Farhad Ravandi, Marion Subklewe, Roland B Walter, Pankit Vachhani, Gert Ossenkoppele, Veit Buecklein, Hartmut Döhner, Mojca Jongen-Lavrencic, Claudia D Baldus, Lars Fransecky, Timothy S Pardee, Hagop Kantarjian, Priscilla K Yen, Lata Mukundan, Bharat Panwar, Marc R Yago, Suresh Agarwal, Sophia K Khaldoyanidi, Anthony Stein
{"title":"AMG 330 对复发/难治性急性髓细胞性白血病成人患者的安全性和耐受性:1a 期剂量递增研究。","authors":"Farhad Ravandi, Marion Subklewe, Roland B Walter, Pankit Vachhani, Gert Ossenkoppele, Veit Buecklein, Hartmut Döhner, Mojca Jongen-Lavrencic, Claudia D Baldus, Lars Fransecky, Timothy S Pardee, Hagop Kantarjian, Priscilla K Yen, Lata Mukundan, Bharat Panwar, Marc R Yago, Suresh Agarwal, Sophia K Khaldoyanidi, Anthony Stein","doi":"10.1080/10428194.2024.2346755","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Safety and tolerability of AMG 330 in adults with relapsed/refractory AML: a phase 1a dose-escalation study.\",\"authors\":\"Farhad Ravandi, Marion Subklewe, Roland B Walter, Pankit Vachhani, Gert Ossenkoppele, Veit Buecklein, Hartmut Döhner, Mojca Jongen-Lavrencic, Claudia D Baldus, Lars Fransecky, Timothy S Pardee, Hagop Kantarjian, Priscilla K Yen, Lata Mukundan, Bharat Panwar, Marc R Yago, Suresh Agarwal, Sophia K Khaldoyanidi, Anthony Stein\",\"doi\":\"10.1080/10428194.2024.2346755\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":18047,\"journal\":{\"name\":\"Leukemia & Lymphoma\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Leukemia & Lymphoma\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/10428194.2024.2346755\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Leukemia & Lymphoma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10428194.2024.2346755","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/7 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
AMG 330 是一种双特异性 T 细胞吸引剂 (BiTE®),能与 T 细胞上的 CD33 和 CD3 结合,促进 T 细胞介导的针对 CD33+ 细胞的细胞毒性。这项首例人体开放标签剂量递增研究评估了AMG 330在复发/难治性急性髓性白血病(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77名接受AMG 330(0.5微克/天-1.6毫克/天)治疗的患者中,治疗周期为14天或28天,均未达到最大耐受剂量;中位治疗时间为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%的患者出现3/4级CRS。通过逐步服用AMG 330、预防性地塞米松和早期使用托珠单抗治疗,CRS得到了缓解。在60名可评估的患者中,有8人获得了完全缓解或无形态白血病状态;在52名无应答者中,有37%的急性髓细胞性白血病骨髓细胞数减少了≥50%。AMG 330是治疗R/R急性髓细胞性白血病的一种前景看好的CD33靶向治疗策略。
Safety and tolerability of AMG 330 in adults with relapsed/refractory AML: a phase 1a dose-escalation study.
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.
期刊介绍:
Leukemia & Lymphoma in its fourth decade continues to provide an international forum for publication of high quality clinical, translational, and basic science research, and original observations relating to all aspects of hematological malignancies. The scope ranges from clinical and clinico-pathological investigations to fundamental research in disease biology, mechanisms of action of novel agents, development of combination chemotherapy, pharmacology and pharmacogenomics as well as ethics and epidemiology. Submissions of unique clinical observations or confirmatory studies are considered and published as Letters to the Editor