Influence of patient characteristics on chimeric antigen receptor T cell therapy in B-cell acute lymphoblastic leukemia.
Influence of patient characteristics on chimeric antigen receptor T cell therapy in B-cell acute lymphoblastic leukemia.
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患者特征对 B 细胞急性淋巴细胞白血病嵌合抗原受体 T 细胞治疗的影响
DOI：
10.1038/s41467-020-19774-x
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发表时间：
2020-11-23
影响因子：
16.6
通讯作者：
Zhai Z
中科院分区：
文献类型：
--
作者：
An F;Wang H;Liu Z;Wu F;Zhang J;Tao Q;Li Y;Shen Y;Ruan Y;Zhang Q;Pan Y;Zhu W;Qin H;Wang Y;Fu Y;Feng Z;Zhai Z
CD19 特异性嵌合抗原受体 T 细胞 (CD19 CAR T) 疗法在难治性/复发性 B 细胞急性淋巴细胞白血病 (r/r B-ALL) 患者中显示出较高的缓解率。然而，长期结果和影响疗效的因素还需要进一步探讨。在此，我们报告了一项非随机 II 期临床试验（ClinicalTrials.gov 编号：NCT02735291）中 51 名复发/难治 B-ALL 患者的结果。主要结局显示总体缓解率（完全缓解，伴或不伴不完全血液学恢复）为 80.9%。次要结果显示，1 年总生存率 (OS) 和无复发生存率 (RFS) 分别为 53.0% 和 45.0%。 4级不良反应发生率为6.4%。该试验达到了预先指定的终点。进一步分析显示，除中枢神经系统（CNS）受累之外的髓外疾病（EMD）患者的缓解率最低（28.6%）。具有任何 EMD 亚型、较高 Tregs 或高风险遗传因素的患者的 OS 和 RFS 均显着低于相应的对照队列。 EMD 和较高的 Tregs 分别是 OS 和 RFS 不良的独立高风险因素。因此，这些患者特征可能会阻碍 CAR T 疗法的疗效。
CD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the long-term outcome and the factors that influence the efficacy need further exploration. Here we report the outcome of 51 r/r B-ALL patients from a non-randomized, Phase II clinical trial (ClinicalTrials.gov number: NCT02735291). The primary outcome shows that the overall remission rate (complete remission with or without incomplete hematologic recovery) is 80.9%. The secondary outcome reveals that the overall survival (OS) and relapse-free survival (RFS) rates at 1 year are 53.0 and 45.0%, respectively. The incidence of grade 4 adverse reactions is 6.4%. The trial meets pre-specified endpoints. Further analysis shows that patients with extramedullary diseases (EMDs) other than central nervous system (CNS) involvement have the lowest remission rate (28.6%). The OS and RFS in patients with any subtype of EMDs, higher Tregs, or high-risk genetic factors are all significantly lower than that in their corresponding control cohorts. EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS. Thus, these patient characteristics may hinder the efficacy of CAR T therapy.
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影响因子：
20.3
作者：
Gardner, Rebecca A.;Finney, Olivia;Jensen, Michael C.
通讯作者：
Jensen, Michael C.
影响因子：
28.2
作者：
Gust J;Hay KA;Hanafi LA;Li D;Myerson D;Gonzalez-Cuyar LF;Yeung C;Liles WC;Wurfel M;Lopez JA;Chen J;Chung D;Harju-Baker S;Özpolat T;Fink KR;Riddell SR;Maloney DG;Turtle CJ
通讯作者：
Turtle CJ
DOI：
10.1038/nrclinonc.2017.148
发表时间：
2018-01
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Neelapu SS;Tummala S;Kebriaei P;Wierda W;Gutierrez C;Locke FL;Komanduri KV;Lin Y;Jain N;Daver N;Westin J;Gulbis AM;Loghin ME;de Groot JF;Adkins S;Davis SE;Rezvani K;Hwu P;Shpall EJ
通讯作者：
Shpall EJ
影响因子：
11.4
作者：
Pan, J.;Yang, J. F.;Tong, C. R.
通讯作者：
Tong, C. R.
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M