A phase I study of anti-BCMA CAR T cell therapy in relapsed/refractory multiple myeloma and plasma cell leukemia.
A phase I study of anti-BCMA CAR T cell therapy in relapsed/refractory multiple myeloma and plasma cell leukemia.
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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
DOI：
10.1002/ctm2.346
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发表时间：
2021-03
影响因子：
10.6
通讯作者：
Zhou J
中科院分区：
文献类型：
--
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
复发性/难治性（R/R）多发性骨髓瘤（MM）和原发性浆细胞白血病（PCL）患者预后不良且无有效治疗。本研究旨在评估新型抗B-细胞成熟抗原（BCMA）嵌合抗原受体（CAR）T细胞在R/R MM和PCL中的安全性和初步疗效。在2017年2月22日至2018年6月25日期间，28名R/R和2名R/R原发性PCL患者接受了中位剂量11.2 × 106 CAR+细胞/kg。受试者对蛋白酶体抑制剂和/或免疫调节剂难治。给予氟达拉滨和环磷酰胺作为淋巴细胞清除化疗。报告了接受抗BCMA CAR T细胞输注的这30名连续患者的结果。这些患者接受了中位值为4线的既往治疗。共记录了44种不同类型的不良事件，血液学毒性反应是治疗期间任何级别最常见的事件。血液学毒性作用也是最常见的3级或以上事件。共有29例患者（96.7%）出现细胞因子释放综合征，其中24例患者（80%）为1级或2级，5例患者（16.7%）为3级。仅1例患者（3.3%）发生神经毒性反应，为1级。客观缓解率为90%，完全缓解率为43.3%。中位随访时间为12.6个月，中位无进展生存期（PFS）和总生存期分别为5.2个月和14.0个月。两个原发性PCL中的一个实现了完全缓解，PFS为307天。其他患者获得了非常好的部分缓解，PFS为117天。抗BCMA CAR T细胞治疗在R/R多发性骨髓瘤中是安全且高度活性的。我们报告了输注抗BCMA CAR T细胞治疗复发性/难治性恶性浆细胞疾病的疗效和安全性。抗BCMA CAR T细胞疗法在复发/难治性多发性骨髓瘤中表现出更好的安全性和初步疗效。复发性/难治性原发性浆细胞白血病可能受益于CAR T细胞治疗，尽管反应持续时间很短。
Relapsed/refractory (R/R) multiple myeloma (MM) patients and primary plasma cell leukemia (PCL) have an unfavorable prognosis and no effective treatment. This study was designed to assess the safety and preliminary efficacy of a novel anti‐B‐cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell in R/R MM and PCL. Between February 22, 2017, and June 25, 2018, 28 R/R and two R/R primary PCL patients received a median dose of 11.2 × 106 CAR+ cells/kg. The subjects were refractory to a proteasome inhibitor and/or an immunomodulatory agent. Fludarabine and cyclophosphamide were given as lymphodepletion chemotherapy. Results for these 30 consecutive patients who received an anti‐BCMA CAR T cell infusion are reported. The patients had received a median of four prior lines of therapy. A total of 44 different types of adverse events were recorded, and hematologic toxic effects were the most common events of any grade during treatment. Hematologic toxic effects were also the most common events of grade 3 or higher. A total of 29 patients (96.7%) had cytokine release syndrome, which was of grade 1 or 2 in 24 patients (80%) and grade 3 in five patients (16.7%). Neurologic toxic effects only occurred in one patient (3.3%) and were of grade 1. The objective response rate was 90%, and the complete response rate was 43.3%. With a median follow‐up of 12.6 months, the median progression‐free survival (PFS) and overall survival were 5.2 months and 14.0 months. One of the two primary PCL achieved a complete response with a PFS of 307 days. The other patients achieved a very good partial response with a PFS of 117 days. Anti‐BCMA CAR T cell treatment is safe and highly active in R/R multiple myeloma. We report the efficacy and safety of the infusion of anti‐BCMA CAR T cell treatment in with relapsed/refractory malignant plasma cell disease. Anti‐BCMA CAR T cell therapy exerted better safety and preliminary efficacy in relapsed/refractory multiple myeloma. Relapsed/refractory primary plasma cell leukemia may benefit from CAR T Cell treatment, although the duration of response is short.
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影响因子：
11.4
作者：
Kumar SK;Lee JH;Lahuerta JJ;Morgan G;Richardson PG;Crowley J;Haessler J;Feather J;Hoering A;Moreau P;LeLeu X;Hulin C;Klein SK;Sonneveld P;Siegel D;Bladé J;Goldschmidt H;Jagannath S;Miguel JS;Orlowski R;Palumbo A;Sezer O;Rajkumar SV;Durie BG;International Myeloma Working Group
通讯作者：
International Myeloma Working Group
影响因子：
11.4
作者：
Chim CS;Kumar SK;Orlowski RZ;Cook G;Richardson PG;Gertz MA;Giralt S;Mateos MV;Leleu X;Anderson KC
通讯作者：
Anderson KC
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：
Gandhi, Ujjawal H.;Cornell, Robert F.;Costa, Luciano J.
通讯作者：
Costa, Luciano J.
DOI：
10.1016/s0889-8588(05)70125-8
发表时间：
1999-12-01
影响因子：
2.4
作者：
Bladé, J;Kyle, RA
通讯作者：
Kyle, RA