肿瘤细胞治疗研究
英文原题：Anbalcabtagene autoleucel (PD-1 and TIGIT knockdown CD19 CAR-T) for relapsed/refractory large B-cell lymphoma (CRC01-01).
在 II 期研究中，79 例患者接受了 Anbal-cel 治疗，并在 73 例患者中评估了疗效。
Anbalcabtagene autoleucel（Anbal-cel）是一种靶向 CD19 的 CAR-T 细胞疗法，通过同时敲低 PD-1 和 TIGIT 增强抗肿瘤功能及持久性。我们报告一项在复发或难治性大 B 细胞淋巴瘤（LBCL）患者中开展的 I/II 期研究结果。II 期中 79 例患者接受 Anbal-cel 治疗，其中 73 例纳入疗效评估。完全缓解（CR）率为 67.1%，部分缓解（PR）率为 8.2%。中位无进展生存期（PFS）为 6.04 个月（95% CI 4.34–16.46），6、12 和 18 个月 PFS 率分别为 50.9%、41.1% 和 35.2%。中位总生存期（OS）尚未达到；12 和 18 个月 OS 率分别为 66.6% 和 57.3%。应答者 CAR-T 细胞扩增显著高于未应答者（中位 Cmax：20,403 对 8,580 copies/μg）。根据 6 个月时持续 CR，将患者分为长期应答（LR）组和非 LR 组。LR 组 CAR 阳性 T 细胞的 PD-1 和 TIGIT 表达降低。多数患者（97.5%）出现 3 级不良事件，最常见为中性粒细胞减少（93.7%），其次为血小板减少（41.8%）和贫血（30.4%）。细胞因子释放综合征和神经系统事件分别发生于 57.0% 和 13.9% 的患者。3 级 CRS 发生率为 8.9%，未报告 4 级事件；3 级神经系统事件发生率为 3.8%。严重感染发生率为 25.3%，3 例患者发生 5 级感染。本试验已在 ClinicalTrials.gov 注册（NCT04836507）。
Anbalcabtagene autoleucel (Anbal-cel) is a CD19-directed CAR T-cell therapy incorporating dual PD-1 and TIGIT knockdown to enhance antitumor function and durability. We report the results of a Phase 1/2 study in patients with relapsed or refractory large B-cell lymphoma (LBCL). In Phase 2, 79 patients received Anbal-cel, and efficacy was evaluated in 73 patients. The complete response (CR) and partial response (PR) rates were 67.1% and 8.2%, respectively. Median progression-free survival (PFS) was 6.04 months (95% CI, 4.34-16.46), and the 6-, 12-, and 18-month PFS rates were 50.9%, 41.1%, and 35.2%, respectively. Median overall survival (OS) was not reached, with 12- and 18-month OS rates of 66.6% and 57.3%. CAR T-cell expansion was significantly greater in responders than in non-responders (median Cmax: 20,403 vs. 8,580 copies/ g). Patients were categorized into long-term response (LR) group or non-LR group based on sustained CR at 6 months. Reduced PD-1 and TIGIT expression on CAR-positive T cells was observed in LR group. Most patients (97.5%) experienced grade 3 adverse events, most commonly neutropenia (93.7%), followed by thrombocytopenia (41.8%) and anemia (30.4%). Cytokine release syndrome and neurologic events occurred in 57.0% and 13.9% of patients, respectively. Grade 3 CRS occurred in 8.9% of patients, with no grade 4 events reported, and grade 3 neurologic events occurred in 3.8%. Serious infections occurred in 25.3% of patients, and grade 5 infection was reported in 3 patients. This trial was registered at Clinicaltrials.gov (NCT04836507).
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