Anti-CD19 CAR T-cell consolidation therapy combined with CD19+ feeding T cells and TKI for Ph+ acute lymphoblastic leukemia.
Anti-CD19 CAR T-cell consolidation therapy combined with CD19+ feeding T cells and TKI for Ph+ acute lymphoblastic leukemia.
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DOI：
10.1182/bloodadvances.2022009072
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发表时间：
2023-09-12
期刊：
影响因子：
7.5
通讯作者：
Xue, Sheng-Li
中科院分区：
文献类型：
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作者：
Chen, Li-Yun;Gong, Wen-Jie;Li, Ming-Hao;Zhou, Hai-Xia;Xu, Ming-Zhu;Qian, Chong-Sheng;Kang, Li-Qing;Xu, Nan;Yu, Zhou;Qiao, Man;Zhang, Tong-Tong;Zhang, Ling;Tian, Zheng-Long;Sun, Ai-Ning;Yu, Lei;Wu, De-Pei;Xue, Sheng-Li
CD19 CAR -t细胞巩固疗法联合CD19+ FTCs和TKI具有可管理的长期安全性。CD19 CAR - t细胞巩固治疗联合CD19+ FTCs和TKI具有较高的缓解率和持续时间。我们进行了一项单臂、开放标签、单中心的1期研究，以评估多周期序贯抗CD19嵌合抗原受体（CAR） T细胞治疗联合自体CD19+供血T细胞（FTCs）和酪氨酸激酶抑制剂（TKI）作为巩固治疗65岁以下新发ph阳性CD19+ b细胞急性淋巴细胞白血病患者的安全性和有效性。参与者接受诱导化疗和TKI全身化疗。随后，他们接受单周期CD19 CAR - t细胞输注和另外3周期CD19 CAR - t细胞和CD19+ FTC输注，然后接受TKI作为巩固治疗。CD19+ FTCs以3种不同剂量给予。报告了前15例患者的1期临床结果，其中包括2例退出试验。最常见的不良事件是细胞减少（13/13）和低γ -血红蛋白血症（12/13）。2级以上的细胞因子释放综合征、免疫效应细胞相关神经毒性综合征或4级非血液学毒性均无发生。所有13例患者均获得完全缓解，其中12例患者在数据截止时获得完全分子反应（CMR）。无复发生存率为84%，总生存率为83%，中位随访时间为27个月。cd19表达细胞的总数随着CMR率的增加而减少。CD19 CAR - T细胞存活长达40个月，而CD19+ FTCs在最后一次输注后3个月在8例患者中消失。这些发现可以为无同种异体造血干细胞的巩固模式的发展奠定基础。该试验在www.clinicaltrials.gov注册为#NCT03984968。
CD19 CAR T-cell consolidation therapy combined with CD19+ FTCs and TKI had a manageable long-term safety profile. CD19 CAR T-cell consolidation therapy combined with CD19+ FTCs and TKI yielded a high response rate and duration. We conducted a single-arm, open-label, single-center phase 1 study to assess the safety and efficacy of multicycle-sequential anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in combination with autologous CD19+ feeding T cells (FTCs) and tyrosine kinase inhibitor (TKI) as consolidation therapy in patients under the age of 65 years with de novo Ph-positive CD19+ B-cell acute lymphoblastic leukemia. Participants were given induction chemotherapy as well as systemic chemotherapy with TKI. Afterward, they received a single cycle of CD19 CAR T-cell infusion and another 3 cycles of CD19 CAR T-cell and CD19+ FTC infusions, followed by TKI as consolidation therapy. CD19+ FTCs were given at 3 different doses. The phase 1 results of the first 15 patients, including 2 withdrawals, are presented. The most common adverse events were cytopenia (13/13) and hypogammaglobinemia (12/13). There was no incidence of cytokine release syndrome above grade 2 or immune effector cell-associated neurotoxicity syndrome or grade 4 nonhematological toxicities. All 13 patients achieved complete remission, including 12 patients with a complete molecular response (CMR) at the data cutoff. The relapse-free survival was 84%, and the overall survival was 83% with a median follow-up of 27 months. The total number of CD19-expressing cells decreased with an increasing CMR rate. CD19 CAR T cells survived for up to 40 months, whereas CD19+ FTCs vanished in 8 patients 3 months after the last infusion. These findings could form the basis for the development of an allo-HSCT–free consolidation paradigm. This trial was registered at www.clinicaltrials.gov as #NCT03984968.
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影响因子：
15.9
作者：
Finney, Olivia C.;Brakke, Hannah;Jensen, Michael C.
通讯作者：
Jensen, Michael C.
影响因子：
20.3
作者：
Mueller, Karen Thudium;Maude, Shannon L.;Lacey, Simon F.
通讯作者：
Lacey, Simon F.
影响因子：
10.1
作者：
Daver, Naval;Thomas, Deborah;O'Brien, Susan
通讯作者：
O'Brien, Susan
影响因子：
20.3
作者：
Gauthier, Jordan;Bezerra, Evandro D.;Turtle, Cameron J.
通讯作者：
Turtle, Cameron J.
DOI：
10.1056/nejmoa1709919
发表时间：
2018-02-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
Park JH;Rivière I;Gonen M;Wang X;Sénéchal B;Curran KJ;Sauter C;Wang Y;Santomasso B;Mead E;Roshal M;Maslak P;Davila M;Brentjens RJ;Sadelain M
通讯作者：
Sadelain M