文章：

建立新诊断多发性骨髓瘤患者治疗期间的可测量残留病灶动态轨迹，作为T细胞重定向疗法应用的基准

Establishing measurable residual disease trajectories for patients on treatment for newly diagnosed multiple myeloma as benchmark for deployment of T-cell redirection therapy

原文发布日期：2025-04-23

DOI: 10.1038/s41408-025-01252-6

类型: Article

开放获取: 是

英文摘要：

Autologous stem cell transplantation (ASCT) has been the prime consolidative strategy to increase the depth and duration of response in newly diagnosed multiple myeloma (NDMM), albeit with short- and long-term toxicities. Minimal residual disease (MRD) is an important early response endpoint correlating with clinically meaningful outcomes and may be used to isolate the effect of ASCT. We report the impact of ASCT on MRD burden and generate a benchmark for evaluation of novel treatments as consolidation. We collected MRD by next generation sequencing (NGS; clonoSEQ®) post induction and post-ASCT in consecutive patients (N = 330, quadruplet, N = 279; triplet, N = 51). For patients receiving quadruplets, MRD < 10−5 post-induction was 29% (MRD < 10−6 15%) increasing to 59% post-ASCT (MRD < 10−6 45%). Among patients with MRD > 10−5 post-induction, ASCT lowered the MRD burden>1 log10 for 69% patients. The use of quadruplet induction (vs. triplet) did not reduce the effect of ASCT on MRD burden. Reduction in MRD burden with ASCT was most pronounced in patients with high-risk chromosome abnormalities. This dataset provides granular data to delineate the impact of ASCT on MRD as legacy consolidative strategy in NDMM and provides an important benchmark for evaluation of efficacy of TCRT as experimental consolidative strategy.
 

摘要翻译： 

自体干细胞移植（ASCT）一直是提高新诊断多发性骨髓瘤（NDMM）治疗反应深度和持续时间的主要巩固策略，尽管其存在短期和长期毒性。微小残留病（MRD）是重要的早期反应终点，与具有临床意义的预后相关，可用于评估ASCT的独立效应。我们报告了ASCT对MRD负荷的影响，并建立了评估新型巩固治疗的基准。我们在连续患者（N=330，其中四联疗法N=279；三联疗法N=51）中通过新一代测序（NGS；clonoSEQ®）收集诱导治疗后和ASCT后的MRD数据。接受四联疗法诱导治疗的患者中，诱导后MRD<10⁻⁵的比例为29%（MRD<10⁻⁶为15%），ASCT后这一比例升至59%（MRD<10⁻⁶为45%）。在诱导后MRD>10⁻⁵的患者中，ASCT使69%患者的MRD负荷降低超过1个log₁₀。使用四联诱导方案（相较于三联方案）并未减弱ASCT对MRD负荷的影响。ASCT对MRD负荷的降低作用在高危染色体异常患者中最为显著。本数据集提供了精细数据，用以阐明ASCT作为NDMM传统巩固策略对MRD的影响，并为评估TCRT作为实验性巩固策略的疗效提供了重要基准。

原文链接：

Establishing measurable residual disease trajectories for patients on treatment for newly diagnosed multiple myeloma as benchmark for deployment of T-cell redirection therapy