The press release below was prepared by the American Association for 癌症研究. 查看原文 在大发娱乐.
与流式细胞术和监测b细胞发育不全相比，新一代微小残留疾病测序具有高度敏感性和准确性
PHILADELPHIA – In pediatric 和 young adult 病人 with 急性淋巴细胞白血病 (ALL) treated with tisagenlecleucel (Kymriah), 基于DNA测序的3至12个月间残留疾病检测准确地确定了所有最终会复发的患者, while other methods were less predictive, 根据… 研究 发表在 发现血癌的杂志 American Association for 癌症研究.
"This is the first paper to show an approach that identifies markers of relapse that are very specific, allowing clinicians to add additional therapy prior to relapse that will prevent it,” 迈克尔·普尔斯弗，医学博士, 该研究的主要作者，儿科教授，山间初级儿童医院和犹他大学亨茨曼癌症研究所儿科血液学和肿瘤学部门主任.
Tisagenlecleucel是一种嵌合抗原受体T细胞（CAR-T）疗法，是一种收集患者自身T细胞的疗法, reprogrammed to target a protein called CD19 that is expressed on the surface of cancer cells, returned to the patient to fight ALL 和 lymphoma. Pulsipher说，超过80%的ALL患者接受了tisagenlecleucel治疗后，病情完全缓解.
然而, around half of 病人 who experience remission eventually relapse 和 require additional treatment, 比如骨髓移植. 准确预测复发可以让需要移植的患者在疾病真正复发之前就开始手术.
Because the CD19 receptor is also expressed on normal B cells, treatment causes B-cell aplasia—the depletion of a patient’s B cells. “大发娱乐目前对大发娱乐提供tisagenleclear的中心的建议是每月跟踪血液中的B细胞, 使用标准测试, as a way to predict 病人 at higher risk of relapse,” Stephan Grupp，医学博士，博士, 该研究的资深作者，儿科教授，费城儿童医院和宾夕法尼亚大学细胞治疗和移植主任. "Monitoring B-cell aplasia is not ideal because it only picks up part of the relapse risk." He noted that recurrence can sometimes occur in the absence of B-cell recovery, in the form of tumor cells that do not express CD19 和 can t在大发娱乐fore evade functional CAR-T cells.
“大发娱乐的患者和家属的一个关键目标不仅是确定哪些患者复发风险增加，需要进一步治疗, 但也可以识别那些可能不需要进一步治疗（如移植）的长期受益患者,格鲁普说.
Liquid biopsies that investigate markers in the blood or bone marrow have increased in popularity, but these methods have not been directly compared. 在这项研究中, Pulsipher和他的同事研究了流式细胞术（一种检测细胞表面蛋白质的技术）和下一代DNA测序最小残留病（NGS-MRD）监测的预测价值, using blood 和 bone marrow samples collected from the 艾丽亚娜一直 和 旗 phase II clinical trials at one, 三个, 六个, 九个, 12 months after tisagenlecleucel infusion. 流式细胞术, cells were analyzed for the presence of CD9, CD10, CD13, CD19, CD20, CD22, CD33, CD34, CD38, CD45, CD58, CD66c, 和CD123. For NGS, the gene sequences of IgH, IgK, IgL were analyzed for rearrangements 和 translocations.
研究人员发现，, while flow cytometry could detect approximately one cancer cell per 10,000个血细胞, NGS-MRD要敏感得多, with the ability to detect one cancer cell per 1 to 10 million blood cells, depending on the number of cells in the sample. This resulted in 131 percent more positive samples detected via NGS-MRD compared with flow cytometry.
NGS-MRD of bone marrow samples was more accurate in predicting relapse than flow cytometry. Of 病人 with any detectable disease DNA at 三个 or 六个 months post-infusion, 100 percent experienced either a relapse or progression to another therapy, with the exception of one patient lost to follow-up. NGS-MRD detection was also able to find those at risk well in advance of relapse. NGS-MRD呈最低水平阳性的患者在阳性检测后的中位复发时间为168天, the assay detected 100 percent of the relapses. 相比之下, flow cytometry was positive at a median 52 days prior to relapse 和 missed 50 percent of the relapses.
这些数据表明，更敏感的NGS测量方法在疾病复发前有足够的提前期来检测疾病，以便重复采样和/或协调治疗干预措施, Pulsipher说.
NGS-MRD was also more accurate than B-cell aplasia at predicting relapse. 治疗后3个月, B-cell recovery was not predictive of recurrence, while 病人 with a positive NGS sample had a 12-fold higher risk of recurrence.
