Anti-BCMA CAR-T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease: A Single Center Analysis of Two Clinical Trials.
Anti-BCMA CAR-T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease: A Single Center Analysis of Two Clinical Trials.
复制标题
抗 BCMA CAR-T 细胞治疗患有髓外疾病的复发/难治性多发性骨髓瘤患者：两项临床试验的单中心分析
DOI：
10.3389/fimmu.2021.755866
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Que Y;Xu M;Xu Y;Almeida VDF;Zhu L;Wang Z;Wang Y;Liu X;Jiang L;Wang D;Li C;Zhou J
复发/难治性多发性骨髓瘤（RRMM）患者的髓外病变的预后显着差。髓外多发性骨髓瘤（EMM）患者从传统药物中获益有限。抗B细胞成熟抗原（BCMA）嵌合抗原受体（CAR）T细胞疗法似乎是治疗RRMM患者的一种有前途的方法。然而，很少有临床研究是为EMM设计的。我们的研究旨在比较和评估抗BCMA CAR-T细胞疗法在EMM和非EMM中的安全性、有效性和药代动力学。审查并总结了已发表的抗BCMA CAR-T临床试验的结果，其中可获得EMM患者的原始数据。分析了在我们的临床中心进行的两项试验，并提供了详细的数据。根据已发表的抗BCMA CAR-T临床试验，EMM的ORR范围为57%至100%，完全缓解（CR）率为29%至60%。在2017年2月22日至2019年9月26日期间，共有61例受试者（EMM 25例;非EMM 36例）接受了抗BCMA CAR-T细胞输注。数据截止日期为2021年4月1日。EMM组和非EMM组在不良事件（AE）（包括细胞因子释放综合征（CRS））方面无统计学差异。两组中最常见的≥ 3级AE为血液学毒性。两组客观缓解率（ORR）和≥完全缓解率（CR）差异无统计学意义。然而，EMM组的≥ CR率低于接受全人抗BCMA CAR-T细胞治疗的非EMM组（p = 0.026）。EMM组和非EMM组的中位无进展生存期（PFS）分别为121天和361天（p = 0.001）。EMM组和非EMM组的中位总生存期（OS）分别为248天和1024天（p = 0.005）。EMM组的Cmax和AUC 0 - 28 d低于非EMM组（Cmax，p = 0.016; AUC 0 - 28 d，p = 0.016）。在接受抗BCMA CAR-T细胞治疗的RRMM患者中，髓外疾病是PFS（风险比，2.576; 95% CI，1.343至4.941; p = 0.004）和OS（风险比，2.312; 95% CI，1.165至4.592; p = 0.017）的独立预后风险因素。根据我们的结果，EMM患者可以从两种抗BCMA CAR产品中获益，尽管与非EMM患者相比，他们的PFS和OS较短。 ，标识符ChiCTR-OPC-16009113和ChiCTR 1800018137。
The prognosis of relapsed/refractory multiple myeloma (RRMM) patients with the extramedullary disease was significantly poor. Extramedullary multiple myeloma (EMM) patients gained limited benefits from traditional drugs. Anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy seems to be a promising approach to treat RRMM patients. However, very few clinical studies are designed for EMM. Our study aimed to compare and assess the safety, efficacy, and pharmacokinetics of anti-BCMA CAR-T cell therapy in EMM and non-EMM. The results from published anti-BCMA CAR-T clinical trials, in which raw data of EMM patients were available, were reviewed and summarized. Two trials conducted in our clinical centers were analyzed and presented with detailed data. According to published anti-BCMA CAR-T clinical trials, the ORR of EMM ranged from 57% to 100%, with the complete remission (CR) rate of 29% to 60%. Between February 22, 2017, and September 26, 2019, a total of 61 subjects (EMM 25; non-EMM 36) received anti-BCMA CAR-T cell infusion. The data-cutoff date was April 1, 2021. There were no statistical differences between EMM and non-EMM groups in adverse events (AEs), including cytokine release syndrome (CRS). The most common AEs of grade ≥ 3 in both groups were hematologic toxicities. There was no significant difference in the objective response rate (ORR) and ≥ complete remission (CR) rate between both groups. However, the ≥ CR rate of the EMM group was lower than the non-EMM group receiving the fully human anti-BCMA CAR-T cell therapy (p = 0.026). The median progression-free survival (PFS) for EMM and the non-EMM group was 121 days and 361 days, respectively (p = 0.001). The median overall survival (OS) for EMM and the non-EMM group was 248 days and 1024 days, respectively (p = 0.005). The Cmax and AUC0-28d for EMM group were lower than non-EMM group (Cmax, p = 0.016; AUC0-28d, p = 0.016). Extramedullary disease was an independent prognostic risk factor for PFS (hazard ratio, 2.576; 95% CI, 1.343 to 4.941; p = 0.004) and OS (hazard ratio, 2.312; 95% CI, 1.165 to 4.592; p = 0.017) in RRMM patients receiving anti-BCMA CAR-T cell therapy. Based on our results, EMM patients could benefit from the two anti-BCMA CAR products, although they had a shorter PFS and OS compared with non-EMM patients. , identifier ChiCTR-OPC-16009113 and ChiCTR1800018137.
登录
查看更多内容
DOI：
10.1186/s12964-016-0160-z
发表时间：
2017-01-05
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Catakovic K;Klieser E;Neureiter D;Geisberger R
通讯作者：
Geisberger R
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：
3.1
作者：
Pick, Marjorie;Vainstein, Vladimir;Gatt, Moshe E.
通讯作者：
Gatt, Moshe E.
抗 BCMA CAR T 细胞治疗复发/难治性多发性骨髓瘤和浆细胞白血病的 I 期研究
影响因子：
10.6
作者：
Li C;Cao W;Que Y;Wang Q;Xiao Y;Gu C;Wang D;Wang J;Jiang L;Xu H;Xu J;Zhou X;Hong Z;Wang N;Huang L;Zhang S;Chen L;Mao X;Xiao M;Zhang W;Meng L;Cao Y;Zhang T;Li J;Zhou J
通讯作者：
Zhou J
影响因子：
4.3
作者：
Lee, Daniel W.;Santomasso, Bianca D.;Neelapu, Sattva S.
通讯作者：
Neelapu, Sattva S.