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依妥珠单抗奥滨尤妥珠单抗治疗成人急性淋巴细胞白血病:研发历程、现状与未来方向

Inotuzumab ozogamicin in adult acute lymphoblastic leukemia: Development, current status, and future directions.

机构信息

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Hématologie Clinique, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.

出版信息

Cancer. 2024 Nov 1;130(21):3631-3646. doi: 10.1002/cncr.35505. Epub 2024 Aug 2.

Abstract

Inotuzumab ozogamicin (InO) is an antibody-drug conjugate approved for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (ALL). Several clinical trials are investigating InO in combination with low-intensity chemotherapy or other anti-ALL-targeted therapies in the salvage and frontline settings, notably in older adults who often cannot tolerate intensive chemotherapy and tend to have higher-risk disease. InO is also increasingly used to bridge patients to hematopoietic stem cell transplantation (HSCT), in sequence with chimeric antigen receptor T-cell therapy, to eliminate measurable residual disease and to prevent post-HSCT relapse. Veno-occlusive disease/sinusoidal obstruction syndrome is a potential complication of InO treatment, particularly when followed by HSCT. Herein, the authors review the historical development and current status of InO, strategies for mitigating the risk of InO-related veno-occlusive disease/sinusoidal obstruction syndrome, and future directions for InO research and clinical use.

摘要

依妥珠单抗奥滨尤妥珠单抗(InO)是一种抗体药物偶联物,已获批用于治疗复发/难治性 B 细胞急性淋巴细胞白血病(ALL)。多项临床试验正在探索 InO 联合低强度化疗或其他针对 ALL 的靶向疗法在挽救和一线治疗中的应用,特别是在不能耐受强化化疗且疾病往往具有更高风险的老年患者中。InO 也越来越多地用于桥接患者进行造血干细胞移植(HSCT),与嵌合抗原受体 T 细胞疗法序贯使用,以消除可测量的残留疾病并预防 HSCT 后复发。静脉闭塞病/窦状隙阻塞综合征是 InO 治疗的潜在并发症,尤其是在紧随 HSCT 之后。本文作者回顾了 InO 的历史发展和现状、减轻 InO 相关静脉闭塞病/窦状隙阻塞综合征风险的策略,以及 InO 研究和临床应用的未来方向。

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