Results of a phase I trial with Haploidentical mbIL-21 ex vivo expanded NK cells for patients with multiply relapsed and refractory AML,American Journal of Hematology

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Results of a phase I trial with Haploidentical mbIL-21 ex vivo expanded NK cells for patients with multiply relapsed and refractory AML
American Journal of Hematology ( IF 10.1 ) Pub Date : 2024-03-05 , DOI: 10.1002/ajh.27281
Stefan O Ciurea ₁ , Piyanuch Kongtim ₁ , Samer Srour ₂ , Julianne Chen ₂ , Doris Soebbing ₂ , Elizabeth Shpall ₂ , Katayoun Rezvani ₂ , Robin Nakkula ₃ , Aarohi Thakkar ₃ , Ella C Troy ₃ , Alex A Cash ₃ , Gregory Behbehani ₃ , Kai Cao ₄ , Jolie Schafer ₅ , Richard E Champlin ₂ , Dean A Lee _{3,

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Affiliation

Natural killer (NK)-cells have potent anti-tumor effects, yet it remains unclear if they are effective for patients with relapsed acute myeloid leukemia (AML). In a phase I clinical trial, we treated 12 patients (median age 60 years) with refractory AML (median 5 lines of prior therapy, median bone marrow blast count of 47%) with fludarabine/cytarabine followed by 6 infusions of NK-cells expanded from haploidentical donors using K562 feeder cells expressing membrane-bound IL21 and 4-1BBL. Patients received 10⁶–10⁷/kg/dose. No toxicity or graft-versus-host disease (GVHD) was observed and MTD was not reached. Seven patients (58.3%) responded and achieved a complete remission (CR) with/without count recovery. Median time to best response was 48 days. Five responding patients proceeded to a haploidentical transplant from the same donor. After a median follow-up of 52 months, 1-year overall survival (OS) for the entire group was 41.7%, better for patients who responded with CR/CRi (57.14%), and for patients who responded and underwent transplantation (60%). Persistence and expansion of donor-derived NK-cells were identified in patients' blood, and serum IFNγ levels rose concurrently with NK cell infusions. A higher count-functional inhibitory KIR was associated with higher likelihood of achieving CR/CRi. In conclusion, we observed a significant response to ex vivo expanded NK-cell administration in refractory AML patients without adverse effects.

中文翻译：

使用单倍体 mbIL-21 离体扩增 NK 细胞治疗多发复发难治性 AML 患者的 I 期试验结果

自然杀伤 (NK) 细胞具有有效的抗肿瘤作用，但尚不清楚它们是否对复发性急性髓性白血病 (AML) 患者有效。在一项 I 期临床试验中，我们用氟达拉滨/阿糖胞苷治疗了 12 名难治性 AML 患者（中位年龄 60 岁）（中位先前治疗 5 行，中位骨髓母细胞计数为 47%），随后注射 6 次扩大的 NK 细胞来自使用表达膜结合 IL21 和 4-1BBL 的 K562 饲养细胞的半相合供体。患者接受 10 ⁶ –10 ⁷ /kg/剂量。未观察到毒性或移植物抗宿主病 (GVHD)，且未达到 MTD。七名患者 (58.3%) 有反应并达到完全缓解 (CR)，有/没有计数恢复。最佳反应的中位时间为 48 天。五名有反应的患者接受了来自同一捐献者的单倍体移植。中位随访 52 个月后，整个组的 1 年总生存率 (OS) 为 41.7%，其中对 CR/CRi 有反应的患者 (57.14%) 以及有反应并接受移植的患者 (60 %）。在患者血液中发现了供体来源的 NK 细胞的持续存在和扩增，血清 IFNγ 水平随着 NK 细胞输注而上升。较高的计数功能抑制 KIR 与实现 CR/CRi 的可能性较高相关。总之，我们观察到难治性 AML 患者对离体扩增 NK 细胞给药有显着反应，且没有不良反应。

更新日期：2024-03-05

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