Prognostic value of sequencing-based minimal residual disease detection in patients with multiple myeloma who underwent autologous stem-cell transplantation

Abstract

Background

Most patients with multiple myeloma (MM) are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients. Therefore, new technologies to assess deeper response are required.

Patients and methods

We retrospectively analyzed 125 patients with MM who underwent high-dose melphalan plus autologous stem-cell transplantation (ASCT) to detect MRD in autograft/bone marrow (BM) cells using a next-generation sequencing (NGS)-based method and allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR).

Results

NGS-based method was applicable to 90% and this method had at least one to two logs greater sensitivity compared to ASO-PCR. MRD negative by NGS [MRD ^NGS(−)] (defined as <10 ⁻⁶) in post-ASCT BM cases ( n =  26) showed a significantly better progression-free survival (PFS) (96% at 4 years, P < 0.001) and overall survival (OS) (100% at 4 years, P =0.04) than MRD ^NGS(+) in post-ASCT BM cases ( n =  25). When restricting the analysis to the 39 complete response cases, patients who were MRD ^NGS(−) ( n =  24) showed a significantly better PFS than those that were MRD ^NGS(+) ( n =  15) ( P =0.02). Moreover, MRD ^NGS(−) in post-ASCT BM cases ( n =  12) showed significantly a better PFS than MRD ^NGS(+) cases ( n =  7) where MRD was not detected by ASO-PCR ( P =  0.001). Patients whose autografts were negative by NGS-based MRD assessment (<10 ⁻⁷) ( n =  19) had 92% PFS and 100% OS at 4 years post-ASCT. Conversely, the NGS-based MRD positive patients who received post-ASCT treatment using novel agents ( n =  49) had a significantly better PFS ( P = 0.001) and tended to have a better OS ( P= 0.214) than those that were untreated ( n =  33).

Conclusions

Low level MRD detected by NGS-based platform but not ASO-PCR has significant prognostic value when assessing either the autograft product or BM cells post-ASCT.