Kim Won Seog, Shortt Jake, Zinzani Pier Luigi, Mikhailova Natalia, Radeski Dejan, Ribrag Vincent, Domingo Domenech Eva, Sawas Ahmed, Alexis Karenza, Emig Michael, Elbadri Riham, Hajela Pallavi, Ravenstijn Paulien, Pinto Sheena, Garcia Linta, Overesch Andre, Pietzko Kerstin, Horwitz Steven
Department of Hematology-Oncology, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Medicine, School of Clinical Sciences, Faculty of Medicine, Nursing & Health Sciences, Monash University, Clayton, Victoria, Australia.
Clin Cancer Res. 2025 Jan 6;31(1):65-73. doi: 10.1158/1078-0432.CCR-24-1913.
Patients with relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) generally have poor prognoses and limited treatment options. This study evaluated the efficacy of a novel CD30/CD16A bispecific innate cell engager, acimtamig (AFM13), in patients with R/R PTCL.
Patients included those with CD30 expression in ≥1% of tumor cells and who were R/R following ≥1 prior line of systemic therapy. Acimtamig (200 mg) was administered once weekly in 8-week cycles. The primary endpoint was the overall response rate by fluorodeoxyglucose-PET per independent review committee; secondary and exploratory endpoints included duration of response, safety, progression-free survival, and overall survival.
The overall response rate in 108 patients was 32.4% [95% confidence interval (CI), 23.7, 42.1] with a complete response rate of 10.2% (95% CI, 5.2, 17.5); the median duration of response was 2.3 months (95% CI, 1.9, 6.5). Patients with R/R angioimmunoblastic T-cell lymphoma exhibited the greatest number of responses [53.3% (95% CI, 34.3, 71.7)]. Responses were independent of CD30 expression level, prior brentuximab vedotin treatment, or steroid premedication. Acimtamig exhibited a tolerable safety profile; the most common treatment-related adverse events were infusion-related reactions in 27 patients (25.0%) and neutropenia in 11 patients (10.2%). No cases of cytokine release syndrome or acimtamig-related deaths were reported. Despite exhibiting promising clinical activity and tolerable safety in a heavily pretreated PTCL population, the study did not meet the criteria for the primary endpoint.
The promising clinical efficacy observed warrants further investigation, and development of acimtamig for patients with R/R CD30+ lymphomas continues in combination with allogeneic NK cells.
复发或难治性（R/R）外周T细胞淋巴瘤（PTCL）患者的预后通常较差，治疗选择有限。本研究评估了一种新型CD30/CD16A双特异性天然细胞衔接器阿西他米（AFM13）在R/R PTCL患者中的疗效。
患者包括肿瘤细胞中CD30表达≥1%且在≥1线全身治疗后复发或难治的患者。阿西他米（200mg）每周给药一次，疗程为8周。主要终点是由独立审查委员会评估的氟脱氧葡萄糖-PET总体缓解率；次要终点和探索性终点包括缓解持续时间、安全性、无进展生存期和总生存期。
108例患者的总体缓解率为32.4%[95%置信区间（CI），23.7，42.1]，完全缓解率为10.2%（95%CI，5.2，17.5）；中位缓解持续时间为2.3个月（95%CI，1.9，6.5）。R/R血管免疫母细胞性T细胞淋巴瘤患者的缓解例数最多[53.3%（95%CI，34.3，71.7）]。缓解与CD30表达水平、既往接受过的本妥昔单抗治疗或类固醇预处理无关。阿西他米表现出可耐受的安全性；最常见的治疗相关不良事件为27例患者（25.0%）出现的输液相关反应和11例患者（10.2%）出现的中性粒细胞减少。未报告细胞因子释放综合征或与阿西他米相关的死亡病例。尽管在经过大量预处理的PTCL患者群体中表现出有前景的临床活性和可耐受的安全性，但该研究未达到主要终点标准。
观察到的有前景的临床疗效值得进一步研究，阿西他米与同种异体NK细胞联合用于R/R CD30+淋巴瘤患者的研发仍在继续。
