Prognostic significance of sequencing-based MRD detection in multiple myeloma

Abstract

Stem cell transplantation in conjunction with therapeutic agents such as proteasome inhibitors and immunomodulatory drugs 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. We utilized a deep sequencing method, which employs consensus primers and next-generation sequencing (NGS), to amplify and sequence all rearranged immunoglobulin gene segments present in a myeloma clone. This technique has been shown to have 1-2 log greater sensitivity than both allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) (sensitivity 10(-5)) and multiparameter flow cytometry (MFC) (sensitivity at least 10(-4)). To investigate the value of sensitive detection of MRD in autograft by NGS, we compared progression-free survival (PFS) in 11 MRDNGS(-) cases (Group 1) with that in 12 MRDNGS(+) cases in which MRD was not detected by ASO-PCR (MRDASO(-)) (Group 2). Neither group received any post-ASCT therapy. Group 1 showed a better PFS than Group 2 (P=0.027). MRD-negativity in autografts, as revealed by NGS, is more closely associated with durable remission of MM than that revealed by ASO-PCR.