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

Hiroyuki Takamatsu, N. Takezako, J. Zheng, M. Moorhead, V. E.H. Carlton, K. A. Kong, R. Murata, S. Ito, Toshihiro Miyamoto, K. Yokoyama, K. Matsue, T. Sato, T. Kurokawa, H. Yagi, Y. Terasaki, K. Ohata, M. Matsumoto, T. Yoshida, M. Faham, S. Nakao

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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.

Original languageEnglish
Pages (from-to)2503-2510
Number of pages8
JournalAnnals of Oncology
Volume28
Issue number10
DOIs
Publication statusPublished - Jan 1 2017

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Residual Neoplasm
Stem Cell Transplantation
Multiple Myeloma
Disease-Free Survival
Autografts
Alleles
Polymerase Chain Reaction
Bone Marrow
Bone Marrow Cells
Survival
Melphalan
Cause of Death

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

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Prognostic value of sequencing-based minimal residual disease detection in patients with multiple myeloma who underwent autologous stem-cell transplantation. / Takamatsu, Hiroyuki; Takezako, N.; Zheng, J.; Moorhead, M.; Carlton, V. E.H.; Kong, K. A.; Murata, R.; Ito, S.; Miyamoto, Toshihiro; Yokoyama, K.; Matsue, K.; Sato, T.; Kurokawa, T.; Yagi, H.; Terasaki, Y.; Ohata, K.; Matsumoto, M.; Yoshida, T.; Faham, M.; Nakao, S.

In: Annals of Oncology, Vol. 28, No. 10, 01.01.2017, p. 2503-2510.

Research output: Contribution to journalArticle

Takamatsu, H, Takezako, N, Zheng, J, Moorhead, M, Carlton, VEH, Kong, KA, Murata, R, Ito, S, Miyamoto, T, Yokoyama, K, Matsue, K, Sato, T, Kurokawa, T, Yagi, H, Terasaki, Y, Ohata, K, Matsumoto, M, Yoshida, T, Faham, M & Nakao, S 2017, 'Prognostic value of sequencing-based minimal residual disease detection in patients with multiple myeloma who underwent autologous stem-cell transplantation', Annals of Oncology, vol. 28, no. 10, pp. 2503-2510. https://doi.org/10.1093/annonc/mdx340
Takamatsu, Hiroyuki ; Takezako, N. ; Zheng, J. ; Moorhead, M. ; Carlton, V. E.H. ; Kong, K. A. ; Murata, R. ; Ito, S. ; Miyamoto, Toshihiro ; Yokoyama, K. ; Matsue, K. ; Sato, T. ; Kurokawa, T. ; Yagi, H. ; Terasaki, Y. ; Ohata, K. ; Matsumoto, M. ; Yoshida, T. ; Faham, M. ; Nakao, S. / Prognostic value of sequencing-based minimal residual disease detection in patients with multiple myeloma who underwent autologous stem-cell transplantation. In: Annals of Oncology. 2017 ; Vol. 28, No. 10. pp. 2503-2510.
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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.",
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T1 - Prognostic value of sequencing-based minimal residual disease detection in patients with multiple myeloma who underwent autologous stem-cell transplantation

AU - Takamatsu, Hiroyuki

AU - Takezako, N.

AU - Zheng, J.

AU - Moorhead, M.

AU - Carlton, V. E.H.

AU - Kong, K. A.

AU - Murata, R.

AU - Ito, S.

AU - Miyamoto, Toshihiro

AU - Yokoyama, K.

AU - Matsue, K.

AU - Sato, T.

AU - Kurokawa, T.

AU - Yagi, H.

AU - Terasaki, Y.

AU - Ohata, K.

AU - Matsumoto, M.

AU - Yoshida, T.

AU - Faham, M.

AU - Nakao, S.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

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