Objective: To observe the treatment response of a two-dose regimen of inotuzumab ozogamicin (inotuzumab), a monoclonal antibody targeting CD22, for patients with heavily treated relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), including those failed or relapsed after chimeric antigen receptor (CAR) -T-cell therapy. Methods: Pediatric and adult patients who received two doses of inotuzumab and who were evaluated after inotuzumab treatment were included. Antibody infusions were performed between March 2020 and September 2022. All patients expressed CD22 antigen as detected by flow cytometry (>80% leukemic cells displaying CD22) before treatment. For adults, the maximum dosage per administration was 1 mg (with a total of two administrations). For children, the maximum dosage per administration was 0.85 mg/m(2) (no more than 1 mg/dose; total of two administrations). The total dosage administered to each patient was less than the standard dosage of 1.8 mg/m(2). Results: Twenty-one patients with R/R B-ALL were included, including five children (<18 years old) and sixteen adults. Seventeen patients presented with 5.0% -99.0% leukemic blasts in the bone marrow/peripheral blood or with extramedullary disease, and four patients were minimal residual disease (MRD) -positive. Fourteen patients underwent both CD19 and CD22 CAR-T-cell therapy, four underwent CD19 CAR-T-cell therapy, and three underwent blinatumomab therapy. Eleven patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). After inotuzumab treatment, 14 of 21 patients (66.7% ) achieved a complete response (CR, one was MRD-positive CR), and all four MRD-positive patients turned MRD-negative. Four of six patients who failed recent CD22 CAR-T-cell therapy achieved a CR after subsequent inotuzumab treatment. Seven patients (33.3% ) demonstrated no response. Grade 1-3 hepatotoxicity occurred in five patients (23.8% ), one child with no response experienced hepatic veno-occlusive disease (HVOD) during salvage transplantation and recovered completely. Conclusion: For patients with heavily treated R/R B-ALL, including those who had undergone allo-HSCT and CD19/CD22 CAR-T-cell therapy, the two-dose regimen of inotuzumab resulted in a CR rate of 66.7%, and the frequency of hepatotoxicity and HVOD was low.
目的： 观察靶向CD22的抗体奥加伊妥珠单抗两剂疗法对于多线治疗后特别是嵌合抗原受体T细胞（CAR-T细胞）治疗后复发/难治急性B淋巴细胞白血病（R/R B-ALL）的疗效。 方法： 回顾性分析了2020年3月至2022年9月在北京高博博仁医院血液科接受两剂CD22单抗治疗并评估了疗效的R/R B-ALL患者（包括成人和儿童）。所有患者治疗前均经流式细胞术检测证实表达CD22抗原（>80%白血病细胞表达CD22）。所用CD22单抗为注射用奥加伊妥珠单抗，剂型为1 mg/瓶。成人每剂1 mg，儿童每剂不超过1 mg，最大剂量0.85 mg/m(2)；每例患者用两剂，总剂量均小于标准剂量1.8 mg/m(2)。 结果： 共纳入21例R/R B-ALL患者，5例儿童（<18岁）和16例成人。17例患者骨髓/外周血白血病细胞比例为5.0%~99.0%或伴有髓外病变，4例仅骨髓微小残留病（MRD）阳性。14例患者接受过CD19和CD22 CAR-T细胞治疗，4例接受过CD19 CAR-T细胞治疗，3例接受过CD3/CD19双特异性抗体治疗。11例为异基因造血干细胞移植后患者。经CD22单抗治疗后，14例（66.7%）患者获得完全缓解（CR，其中1例为MRD阳性CR），4例仅有骨髓MRD阳性者均转为MRD阴性。6例CD22 CAR-T细胞治疗失败者中，4例经随后的CD22单抗治疗达到CR。7例（33.3%）患者治疗无效。5例（23.8%）患者在抗体治疗过程中发生Ⅰ~Ⅲ级肝毒性，1例无效患儿在挽救性移植过程中发生肝静脉闭塞病（HVOD），经治疗后痊愈。 结论： 对于多线治疗（包括移植及CD19/CD22 CAR-T细胞）后的R/R B-ALL患者，两剂CD22抗体方案疗效好、费用低，肝毒性和HVOD发生率低。.
Keywords: CD22; Inotuzumab ozogamicin; Leukemia, B-cell, acute; Relapsed/refractory.