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Ann Oncol. 2017 Oct 1;28(10):2503-2510. doi: 10.1093/annonc/mdx340.

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

Author information

1
Hematology/Respiratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa.
2
Department of Hematology, National Hospital Organization Disaster Medical Center of Japan, Tachikawa, Japan.
3
Adaptive Biotechnologies Corp., South San Francisco, USA.
4
Division of Internal Medicine, Keiju Kanazawa Hospital, Kanazawa.
5
Department of Medical Oncology, Iwate Medical University School of Medicine, Morioka.
6
Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
7
Department of Hematology/Oncology, Tokai University Hachioji Hospital, Hachioji.
8
Division of Hematology/Oncology, Department of Medicine, Kameda Medical Center, Kamogawa.
9
Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo.
10
Department of Hematology, Toyama Red Cross Hospital, Toyama.
11
Department of Hematology, Kinki University School of Medicine Nara Hospital, Ikoma, Nara.
12
Division of Internal Medicine, Toyama City Hospital, Toyama.
13
Department of Hematology, National Hospital Organization Shibukawa Medical Center, Shibukawa.
14
Department of Hematology, Shizuoka City Shimizu Hospital, Shizuoka, Japan.

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 [MRDNGS(-)] (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 MRDNGS(+) in post-ASCT BM cases (n = 25). When restricting the analysis to the 39 complete response cases, patients who were MRDNGS(-) (n = 24) showed a significantly better PFS than those that were MRDNGS(+) (n = 15) (P =0.02). Moreover, MRDNGS(-) in post-ASCT BM cases (n = 12) showed significantly a better PFS than MRDNGS(+) 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.

KEYWORDS:

autologous stem-cell transplantation; minimal residual disease; myeloma; next-generation sequencing

PMID:
28945825
PMCID:
PMC5834061
DOI:
10.1093/annonc/mdx340
[Indexed for MEDLINE]
Free PMC Article

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