肿瘤细胞治疗研究
英文原题：CD19 CAR T cell therapy BY19 for pediatric and adult patients with relapsed or refractory B cell neoplasms in Belarus: Phase 1 trial.
细胞因子释放综合征（CRS）发生在67%的输注中，大多为1-2级，重度CRS占19%。
在许多发展中国家，获得嵌合抗原受体（CAR）T细胞治疗的机会仍然有限。我们在两个白俄罗斯中心开展了一项单臂、开放标签、1期试验（NCT05333302），评估一种院内生产的CD19 CAR T细胞产品（BY19）在复发/难治性B细胞恶性肿瘤儿童和成人患者中的疗效。淋巴细胞清除方案包括氟达拉滨/环磷酰胺，联合或不联合地西他滨。23例患者接受了治疗：17例B细胞急性淋巴细胞白血病，1例慢性淋巴细胞白血病，5例非霍奇金淋巴瘤。细胞因子释放综合征（CRS）发生于67%的输注中，大多为1-2级，重度CRS占19%。免疫效应细胞相关神经毒性发生于44%，重度病例占18.5%。总体缓解率为80%（16/20可评估），第28天75%达到完全缓解。中位无进展生存期（PFS）为23个月；12个月PFS在淋巴瘤中为83.3%，在B细胞急性淋巴细胞白血病（B-ALL）中为48.3%。较高的C max水平倾向于与更好的缓解率相关（p = 0.0416）；然而，未观察到PFS方面的明显优势。BY19的安全性和有效性特征与已获批的CD19 CAR T细胞产品相当。本研究强调了本地化CAR T细胞生产的转化潜力，可扩大先进免疫治疗在全球的可及性，尤其是在中等收入国家。含地西他滨的淋巴细胞清除显示出潜在获益，值得进一步研究。
Access to chimeric antigen receptor (CAR) T cell therapy remains limited in many developing countries. We conducted a single-arm, open-label, phase 1 trial (NCT05333302) at two Belarusian centers, evaluating an in-house manufactured CD19 CAR T cell product (BY19) in pediatric and adult patients with relapsed/refractory B cell malignancies. Lymphodepletion included fludarabine/cyclophosphamide, with or without decitabine. Twenty-three patients received therapy: seventeen B cell acute lymphoblastic leukemia, one chronic lymphocytic leukemia, and five non-Hodgkin lymphomas. Cytokine release syndrome (CRS) occurred in 67% of infusions, mostly grade 1-2, with severe CRS in 19%. Immune effector cell-associated neurotoxicity occurred in 44%, with severe cases in 18.5%. The overall response rate was 80% (16/20 evaluable), with complete remission achieved in 75% at day 28. Median progression-free survival (PFS) was 23 months; 12-month PFS was 83.3% in lymphoma and 48.3% in B cell acute lymphoblastic leukemia (B-ALL). Higher C max levels tended to correlate with better response rates ( p = 0.0416); however, no clear advantage in PFS was observed. BY19's safety and efficacy profiles were comparable to approved CD19 CAR T cell products. This study underscores the translational potential of localized CAR T cell manufacturing to expand global access to advanced immunotherapies, especially in middle-income countries. Decitabine-containing lymphodepletion showed potential benefit and warrants further study.
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