Li Lian-Lian, Xia Yue-Ping, Li Qianqian, Wang Peng, Sun Ping-Ping, Wang Xing-Guang, Zhang Rui
Department of Hematology, Cangzhou People's Hospital, Cangzhou, China.
Department of Clinical Lab, Cangzhou People's Hospital, Cangzhou, China.
Front Immunol. 2024 Nov 15;15:1469251. doi: 10.3389/fimmu.2024.1469251. eCollection 2024.
Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising approach for treating relapsed/refractory (r/r) T-cell acute lymphoblastic leukemia (T-ALL). However, it is mostly used as a bridging therapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, secondary allo-HSCT is costly and associated with significantly high treatment-related mortality rate than the primary transplants. In this report, we present the case of an adult T-ALL patient who underwent CD7-targeted autologous CAR-T cell therapy that was not bridged with secondary allo-HSCT.
The adult T-ALL patient relapsed for a third time after undergoing allogeneic peripheral blood stem cell transplantation (PBSCI) and achieving the first complete remission (CR1). Therefore, the patient was administered CD7-targeted autologous CAR-T cell therapy that was not bridged with secondary allo-HSCT. Towards this, the endogenous CD7-deleted CAR (CD7-CAR7) T cells were generated using CRISPR/Cas9 gene-editing technology. However, after the first infusion, the CD7 CAR-T cells did not show significant proliferation when analyzed at two weeks and the patient became positive for peripheral measurable residual disease (MRD). Therefore, after a two-week period, an augmented dose of CAR-T cells was administered. MRD was monitored in the peripheral blood and bone marrow samples. The patient achieved complete remission and did not require targeted treatment after the completion of CD7 CAR-T-cell therapy. The current follow-up data has shown that the patient is negative for MRD and has been disease-free for more than 42 months.
The results of this case study provide evidence for the long-term efficacy of CD7-targeted autologous CAR-T-cell therapy without requiring secondary allo-HSCT in patients with r/r T-ALL that have relapsed after previous allogeneic PBSCT.
嵌合抗原受体T细胞(CAR-T)疗法已成为治疗复发/难治性(r/r)T细胞急性淋巴细胞白血病(T-ALL)的一种有前景的方法。然而,它大多用作异基因造血干细胞移植(allo-HSCT)的桥接疗法。此外,二次allo-HSCT成本高昂,且与比初次移植显著更高的治疗相关死亡率相关。在本报告中,我们介绍了一例成年T-ALL患者的病例,该患者接受了靶向CD7的自体CAR-T细胞疗法,且未进行二次allo-HSCT桥接。
该成年T-ALL患者在接受异基因外周血干细胞移植(PBSCI)并实现首次完全缓解(CR1)后第三次复发。因此,该患者接受了靶向CD7的自体CAR-T细胞疗法,且未进行二次allo-HSCT桥接。为此,使用CRISPR/Cas9基因编辑技术生成了内源性CD7缺失的CAR(CD7-CAR7)T细胞。然而,首次输注后,在两周时分析发现CD7 CAR-T细胞未显示出显著增殖,且患者外周可测量残留疾病(MRD)呈阳性。因此,两周后给予了更高剂量的CAR-T细胞。对外周血和骨髓样本进行了MRD监测。患者实现了完全缓解,在完成CD7 CAR-T细胞疗法后无需靶向治疗。目前的随访数据显示,患者MRD呈阴性,且已无病超过42个月。
本病例研究结果为既往异基因PBSCT后复发的r/r T-ALL患者在无需二次allo-HSCT的情况下,靶向CD7的自体CAR-T细胞疗法的长期疗效提供了证据。