Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma.
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DOI：
10.1056/nejmoa1707447
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发表时间：
2017-12-28
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影响因子：
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通讯作者：
Go WY
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作者：
Neelapu SS;Locke FL;Bartlett NL;Lekakis LJ;Miklos DB;Jacobson CA;Braunschweig I;Oluwole OO;Siddiqi T;Lin Y;Timmerman JM;Stiff PJ;Friedberg JW;Flinn IW;Goy A;Hill BT;Smith MR;Deol A;Farooq U;McSweeney P;Munoz J;Avivi I;Castro JE;Westin JR;Chavez JC;Ghobadi A;Komanduri KV;Levy R;Jacobsen ED;Witzig TE;Reagan P;Bot A;Rossi J;Navale L;Jiang Y;Aycock J;Elias M;Chang D;Wiezorek J;Go WY
在第1阶段试验中，一种自体抗CD19嵌合抗原受体（CAR）T细胞疗法a toxabtagene cileoleucel（Axi-Cel）显示了常规治疗失败后难治性大B细胞淋巴瘤患者的效率。
在这项多中心2期试验中，我们招募了111例弥漫性大B细胞淋巴瘤，原发性纵隔B细胞淋巴瘤或转化的卵泡淋巴瘤，患有难治性疾病的卵泡淋巴瘤接受了预先的治疗。 -CD19的CAR T细胞每千克的体重接受低剂量环磷有剂和氟达拉酸酯的条件方案包括整体生存，安全和生物标志物评估。
在111名被招募的患者中，Axi-Cel成功制造了110（99％），并施用101例（91％）。 - 15.4个月，有42％的患者继续反应，40％的患者持续了整体响应。治疗是中性政（78％的患者），贫血（43％）和血小板减少症（分别为38％）。三名患者在治疗中死亡。
在这项多中心研究中，接受AXI-CEL的CAR T细胞治疗的难治性大B细胞淋巴瘤具有较高的耐用反应，其安全性包括骨髓抑制作用，细胞因子释放综合征和神经系统风筝制药和白血病和淋巴瘤协会疗法加速计划； Zuma-1临床。
In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments. Among the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%). The objective response rate was 82%, and the complete response rate was 54%.With a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a complete response. The overall rate of survival at 18 months was 52%. The most common adverse events of grade 3 or higher during treatment were neutropenia (in 78% of the patients), anemia (in 43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. Three of the patients died during treatment. Higher CAR T-cell levels in blood were associated with response. In this multicenter study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events. (Funded by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program; ZUMA-1 ClinicalTrials.gov number, NCT02348216.)