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
{"title":"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","authors":"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","doi":"10.1038/s41408-025-01252-6","DOIUrl":null,"url":null,"abstract":"<p>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 (<i>N</i> = 330, quadruplet, <i>N</i> = 279; triplet, <i>N</i> = 51). For patients receiving quadruplets, MRD < 10<sup>−5</sup> post-induction was 29% (MRD < 10<sup>−6</sup> 15%) increasing to 59% post-ASCT (MRD < 10<sup>−6</sup> 45%). Among patients with MRD > 10<sup>−5</sup> post-induction, ASCT lowered the MRD burden>1 log<sub>10</sub> 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.</p><p>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.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"1 1","pages":""},"PeriodicalIF":12.9000,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Establishing measurable residual disease trajectories for patients on treatment for newly diagnosed multiple myeloma as benchmark for deployment of T-cell redirection therapy\",\"authors\":\"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\",\"doi\":\"10.1038/s41408-025-01252-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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 (<i>N</i> = 330, quadruplet, <i>N</i> = 279; triplet, <i>N</i> = 51). For patients receiving quadruplets, MRD < 10<sup>−5</sup> post-induction was 29% (MRD < 10<sup>−6</sup> 15%) increasing to 59% post-ASCT (MRD < 10<sup>−6</sup> 45%). Among patients with MRD > 10<sup>−5</sup> post-induction, ASCT lowered the MRD burden>1 log<sub>10</sub> 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.</p><p>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.</p>\",\"PeriodicalId\":8989,\"journal\":{\"name\":\"Blood Cancer Journal\",\"volume\":\"1 1\",\"pages\":\"\"},\"PeriodicalIF\":12.9000,\"publicationDate\":\"2025-04-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Blood Cancer Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41408-025-01252-6\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood Cancer Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41408-025-01252-6","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
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.
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.