Prognostic value of minimal residual disease response assessment in multiple myeloma

Abstract

Stem cell transplantation in conjunction with therapeutic drugs such as bortezomib, thalidomide, and lenalidomide can dramatically improve response rates and the prognoses of patients with multiple myeloma (MM). However, most patients with MM are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients. The International MyelomaWorking Group approved the definition of immunophenotypic complete response (iCR) using multiparametric flow cytometry (MFC) (sensitivity at least 10-4) and molecular complete response (mCR) as complete response plus a negative allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) (sensitivity 10-5) in assessing MRD. MFC is inexpensive and MRD results can be rapidly obtained; however, the method, which uses at least four colors, has not been standardized worldwide. In addition, there may be an issue of false-negative results owing to the lack of immunophenotype stability. Although mCR in MM can be assessed by ASO-PCR, this technique requires the preparation of clonotype-specific primers for each individual, a process which is laborious and time-consuming. We utilized a sequencing method (LymphoSIGHTTM platform from Sequenta), which employs consensus primers and next-generation sequencing (NGS), to amplify and sequence all rearranged immunoglobulin gene segments present in a myeloma clone. Although this technique has been shown to have 1-2 logs greater sensitivity compared to both ASO-PCR and MFC, the sensitivity of NGS is dependent on the amount of DNA present in samples for the MRD assessment. In this symposium, I would like to discuss the advantages and disadvantages of these MRD assessment methods and how to use them in clinical settings, including HLA haploidentical hematopoietic stem cell transplantation against MM.