Xue YuanBo, Lai Xun, Li RuiLei, Ge ChunLei, Zeng BaoZhen, Li Zhen, Fu QiaoFen, Zhao LiuFang, Dong SuWei, Yang JinYan, Guo JiYin, Meng QingYin, Tan QingHua, Li ZhenHui, Ding HaiYan, Zhang YanLei, Liu ShaoHui, Chang Alex H, Yao Hong, Luo RongCheng
Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University Guangdong, Guangzhou, China.
Cancer Biotherapy Center, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, China.
Front Oncol. 2021 Feb 2;10:607362. doi: 10.3389/fonc.2020.607362. eCollection 2020.
In clinical applications of CAR T-cell therapy, life-threatening adverse events including cytokine release syndrome and neurotoxicity can lead to treatment failure. Outcomes of patients treated with anti-CD30 CAR T- cell have been disappointing in relapsing/refractory (r/r) classical Hodgkin's Lymphoma (cHL).
In order to understand the applicable population of multiple CAR T-cell therapy, we examined the expression of CD19, CD20, and CD30 by immunohistochemistry (IHC) in 38 paraffin-embedded specimens of cHL. In the past two years, we found only one patient with cHL who is eligible for combined anti-CD19 and CD30 CAR T-cell treatment. This patient's baseline characteristics were prone to severe adverse events. We treated this patient with low doses and multiple infusions of anti-CD19 and CD30 CAR T-cell.
The positive expression of CD19 + CD30 in Reed-Sternberg (RS) cells is approximately 5.2% (2/38). The patient we treated with combined anti-CD19 and CD30 CAR T-cell did not experience severe adverse events related to CAR T-cell therapy and received long term progression-free survival (PFS).
For high risk r/r cHL patients, low doses of CAR T-cell used over different days at different times might be safe and effective. More clinical trials are warranted for CD19 and CD30 CAR T-cell combination therapy.
在嵌合抗原受体(CAR)T细胞疗法的临床应用中,包括细胞因子释放综合征和神经毒性在内的危及生命的不良事件可能导致治疗失败。抗CD30 CAR T细胞治疗复发/难治性(r/r)经典型霍奇金淋巴瘤(cHL)患者的疗效一直令人失望。
为了解多种CAR T细胞疗法的适用人群,我们通过免疫组织化学(IHC)检测了38例cHL石蜡包埋标本中CD19、CD20和CD30的表达。在过去两年中,我们仅发现1例符合抗CD19和CD30 CAR T细胞联合治疗条件的cHL患者。该患者的基线特征易发生严重不良事件。我们对该患者采用低剂量、多次输注抗CD19和CD30 CAR T细胞进行治疗。
里德-斯腾伯格(RS)细胞中CD19+CD30的阳性表达约为5.2%(2/38)。我们用抗CD19和CD30 CAR T细胞联合治疗的患者未发生与CAR T细胞疗法相关的严重不良事件,并获得了长期无进展生存(PFS)。
对于高危r/r cHL患者,在不同时间分不同天数使用低剂量CAR T细胞可能是安全有效的。抗CD19和CD30 CAR T细胞联合疗法需要更多的临床试验。