肿瘤细胞治疗研究
英文原题：Long-term Complete Remission of Decitabine-Primed Tandem CD19/CD22 CAR-T Therapy with PD-1 and BTK Inhibitors Maintenance in a Refractory Primary Central Nervous System Lymphoma Patient.
本研究表明在 PCNSL 治疗中具有巨大潜力，并为正在进行的临床研究提供了展望。
原发性中枢神经系统淋巴瘤（PCNSL）是一种罕见且侵袭性强的非霍奇金淋巴瘤，累及脑、眼、脑脊液或脊髓，无全身受累。与系统性弥漫大B细胞淋巴瘤患者相比，PCNSL患者的预后更差。鉴于严重免疫效应细胞相关神经毒性综合征（ICANS）可能带来的死亡风险，PCNSL患者最初被排除在大多数涉及CAR-T 细胞治疗的临床试验之外。在此，我们首次报道对一例多线耐药的难治性PCNSL患者应用地西他滨预处理的串联CD19/CD22双靶点CAR-T治疗，并以程序性细胞死亡-1（PD-1）和布鲁顿酪氨酸激酶（BTK）抑制剂维持治疗，该患者在35个月的随访期内持续保持完全缓解（CR）。本病例代表了首例多线耐药难治性PCNSL患者在接受串联CD19/CD22双特异性CAR-T治疗并继以PD-1和BTK抑制剂维持治疗后，实现长期CR且未诱发ICANS的成功治疗。本研究显示了治疗PCNSL的巨大潜力，并为正在进行的临床研究提供了展望。
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin's lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton's tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.
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