Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA.
Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
Leuk Lymphoma. 2024 Sep;65(9):1281-1291. doi: 10.1080/10428194.2024.2346755. Epub 2024 May 7.
AMG 330, a bispecific T-cell engager (BiTE®) that binds CD33 and CD3 on T cells facilitates T-cell-mediated cytotoxicity against CD33+ cells. This first-in-human, open-label, dose-escalation study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AMG 330 in adults with relapsed/refractory acute myeloid leukemia (R/R AML). Amongst 77 patients treated with AMG 330 (0.5 µg/day-1.6 mg/day) on 14-day or 28-day cycles, maximum tolerated dose was not reached; median duration of treatment was 29 days. The most frequent treatment-related adverse events were cytokine release syndrome (CRS; 78%) and rash (30%); 10% of patients experienced grade 3/4 CRS. CRS was mitigated with stepwise dosing of AMG 330, prophylactic dexamethasone, and early treatment with tocilizumab. Among 60 evaluable patients, eight achieved complete remission or morphologic leukemia-free state; of the 52 non-responders, 37% had ≥50% reduction in AML bone marrow blasts. AMG 330 is a promising CD33-targeted therapeutic strategy for R/R AML.
AMG 330 是一种双特异性 T 细胞衔接器（BiTE®），能结合 T 细胞上的 CD33 和 CD3，促进 T 细胞对 CD33+细胞的细胞毒性。这项首次在人体中进行的、开放性标签的、剂量递增研究评估了 AMG 330 在复发/难治性急性髓系白血病（R/R AML）成人患者中的安全性、药代动力学、药效学和初步疗效。在接受 AMG 330 治疗的 77 例患者中（0.5μg/天-1.6mg/天，14 天或 28 天周期），未达到最大耐受剂量；中位治疗持续时间为 29 天。最常见的治疗相关不良事件是细胞因子释放综合征（CRS；78%）和皮疹（30%）；10%的患者发生 3/4 级 CRS。通过逐步给药 AMG 330、预防性地塞米松和早期使用托珠单抗来缓解 CRS。在 60 例可评估患者中，8 例达到完全缓解或形态学无白血病状态；52 例无应答者中，37%的患者 AML 骨髓原始细胞减少≥50%。AMG 330 是一种有前途的针对 R/R AML 的 CD33 靶向治疗策略。
