Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancer. 2013 Aug 1;119(15):2728-36. doi: 10.1002/cncr.28136. Epub 2013 Apr 30.
CD22 expression occurs in >90% of patients with acute lymphocytic leukemia (ALL). Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, is active in ALL.
Patients with refractory-relapsed ALL received treatment with inotuzumab. The first 49 patients received single-dose, intravenous inotuzumab at doses of 1.3 to 1.8 mg/m2 every 3 to 4 weeks. In the next 41 patients, the schedule was modified to inotuzumab weekly at a dose of 0.8 mg/m2 on day 1 and at a dose of 0.5 mg/m2 on days 8 and 15, every 3 to 4 weeks, based on higher in vitro efficacy with more frequent exposure.
Ninety patients were treated; 68% were in salvage 2 or beyond. Overall, 17 patients (19%) achieved a complete response (CR), 27 (30%) had a CR with no platelet recovery (CRp), and 8 (9%) had a bone marrow CR (no recovery of counts), for an overall response rate of 58%. Response rates were similar for single-dose and weekly dose inotuzumab (57% vs 59%, respectively). The median survival was 6.2 months overall, 5.0 months with the single-dose schedule, and 7.3 months with the weekly dose schedule. The median survival was 9.2 months for patients in salvage 1 (37% at 1 year), 4.3 months for patients in salvage 2, and 6.6 months for patients in salvage 3 or later. The median remission duration was 7 months. Reversible bilirubin elevation, fever, and hypotension were observed less frequently on the weekly dose. In total, 36 of 90 patients (40%) underwent allogeneic stem cell transplantation. Veno-occlusive disease was noted in 6 of 36 patients after stem cell transplantation (17%), was less frequent after the weekly schedule (7%), and with less alkylators in the preparative regimen.
Inotuzumab single-agent therapy was highly active, safe, and convenient in patients with refractory-relapsed ALL. A weekly dose schedule appeared to be equally effective and less toxic than a single-dose schedule.
CD22 表达发生于 >90%的急性淋巴细胞白血病（ALL）患者中。Inotuzumab ozogamicin 是一种与加利车霉素结合的 CD22 单克隆抗体，在 ALL 中具有活性。
接受难治性/复发性 ALL 治疗的患者接受 Inotuzumab 治疗。前 49 例患者接受 1.3 至 1.8 mg/m2 的单剂量、静脉内 Inotuzumab，每 3 至 4 周一次。在接下来的 41 例患者中，根据更高的体外疗效和更频繁的暴露，将方案修改为每周一次 Inotuzumab，剂量为 0.8 mg/m2，第 1 天；剂量为 0.5 mg/m2，第 8 天和第 15 天，每 3 至 4 周一次。
90 例患者接受了治疗；68%处于挽救性 2 期或更晚期。总体而言，17 例（19%）患者达到完全缓解（CR），27 例（30%）患者达到无血小板恢复的 CR（CRp），8 例（9%）患者达到骨髓 CR（计数无恢复），总缓解率为 58%。单剂量和每周剂量 Inotuzumab 的缓解率相似（分别为 57%和 59%）。总体中位生存期为 6.2 个月，单剂量方案为 5.0 个月，每周剂量方案为 7.3 个月。挽救性 1 期患者的中位生存期为 9.2 个月（1 年时为 37%），挽救性 2 期患者为 4.3 个月，挽救性 3 期或更晚期患者为 6.6 个月。中位缓解持续时间为 7 个月。每周剂量组较少出现胆红素升高、发热和低血压。共有 90 例患者中的 36 例（40%）接受了异基因造血干细胞移植。在接受干细胞移植的 36 例患者中，有 6 例（17%）出现静脉闭塞性疾病，每周方案的发生率较低（7%），且预处理方案中烷化剂较少。
Inotuzumab 单药治疗在难治性/复发性 ALL 患者中具有高度活性、安全性和便利性。每周剂量方案与单剂量方案同样有效且毒性更小。
