Radiation Priming Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma With High Tumor Burden
Radiation Priming Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma With High Tumor Burden
复制标题
DOI：
10.1097/cji.0000000000000284
复制
发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Jin, Zhengming
中科院分区：
文献类型：
--
作者：
Qu, Changju;Ping, Nana;Jin, Zhengming
嵌合抗原受体T细胞（CAR-T）疗法在复发性/难治性（R/R）弥漫性大B细胞淋巴瘤（DLBCL）中表现出令人印象深刻的疗效。然而，CAR-T治疗相关的严重细胞因子释放综合征和神经毒性限制了其在高肿瘤负荷的R/R DLBCL患者中的临床应用。在这里，我们进行了一项II期临床试验，测试CAR-T疗法在R/R非霍奇金淋巴瘤患者中的疗效和毒性（NCT 03196830）。在入组的患者中，分析了10例具有高肿瘤负荷的R/R DLBCL患者。在CAR-T治疗前，4例接受强化联合化疗（C-CAR-队列），6例接受放疗（R-CAR-队列）。与C-CAR-T队列中的患者相比，R-CAR-T队列中的患者显示出更高的总缓解率（100% vs. 25%，P=0.033）和更轻的细胞因子释放综合征（0% vs. 100%，P=0.0048）和神经毒性（0% vs. 75%，P=0.033）发生率。此外，一名最初对CAR-T治疗有反应并在短期内复发的病例接受了放射治疗并实现了完全缓解，检测到的CAR-T拷贝数增加。这项研究表明，放疗是CAR-T治疗前管理R/R DLBCL患者的最佳减积方案，也是CAR-T治疗后通过增加CAR-T拷贝复发的患者的一种有希望的替代挽救治疗。
Chimeric antigen receptor T-cell (CAR-T) therapy demonstrates impressive efficacy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, CAR-T therapy-related severe cytokine release syndrome and neurological toxicity limit its clinical application in R/R DLBCL patients with high tumor burden. Here, we conducted a phase II clinical trial testing the efficacy and toxicities of CAR-T therapy in R/R non-Hodgkin lymphoma patients (NCT03196830). Among the enrolled patients, 10 R/R DLBCL patients with high tumor burden were analyzed. Before CAR-T therapy, 4 were treated with intensive combined chemotherapy (C-CAR-cohort), and 6 were exposed to radiotherapy (R-CAR-cohort). Patients in the R-CAR-T-cohort showed a higher overall response rate (100% vs. 25%, P=0.033) and less severe cytokine release syndrome (0% vs. 100%, P=0.0048) and neurotoxicity (0% vs. 75%, P=0.033) incidences than patients in the C-CAR-T-cohort. Furthermore, one case who responded to CAR-T therapy initially and who suffered a relapse shortly was exposed to radiation and achieved complete remission, with an increase in the number of CAR-T copies detected. This study demonstrates that radiotherapy is an optimal debulking regimen to managing R/R DLBCL patients before CAR-T therapy and a promising alternative salvage therapy for patients who suffer a relapse after CAR-T therapy by fuelling CAR-T copies.