Inotuzumab ozogamicin（InO）是一种抗体药物偶联物，由一个人源化的单克隆抗体与细胞表面受体CD22耦合，通过酸不稳定连接物与细胞毒性calicheamicin药物负载结合而成。在成人和儿童试验中，InO在复发和难治性B细胞前体急性淋巴细胞性白血病（BCP-ALL）的单药和联合化疗方案中显示出显著的活性。同时，在新诊断的老年患者中也已得到应用，而针对新诊断的儿童患者和身体健康的成年患者的临床试验正在进行中。值得注意的毒副作用包括窦样梗阻综合征（SOS），特别是在InO后进行造血干细胞移植（HSCT）的患者中，以及造血抑制和B细胞无形成，这会增加感染风险，特别是与细胞毒性化疗联合使用时。在复发/难治（R/R）情况下，当使用InO时，必须考虑计划的后续治疗方式以减轻HSCT的SOS风险，并考虑转入嵌合抗原受体CAR-T治疗时的潜在B细胞无形成。目前正在进行研究探索InO失败或耐药的机制，但已涉及到调节或丢失CD22表达、替代CD22剪接和高Bcl-2表达。在本综述中，我们将总结InO目前可用的数据，重点是儿童试验，以及探讨包括组合疗法在内的未来发展方向。 版权所有© 2023 Rubinstein 和 O’Brien。

Inotuzumab ozogamicin (InO) is an antibody drug conjugate composed of a humanized monoclonal antibody targeting the cell surface receptor CD22 coupled to a cytotoxic calicheamicin payload via an acid labile linker. InO has shown significant activity in relapsed and refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in both single agent and combination chemotherapy regimens in adult and pediatric trials. Its use in newly diagnosed elderly patients has also been established while clinical trials investigating its use in newly diagnosed pediatric patients and fit adults are ongoing. Notable toxicities include sinusoidal obstruction syndrome (SOS), particularly in patients who undergo hematopoietic stem cell transplantation (HSCT) after InO as well as myelosuppression and B-cell aplasia which confer increased infection risk, particularly in combination with cytotoxic chemotherapy. In the relapsed/refractory (R/R) setting, the planned subsequent curative therapy modality must be considered when using InO to mitigate SOS risk if proceeding to HSCT and account for potential B-cell aplasia if proceeding to chimeric antigen receptor CAR-T therapy. Studies exploring mechanisms of resistance or failure of InO are ongoing but modulation or loss CD22 expression, alternative CD22 splicing, and high Bcl-2 expression have been implicated. In this review, we will summarize the currently available data on InO, with an emphasis on pediatric trials, and explore future directions including combinatorial therapy.Copyright © 2023 Rubinstein and O’Brien.