TY - CHAP
T1 - Minimal residual disease in multiple myeloma
T2 - impact on response assessment, prognosis and tumor heterogeneity
AU - Berger, Natalie
AU - Kim-Schulze, Seunghee
AU - Parekh, Samir
N1 - Publisher Copyright:
© Springer Nature Switzerland AG 2018.
PY - 2018
Y1 - 2018
N2 - Multiple Myeloma (MM) therapy has evolved rapidly over the past decade. With current multidrug combinations and autologous transplant, rates of overall response exceed 90% and complete response (CR) more than 50% in some studies. Unfortunately, despite higher rates of CR, relapse rates remain high suggesting that persistent disease may not be measured by current techniques. Traditionally, response rates were defined by urine and serum protein electrophoresis, immunofixation and histopathological absence of clonal plasma cells in the bone marrow. Currently, there are several validated sensitive assays to evaluate for MRD (minimal residual disease); multiparameter flow cytometry (MFC) including nextgeneration flow cytometry (NGF), next-generation sequencing (NGS), and allele specific oligonucleotide quantitative polymerase chain reaction (ASO-qPCR). These methods have provided a means to quantitatively assess residual disease and accurately prognosticate PFS and OS in myeloma. In this chapter, we will discuss the current techniques for MRD detection as well as describe techniques that are emerging for improved characterization of drug resistant residual populations that could be adapted for MRD monitoring in the future. While improved therapies are able to eradicate the dominant clone, resistant sub-clones persist and remain undetectable even by MRD techniques. Characterization of these clones will help design therapies against drug-resistant clones and move us closer to a cure in MM.
AB - Multiple Myeloma (MM) therapy has evolved rapidly over the past decade. With current multidrug combinations and autologous transplant, rates of overall response exceed 90% and complete response (CR) more than 50% in some studies. Unfortunately, despite higher rates of CR, relapse rates remain high suggesting that persistent disease may not be measured by current techniques. Traditionally, response rates were defined by urine and serum protein electrophoresis, immunofixation and histopathological absence of clonal plasma cells in the bone marrow. Currently, there are several validated sensitive assays to evaluate for MRD (minimal residual disease); multiparameter flow cytometry (MFC) including nextgeneration flow cytometry (NGF), next-generation sequencing (NGS), and allele specific oligonucleotide quantitative polymerase chain reaction (ASO-qPCR). These methods have provided a means to quantitatively assess residual disease and accurately prognosticate PFS and OS in myeloma. In this chapter, we will discuss the current techniques for MRD detection as well as describe techniques that are emerging for improved characterization of drug resistant residual populations that could be adapted for MRD monitoring in the future. While improved therapies are able to eradicate the dominant clone, resistant sub-clones persist and remain undetectable even by MRD techniques. Characterization of these clones will help design therapies against drug-resistant clones and move us closer to a cure in MM.
KW - ASO-qPCR
KW - Bone marrow
KW - CD138
KW - ECM
KW - MRD
KW - Mass cytometry
KW - Microenvironment
KW - Multiparametric flow cytometry
KW - Multiple myeloma
KW - Next generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=85056416273&partnerID=8YFLogxK
U2 - 10.1007/978-3-319-97746-1_9
DO - 10.1007/978-3-319-97746-1_9
M3 - Chapter
C2 - 30411265
AN - SCOPUS:85056416273
T3 - Advances in Experimental Medicine and Biology
SP - 141
EP - 159
BT - Advances in Experimental Medicine and Biology
PB - Springer New York LLC
ER -