Anti-PD-1 Therapy Enhances the Efficacy of CD30-Directed Chimeric Antigen Receptor T Cell Therapy in Patients With Relapsed/Refractory CD30+ Lymphoma.
Anti-PD-1 Therapy Enhances the Efficacy of CD30-Directed Chimeric Antigen Receptor T Cell Therapy in Patients With Relapsed/Refractory CD30+ Lymphoma.
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抗 PD-1 疗法增强 CD30 定向嵌合抗原受体 T 细胞疗法对复发/难治性 CD30 淋巴瘤患者的疗效
DOI：
10.3389/fimmu.2022.858021
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
抗CD 30 CAR-T是治疗复发性/难治性（r/r）CD 30+淋巴瘤的有效候选疗法，但存在治疗局限性，疗效有待进一步提高。在此进行了一项抗CD 30 CAR-T联合PD-1抑制剂治疗r/r CD 30+淋巴瘤的多中心II期临床试验（NCT 03196830）。在使用氟达拉滨和环磷酰胺进行淋巴细胞清除化疗后，队列1中的4名患者和队列2中的3名患者分别接受了106/kg和107/kg的CAR-T细胞，队列3中的5名患者接受了107/kg的CAR-T细胞联合抗PD-1抗体。分析了CAR-T细胞治疗的安全性和有效性。在12例患者中的4例中观察到细胞因子释放综合征（CRS），仅1例患者（患者9）发生了3级CRS，并接受了糖皮质激素和托珠单抗治疗。未观察到CAR-T相关脑病综合征。队列2和3中仅2例患者在CD 30 CAR-T细胞输注后出现明显高血浆IL-6和铁蛋白水平。总有效率（ORR）为91.7%（11/12），其中6例患者达到完全缓解（CR）（50%）。队列1和队列2中，6例患者获得缓解（85.7%），2例患者达到CR（28.6%）。在队列3中，5例无≥3级CRS的患者获得100% ORR和80% CR。中位随访时间为21.5个月（范围：3-50个月），无进展生存率和总生存率分别为45%和70%。在CAR-T治疗后获得应答的11例患者中，7例患者（63.6%）维持其应答直至随访结束。最后3例患者因疾病进展死亡。综上所述，抗PD-1抗体的组合显示出对r/r CD 30+淋巴瘤患者的CD 30 CAR-T治疗的增强作用，毒性最小。
Anti-CD30 CAR-T is a potent candidate therapy for relapsed/refractory (r/r) CD30+ lymphomas with therapy limitations, and the efficacy needed to be further improved. Herein a multi-center phase II clinical trial (NCT03196830) of anti-CD30 CAR-T treatment combined with PD-1 inhibitor in r/r CD30+ lymphoma was conducted. After a lymphocyte-depleting chemotherapy with fludarabine and cyclophosphamide, 4 patients in cohort 1 and 3 patients in cohort 2 received 106/kg and 107/kg CAR-T cells, respectively, and 5 patients in cohort 3 received 107/kg CAR-T cells combined with anti-PD-1 antibody. The safety and the efficacy of CAR-T cell therapy were analyzed. Cytokine release syndrome (CRS) was observed in 4 of 12 patients, and only 1 patient (patient 9) experienced grade 3 CRS and was treated with glucocorticoid and tocilizumab. No CAR-T-related encephalopathy syndrome was observed. Only two patients in cohorts 2 and 3 experienced obviously high plasma levels of IL-6 and ferritin after CD30 CAR-T cell infusion. The overall response rate (ORR) was 91.7% (11/12), with 6 patients achieving complete remission (CR) (50%). In cohorts 1 and 2, 6 patients got a response (85.7%), with 2 patients achieving CR (28.6%). In cohort 3, 100% ORR and 80% CR were obtained in 5 patients without ≥3 grade CRS. With a median follow-up of 21.5 months (range: 3-50 months), the progression-free survival and the overall survival rates were 45 and 70%, respectively. Of the 11 patients who got a response after CAR-T therapy, 7 patients (63.6%) maintained their response until the end of follow-up. Three patients died last because of disease progression. Taken together, the combination of anti-PD-1 antibody showed an enhancement effect on CD30 CAR-T therapy in r/r CD30+ lymphoma patients with minimal toxicities.
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DOI：
10.1056/nejmoa1707447
发表时间：
2017-12-28
期刊：
The New England journal of medicine
影响因子：
--
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
通讯作者：
Go WY
表达 CD30 嵌合抗原受体的自体 T 细胞治疗复发或难治性霍奇金淋巴瘤：开放标签 I 期试验
影响因子：
11.5
作者：
Wang, Chun-Meng;Wu, Zhi-Qiang;Han, Wei-Dong
通讯作者：
Han, Wei-Dong
影响因子：
12.8
作者：
Liu, Shuangyou;Deng, Biping;Tong, Chunrong
通讯作者：
Tong, Chunrong
影响因子：
168.9
作者：
Schmitz, N;Pfistner, B;Diehl, V
通讯作者：
Diehl, V
影响因子：
20.3
作者：
Chen, Robert;Gopal, Ajay K.;Younes, Anas
通讯作者：
Younes, Anas