Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study
Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study
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DOI：
10.1016/s1470-2045(11)70386-2
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发表时间：
2012-04-01
期刊：
影响因子：
51.1
通讯作者：
O'Brien, Susan
中科院分区：
文献类型：
--
作者：
Kantarjian, Hagop;Thomas, Deborah;O'Brien, Susan
背景
难治性和复发性急性淋巴细胞白血病（ALL）患者的预后不佳。CD22在ALL患者中高度表达。奥英妥珠单抗是一种与卡奇霉素毒素偶联的CD22单克隆抗体。我们进行了一项2期研究以评估该抗体的疗效。
方法
我们于2010年6月至2011年3月在美国得克萨斯州休斯敦的MD安德森癌症中心招募患者。难治性和复发性ALL的成人和儿童符合入选条件。在开始招募儿童之前，先对10名成人进行了治疗。患者每3 - 4周静脉输注1.8 mg/m²奥英妥珠单抗，持续1小时（最初的3名成人和3名儿童在第一个疗程接受1.3 mg/m²）。主要终点是总体缓解（完全缓解或骨髓完全缓解但血小板计数未恢复，或中性粒细胞和血小板计数不完全恢复）。采用意向性治疗进行分析。本研究已注册，注册号为NCT01134575。
结果
49名患者入选并接受了治疗。中位年龄为36岁（范围6 - 80岁）。所有患者中超过50%的原始细胞表达CD22。疗程中位数为2个（范围1 - 5个），疗程之间的中位时间为3周（范围3 - 6周）。9名（18%）患者达到完全缓解，19名（39%）达到骨髓完全缓解，19名（39%）出现耐药疾病，2名（4%）在开始治疗的4周内死亡。总体缓解率为57%（95%置信区间42 - 71）。在第一个治疗疗程中最常见的不良事件是发热（20名患者为1 - 2级，9名患者为3 - 4级）、低血压（12名患者为1 - 2级，1名患者为3级）以及肝脏相关毒性作用（胆红素：12名患者为1 - 2级，2名患者为3级；转氨酶浓度升高：27名患者为1 - 2级，1名患者为3级）。
解释
奥英妥珠单抗作为难治性和复发性ALL的一种治疗方法显示出前景。
Background The outlook for patients with refractory and relapsed acute lymphocytic leukaemia (ALL) is poor. CD22 is highly expressed in patients with ALL. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the toxin calecheamicin. We did a phase 2 study to assess the efficacy of this antibody.Methods We recruited patients at the MD Anderson Cancer Center, Houston, TX, USA, between June, 2010, and March, 2011. Adults and children with refractory and relapsed ALL were eligible. Ten adults were treated before enrolment of children started. Patients were given 1 . 8 mg/m(2) inotuzumab ozogamicin intravenously over 1 h every 3-4 weeks (the first three adults and three children received 1 . 3 mg/m(2) in the first course). The primary endpoint was overall response (complete response or marrow complete response with no recovery of platelet count or incomplete recovery of neutrophil and platelet counts). Analysis was done by intention to treat. This study is registered, number NCT01134575.Findings 49 patients were enrolled and treated. Median age was 36 years (range 6-80). CD22 was expressed in more than 50% of blasts in all patients. The median number of courses was two (range one to five) and the median time between courses was 3 weeks (range 3-6). Nine (18%) patients had complete response, 19 (39%) had marrow complete response, 19 (39%) had resistant disease, and two (4%) died within 4 weeks of starting treatment. The overall response rate was 57% (95% CI 42-71). The most frequent adverse events during course one of treatment were fever (grade 1-2 in 20 patients, grade 3-4 in nine), hypotension (grade 1-2 in 12 patients, grade 3 in one), and liver-related toxic effects (bilirubin: grade 1-2 in 12 patients, grade 3 in two; raised aminotransferase concentration: grade 1-2 in 27 patients, grade 3 in one).Interpretation Inotuzumab ozogamicin shows promise as a treatment for refractory and relapsed ALL.