Pulsipher recommended that NGS-MRD should complement monitoring of B-cell aplasia, 而不是替换它, 然而. 他解释说, 对一些病人来说, 28 days may not be sufficient for CAR-T cells to rid the body of all primary disease, meaning these 病人 may test positive at one month but negative at 三个 months. T在大发娱乐fore, the predictive value of NGS-MRD was lower at the one-month time point, reflecting a 4.87-fold increased risk for positive 病人. B-cell recovery had a higher predictive value early after treatment, with positive 病人 experiencing a 3.复发率高出33倍, which Pulsipher noted was insufficient on its own, due to the method’s inability to identify tumor cells lacking the CD19 receptor.
整体, Pulsipher及其同事建议在治疗后6个月内失去b细胞发育不全或在治疗后一年内出现ngs - mrd阳性骨髓疾病的患者接受额外治疗以防止复发.
Pulsipher指出，他的团队目前正在进行一项前瞻性临床试验，根据NGS-MRD测试的测量结果，在患者复发之前确定干预的可行性.
在一个 评论 与这项研究相关的是， Sara Ghorashian，医学博士, 杰克·巴特拉姆，BM BCh, pediatric hematologists at the Great Ormond Street Hospital for Children in London, 写了, “到目前为止，还没有系统地探索使用分子MRD评估后的治疗tisagenlecleucel的报告. T在大发娱乐 is utility in the data Pulsipher et al. 大发娱乐提供, 将[流式细胞术]与NGS-MRD进行比较，而后者已经建立了更高的灵敏度, 但重要的是, 同时探索阳性的最佳阈值和从阳性结果到复发的提前时间，以获得复发风险的最佳生物标志物."
他们补充道, “从这些数据中可以清楚地看出，NGS-MRD有可能成为输注tisagenlecleel后复发的有力预测指标, 把这些数据向前推进, the wider applicability of this approach in a multi-centre prospective validation is needed.
本研究的局限性包括NGS-MRD评估的样本数量相对较少（不到400个）。, 尤其是从外周血中, the fact that samples were available for relatively few time points (one, 三个, 六个, 九个, 和12个月).
This 研究 was funded by the Novartis Pharmaceuticals Corporation. Pulsipher has participated in steering committees for the 旗 和 艾丽亚娜一直 trials included in this work; served on advisory boards for Mesoblast, 碧玉疗法, Novartis; participated in educational activities for Miltenyi Biotec, 自适应生物技术, Novartis; 和 received research support from Miltenyi Biotec 和 自适应生物技术. Grupp chaired the 研究督导委员会 for the 旗 和 艾丽亚娜一直 trials; has received research 和/or clinical trial support from Novartis, Servier实验室, 顶点药品, Kite Pharma; 和 has participated in consulting, 研究督导委员会, or scientific/clinical advisory boards for Novartis, 隐性基因疗法, 细胞生物医学小组, 公司., Cellectis, Adaptimmune疗法, 尤里卡疗法, TCR2疗法, 朱诺疗法, 葛兰素史克公司, 顶点药品, CRISPR疗法, 和罗氏制药公司.
# # #
有关AACR的信息，请访问 快速的事实.
About the American Association for 癌症研究
成立于1907年, 美国癌症研究协会（AACR）是世界上第一个也是最大的专业组织，致力于推进癌症研究，并以预防和治疗癌症为使命. AACR成员包括49个,000例实验室, 平移, clinical researchers; population scientists; other health care professionals; 和 patient advocates residing in 128 countries. AACR汇集了癌症界的所有专业知识，以加速预防工作的进展, 诊断, 通过每年召开30多个会议和教育研讨会——其中最大的是AACR年会, 超过74个,000 attendees for the 2020 virtual meetings 和 more than 22,500 attendees for past in-person meetings. 除了, the AACR publishes ten prestigious, peer-reviewed scientific journals 和 a magazine for cancer survivors, 病人, 以及他们的看护人. AACR直接资助有价值的研究，并与许多癌症组织合作. As the Scientific Partner of St和 Up To Cancer, the AACR 大发娱乐提供s expert peer review, 资金管理, 对团队科学和个人研究人员在癌症研究中的资助进行科学监督，这些研究可能会在短期内为患者带来好处. AACR积极与立法者和其他决策者就癌症研究和相关生物医学科学在拯救癌症生命方面的价值进行沟通. For more information about the AACR, visit www.AACR.org.