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Drugs. 2017 Sep;77(14):1603-1610. doi: 10.1007/s40265-017-0802-5.
Intravenous inotuzumab ozogamicin (Besponsa; Pfizer) is an anti-CD22 monoclonal antibody-calicheamicin conjugate that binds to CD22-expressing tumour cells. Upon binding, the complex is internalised and the cytotoxic calicheamicin derivative is released inside the cell, inducing double-strand DNA breakage and subsequent cell death. In June 2017, the EMA granted inotuzumab ozogamicin approval as monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia (ALL). The use of inotuzumab ozogamicin in adult patients with Philadelphia chromosome-positive, relapsed or refractory CD22-positive B-cell precursor ALL is restricted to those who have failed treatment with at least one tyrosine kinase inhibitor. Inotuzumab ozogamicin was granted priority review for the treatment of relapsed or refractory B-cell precursor ALL by the US FDA in February 2017. In the USA, a phase III trial evaluating inotuzumab ozogamicin in combination with frontline chemotherapy in adults with newly diagnosed B-cell ALL has recently been initiated and inotuzumab ozogamicin is under phase II evaluation in childhood CD22-positive B-cell ALL. Inotuzumab ozogamicin combination therapies are also being evaluated in the phase I/II or II setting in ALL and chronic myeloid leukaemia and in the phase I setting in Burkitt's lymphoma. This article summarises the milestones in the development of inotuzumab ozogamicin leading to this first approval for ALL.
静脉注射伊妥珠单抗奥佐米星（Besponsa；辉瑞）是一种抗 CD22 单克隆抗体-加利车霉素偶联物，可与表达 CD22 的肿瘤细胞结合。结合后，该复合物被内化，细胞毒性加利车霉素衍生物在细胞内释放，诱导双链 DNA 断裂和随后的细胞死亡。2017 年 6 月，EMA 批准伊妥珠单抗奥佐米星作为单药治疗复发或难治性 CD22 阳性 B 细胞前体急性淋巴细胞白血病（ALL）的成人患者。伊妥珠单抗奥佐米星在费城染色体阳性、复发或难治性 CD22 阳性 B 细胞前体 ALL 的成年患者中的使用仅限于那些至少接受过一种酪氨酸激酶抑制剂治疗失败的患者。伊妥珠单抗奥佐米星因治疗复发或难治性 B 细胞前体 ALL 而于 2017 年 2 月获得美国 FDA 的优先审查。在美国，最近启动了一项评估伊妥珠单抗奥佐米星联合一线化疗治疗新诊断为 B 细胞 ALL 的成人患者的 III 期试验，并且伊妥珠单抗奥佐米星正在儿童 CD22 阳性 B 细胞 ALL 中进行 II 期评估。伊妥珠单抗奥佐米星联合疗法也正在 ALL 和慢性髓性白血病的 I/II 期或 II 期评估中，在 Burkitt 淋巴瘤中也在 I 期评估中。本文总结了导致此次 ALL 首次批准的伊妥珠单抗奥佐米星的发展里程碑。
