - genetics; next‐generation sequencing; Oligonucleotides; Peripheral blood; Polymerase chain reaction; Polymerase Chain Reaction - methods; Remission; Sensitivity; Tumors; multiple myeloma; minimal residual disease; allele-specific oligonucleotide PCR; digital PCR; next-generation sequencing
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.15075

Summary Despite the significantly higher complete remission rates and improved survival achieved in the last decade, multiple myeloma (MM) patients continue to relapse due to persistence of minimal residual disease (MRD). Generally, MRD refers to persistence of low levels of disease in the order of one tumour cell in ≥105 normal cells. Currently, molecular and immunophenotypic techniques are employed for MRD detection. This review focuses on MRD detection by molecular techniques, including allele‐specific oligonucleotide polymerase chain reaction (ASO‐PCR), next‐generation sequencing (NGS) and digital PCR (dPCR), in addition to a brief description of, and comparison with, multiparameter flow cytometry. The basic principles, technical advantages and limitations, and the clinical impact of all three molecular techniques are reviewed and compared. They all have a sensitivity of at least 10−5, among which ASO real‐time quantitative PCR is the most well‐standardized, and NGS carries the highest sensitivity and applicability, while dPCR is still under investigation. Furthermore, molecular MRD negativity is a favourable prognostic factor for survival of patients with MM. However, several challenges inherent to molecular detection of MRD still remain to be overcome, particularly false negativity and failure to detect extramedullary disease. Finally, detection of MRD from peripheral blood remains challenging.