为新诊断的多发性骨髓瘤患者建立可测量的残留疾病轨迹,作为部署t细胞重定向治疗的基准

IF 12.9 1区 医学 Q1 HEMATOLOGY
Susan Bal, Tylan Magnusson, Gayathri Ravi, Smith Giri, Kelly Godby, Binod Dhakal, Natalie S. Callander, Rebecca W. Silbermann, Bhagirathbhai Dholaria, Vishnu B. Reddy, Luciano J. Costa
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引用次数: 0

摘要

自体干细胞移植(ASCT)一直是增加新诊断的多发性骨髓瘤(NDMM)的深度和持续时间的主要巩固策略,尽管具有短期和长期的毒性。微小残留病(MRD)是一个重要的早期反应终点,与临床有意义的结果相关,可用于分离ASCT的效果。我们报告了ASCT对MRD负担的影响,并产生了评估新治疗方法作为巩固的基准。我们通过下一代测序(NGS)收集MRD;clonoSEQ®)诱导后和asct后连续患者(N = 330,四联体,N = 279;三联体,N = 51)。对于接受四胞胎的患者,诱导后的MRD <; 10−5为29% (MRD <; 10−6为15%),asct后增加到59% (MRD <; 10−6为45%)。在诱导后MRD为10−5的患者中,ASCT降低了69%患者的MRD负担1 log10。使用四联体诱导(相对于三联体)并没有降低ASCT对MRD负担的影响。ASCT对MRD负担的减轻在高危染色体异常患者中最为明显。该数据集提供了细粒度数据来描述ASCT作为NDMM遗留巩固策略对MRD的影响,并为评估TCRT作为实验性巩固策略的有效性提供了重要基准。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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.

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来源期刊
CiteScore
16.70
自引率
2.30%
发文量
153
审稿时长
>12 weeks
期刊介绍: Blood Cancer Journal is dedicated to publishing high-quality articles related to hematologic malignancies and related disorders. The journal welcomes submissions of original research, reviews, guidelines, and letters that are deemed to have a significant impact in the field. While the journal covers a wide range of topics, it particularly focuses on areas such as: Preclinical studies of new compounds, especially those that provide mechanistic insights Clinical trials and observations Reviews related to new drugs and current management of hematologic malignancies Novel observations related to new mutations, molecular pathways, and tumor genomics Blood Cancer Journal offers a forum for expedited publication of novel observations regarding new mutations or altered pathways.
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