自体干细胞移植后多发性骨髓瘤患者的微小残留病：预后意义和来那度胺维持治疗及分子风险的影响。
Minimal Residual Disease After Autologous Stem-Cell Transplant for Patients With Myeloma: Prognostic Significance and the Impact of Lenalidomide Maintenance and Molecular Risk.
机构信息
Haematological Malignancy Diagnostic Service, Leeds Cancer Centre, Leeds Teaching Hospitals Trust, Leeds, United Kingdom.
The Institute of Cancer Research, London, United Kingdom.
出版信息
J Clin Oncol. 2022 Sep 1;40(25):2889-2900. doi: 10.1200/JCO.21.02228. Epub 2022 Apr 4.
PURPOSE
Minimal residual disease (MRD) can predict outcomes in patients with multiple myeloma, but limited data are available on the prognostic impact of MRD when assessed at serial time points in the context of maintenance therapy after autologous stem-cell transplant (ASCT) and the interaction between MRD and molecular risk.
METHODS
Data from a large phase III trial (Myeloma XI) were examined to determine the relationship between MRD status, progression-free survival (PFS), and overall survival (OS) in post-ASCT patients randomly assigned to lenalidomide maintenance or no maintenance at 3 months after ASCT. MRD status was assessed by flow cytometry (median sensitivity 0.004%) before maintenance random assignment (ASCT + 3) and 6 months later (ASCT + 9).
RESULTS
At ASCT + 3, 475 of 750 (63.3%) patients were MRD-negative and 275 (36.7%) were MRD-positive. MRD-negative status was associated with improved PFS (hazard ratio [HR] = 0.47; 95% CI, 0.37 to 0.58 < .001) and OS (HR = 0.59; 95% CI, 0.40 to 0.85; = .0046). At ASCT + 9, 214 of 326 (65.6%) were MRD-negative and 112 (34.4%) were MRD-positive. MRD-negative status was associated with improved PFS (HR = 0.20; 95% CI, 0.13 to 0.31; < .0001) and OS (HR = 0.33; 95% CI, 0.15 to 0.75; = .0077). The findings were very similar when restricted to patients with complete response/near complete response. Sustained MRD negativity from ASCT + 3 to ASCT + 9 or the conversion to MRD negativity by ASCT + 9 was associated with the longest PFS/OS. Patients randomly assigned to lenalidomide maintenance were more likely to convert from being MRD-positive before maintenance random assignment to MRD-negative 6 months later (lenalidomide 30%, observation 17%). High-risk molecular features had an adverse effect on PFS and OS even for those patients achieving MRD-negative status. On multivariable analysis of MRD status, maintenance therapy and molecular risk maintained prognostic impact at both ASCT + 3 and ASCT + 9.
CONCLUSION
In patients with multiple myeloma, MRD status at both ASCT + 3 and ASCT + 9 is a powerful predictor of PFS and OS.
目的
微小残留病（MRD）可预测多发性骨髓瘤患者的预后，但在自体造血干细胞移植（ASCT）后维持治疗背景下，评估连续时间点的 MRD 以及 MRD 与分子风险之间的相互关系时，关于 MRD 预后影响的相关数据有限。
方法
对一项大型 III 期试验（Myeloma XI）的数据进行了分析，以确定 ASCT 后随机分配至来那度胺维持或 ASCT 后 3 个月无维持治疗的患者中，MRD 状态与无进展生存期（PFS）和总生存期（OS）之间的关系。在维持随机分组前（ASCT+3）和 6 个月后（ASCT+9），通过流式细胞术评估 MRD 状态（中位灵敏度 0.004%）。
结果
在 ASCT+3 时，750 例患者中有 475 例（63.3%）为 MRD 阴性，275 例（36.7%）为 MRD 阳性。MRD 阴性状态与 PFS 改善相关（风险比 [HR] = 0.47；95%CI，0.37 至 0.58；<0.001）和 OS（HR = 0.59；95%CI，0.40 至 0.85；=0.0046）。在 ASCT+9 时，326 例患者中有 214 例（65.6%）为 MRD 阴性，112 例（34.4%）为 MRD 阳性。MRD 阴性状态与 PFS 改善相关（HR = 0.20；95%CI，0.13 至 0.31；<0.0001）和 OS（HR = 0.33；95%CI，0.15 至 0.75；=0.0077）。将完全缓解/接近完全缓解的患者限制在研究范围内时，结果非常相似。从 ASCT+3 到 ASCT+9 的持续 MRD 阴性或 ASCT+9 时的 MRD 阴性转换与最长的 PFS/OS 相关。随机分配至来那度胺维持治疗的患者更有可能在维持随机分组前为 MRD 阳性，而在 6 个月后转为 MRD 阴性（来那度胺 30%，观察 17%）。即使对于那些达到 MRD 阴性状态的患者，高风险分子特征也会对 PFS 和 OS 产生不良影响。在对 ASCT+3 和 ASCT+9 的 MRD 状态、维持治疗和分子风险的多变量分析中，两者均保持预后影响。
结论
在多发性骨髓瘤患者中，ASCT+3 和 ASCT+9 的 MRD 状态是 PFS 和 OS 的有力预测指标。
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