Background: Patients with relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) generally have poor prognoses and limited treatment options. Materials & Methods: 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 overall response rate (ORR) by fluorodeoxyglucose-positron emission tomography per independent review committee; secondary and exploratory endpoints included duration of response (DoR), safety, progression-free survival, and overall survival. Results: The ORR in 108 patients was 32.4% (95% CI: 23.7, 42.1) with a complete response rate of 10.2% (95% CI: 5.2, 17.5); median DoR 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. Conclusions: The promising clinical efficacy observed warrants further investigation, and development of acimtamig for patients with R/R CD30+ lymphomas continues in combination with allogeneic natural killer cells.

中文翻译：

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acimtamig （AFM13） 在 CD30 阳性、复发或难治性外周 T 细胞淋巴瘤患者中的 2 期研究


背景：复发或难治性 （R/R） 外周 T 细胞淋巴瘤 （PTCL） 患者通常预后不良，治疗选择有限。材料和方法：这项研究评估了新型CD30/CD16A双特异性先天细胞参与剂acimtamig（AFM13，对R/R PTCL患者的疗效。患者包括在 ≥1% 的肿瘤细胞中表达 CD30 的患者，以及在既往 ≥1 线全身治疗后出现 R/R 的患者。Acimtamig （200 mg） 每周给药一次，周期为 8 周。主要终点是独立审查委员会通过氟脱氧葡萄糖-正电子发射断层扫描的总体缓解率 （ORR）;次要和探索终点包括缓解持续时间 （DoR） 、安全性、无进展生存期和总生存期。结果： 108 例患者的 ORR 为 32.4% （95% CI： 23.7， 42.1），完全缓解率为 10.2% （95% CI： 5.2， 17.5）;中位 DoR 为 2.3 个月 （95% CI： 1.9， 6.5）。R/R 血管免疫母细胞性 T 细胞淋巴瘤患者表现出最多的反应 （53.3% [95% CI： 34.3， 71.7]）。反应与 CD30 表达水平、既往 brentuximab vedotin 治疗或类固醇术前用药无关。Acimtamig 表现出可耐受的安全性;最常见的治疗相关不良事件是 27 例患者 （25.0%） 的输液相关反应和 11 例患者 （10.2%） 的中性粒细胞减少。未报告细胞因子释放综合征或 acimtamig 相关死亡病例。尽管在经过大量预处理的 PTCL 人群中表现出有希望的临床活性和可耐受的安全性，但该研究并未达到主要终点的标准。 结论： 观察到的有希望的临床疗效值得进一步研究，并且继续开发 acimtamig治疗 R/R CD30 + 淋巴瘤患者与同种异体自然杀伤细胞联合治疗。