Gemtuzumab Ozogamicin in NPM1-Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study
Gemtuzumab Ozogamicin in NPM1-Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study
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DOI：
10.1200/jco.19.01406
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发表时间：
2020-02-20
影响因子：
45.3
通讯作者：
Doehner, Hartmut
中科院分区：
文献类型：
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作者：
Schlenk, Richard F.;Paschka, Peter;Doehner, Hartmut
目的在NPM1突变的急性髓系白血病(AML)中CD33的高表达为评价吉珠单抗(GO)在该AML实体中的应用提供了理论基础。我们进行了一项随机试验，以评估GO与强化诱导和巩固治疗联合治疗NPM1突变的AML。患者和方法2010年5月至2017年9月，符合强化治疗条件的18岁患者被随机分配到预先接受伊达比星、阿糖胞苷、依托泊苷和全反式维甲酸诱导治疗，并加或不加GO。在患者招募完成6个月后评估早期(P=0.02)无事件生存(EFS)的主要终点。结果588例患者随机分为两组，标准组296例，围术组292例。GO组与标准组的EFS差异无统计学意义(危险比0.83；95%可信区间0.65~1.04；P=0.10)。诱导治疗早期死亡率GO组为10.3%，标准组为5.7%(P=0.05)。双臂的死亡原因主要是感染。完全缓解(CR)或完全缓解(CR)且血液学不完全恢复(CRI)的患者，GO组与标准组相比，累积复发率(CIR)显著降低(P=0.005)，累积死亡率无差异(P=0.80)。亚组分析显示，GO对女性、年轻(？70岁)、Flt3内部串联复制阴性的患者在EFS和CIR方面具有显著的有益效果。结论该试验没有达到早期EFS的主要终点，主要是由于GO组早期死亡率较高。然而，在诱导治疗后达到CR/CRI的患者中，与标准ARM相比，GO中的复发显著减少。
PURPOSE High CD33 expression in acute myeloid leukemia (AML) with mutated NPM1 provides a rationale for the evaluation of gemtuzumab ozogamicin (GO) in this AML entity. We conducted a randomized trial to evaluate GO in combination with intensive induction and consolidation therapy in NPM1-mutated AML. PATIENTS AND METHODS Between May 2010 and September 2017, patients ? 18 years old and considered eligible for intensive therapy were randomly assigned up front for induction therapy with idarubicin, cytarabine, etoposide, and all-trans-retinoic acid with or without GO. The early (P = .02) primary end point of event-free survival (EFS) was evaluated 6 months after completion of patient recruitment. RESULTS Five hundred eighty-eight patients were randomly assigned (standard arm, n = 296; GO arm, n = 292). EFS in the GO arm was not significantly different compared with that in the standard arm (hazard ratio, 0.83; 95% CI, 0.65 to 1.04; P = .10). The early death rate during induction therapy was 10.3% in the GO arm and 5.7% in the standard arm (P = .05). Causes of death in both arms were mainly infections. The cumulative incidence of relapse (CIR) in patients achieving a complete remission (CR) or CR with incomplete hematologic recovery (CRi) was significantly reduced in the GO arm compared with the standard arm (P = .005), with no difference in the cumulative incidence of death (P = .80). Subgroup analysis revealed a significant beneficial effect of GO in female, younger (? 70 years), and FLT3 internal tandem duplication?negative patients with respect to EFS and CIR. CONCLUSION The trial did not meet its early primary end point of EFS, mainly as a result of a higher early death rate in the GO arm. However, in patients achieving CR/CRi after induction therapy, significantly fewer relapses occurred in the GO compared with the standard arm.