Prognostic value of sequencing-based minimal residual disease detection in patients with multiple myeloma who underwent autologous stem-cell transplantation.
Prognostic value of sequencing-based minimal residual disease detection in patients with multiple myeloma who underwent autologous stem-cell transplantation.
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DOI：
10.1093/annonc/mdx340
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发表时间：
2017-10-01
期刊：
影响因子：
--
通讯作者：
Nakao S
中科院分区：
文献类型：
--
作者：
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
多发性骨髓瘤（MM）患者大多数被认为是不可治愈的，由于微小残留病（MRD）而导致的复发是这些患者死亡的主要原因。因此，需要新的技术来评估更深层次的反应。我们回顾性分析了125例接受大剂量美法仑联合自体干细胞移植（ASCT）的MM患者，使用基于下一代测序（NGS）的方法和等位基因特异性寡核苷酸聚合酶链反应（ASO-PCR）检测自体移植物/骨髓（BM）细胞中的MRD。基于NGS的方法适用于90%，与ASO-PCR相比，该方法的灵敏度至少高出一到两个对数。ASCT后BM病例（n = 26）中NGS MRD阴性[MRDNGS（−）]（定义为<10−6）显示，与ASCT后BM病例（n = 25）中MRDNGS（+）相比，无进展生存期（PFS）（4年时96%，P < 0.001）和总生存期（OS）（4年时100%，P =0.04）显著更好。当将分析限制在39例完全缓解病例时，MRDNGS（-）患者（n = 24）的PFS显著优于MRDNGS（+）患者（n = 15）（P =0.02）。此外，ASCT后BM病例（n = 12）中的MRDNGS（-）显示PFS显著优于MRDNGS（+）病例（n = 7），其中ASO-PCR未检测到MRD（P = 0. 001）。自体移植物经基于NGS的MRD评估为阴性的患者（<10−7）（n = 19）在ASCT后4年时的PFS为92%，OS为100%。相反，接受ASCT后使用新型药物治疗的基于NGS的MRD阳性患者（n = 49）的PFS（P = 0.001）显著优于未接受治疗的患者（n = 33），OS（P= 0.214）也更好。当评估ASCT后自体移植物产物或BM细胞时，通过基于NGS的平台而不是ASO-PCR检测到的低水平MRD具有显著的预后价值。
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. 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). 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). 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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