BACKGROUND Outcomes for patients with relapsed/refractory acute myeloid leukemia (R/R AML) remain poor. Novel therapies specifically targeting AML are of high interest. Brentuximab vedotin (BV) is an antibody-drug conjugate that is specific for human CD30. In this phase 1 dose escalation study, the authors evaluated the safety of BV combined with mitoxantrone, etoposide, and cytarabine (MEC) re-induction chemotherapy for patients with CD30-expressing R/R AML. METHODS Using a standard dose escalation design, the authors evaluated 3 dose levels of BV (0.9 mg/kg, 1.2 mg/kg, and 1.8 mg/kg) administered once on day 1 followed by MEC on days 3 through 7. RESULTS There were no dose-limiting toxicities noted and the maximum tolerated dose was not reached. The recommended phase 2 dose of BV was determined to be 1.8 mg/kg when combined with MEC. The side effect profile was similar to that expected from MEC chemotherapy alone, with the most common grade ≥3 toxicities being febrile neutropenia, thrombocytopenia, and anemia (toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). Among the 22 patients enrolled on the trial, the composite response rate was 36%, with a composite response rate of 42% noted among those who received the highest dose of BV. The median overall survival was 9.5 months, with a median disease-free survival of 6.8 months observed among responders. Approximately 55% of patients were able to proceed with either allogeneic hematopoietic stem cell transplantation or donor lymphocyte infusion. CONCLUSIONS The combination of BV with MEC was found to be safe in patients with CD30-expressing R/R AML and warrants further study comparing this combination with the use of MEC alone in this population (ClinicalTrials.gov identifier NCT01830777). LAY SUMMARY The outcomes for patients with relapsed/refractory acute myeloid leukemia (R/R AML) are exceptionally poor. New and emerging treatment combinations are actively being studied in an effort to improve outcomes. The authors examined the combination of brentuximab vedotin, an antibody product that recognizes a marker called CD30, with mitoxantrone, etoposide, and cytarabine (MEC), a common chemotherapy regimen, in patients with R/R AML that expressed the CD30 marker. The authors found that the combination was safe and well tolerated. Future studies comparing this new combination with the use of MEC alone can help to inform its effectiveness for this patient population.

中文翻译：

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在CD30表达复发/难治性急性髓细胞性白血病患者中，药物-药物结合物brentuximab vedotin联合诱导化疗的1期研究。

背景技术对于复发/难治性急性髓细胞性白血病（R / R AML）患者的治疗效果仍然较差。特别针对AML的新型疗法引起了人们的极大兴趣。Brentuximab vedotin（BV）是一种针对人CD30的抗体-药物偶联物。在这项1期剂量递增研究中，作者评估了BV联合米托蒽醌，依托泊苷和阿糖胞苷（MEC）再诱导化疗对表达CD30的R / R AML患者的安全性。方法使用标准剂量递增设计，作者评估了在第1天一次施用3种BV剂量水平（0.9 mg / kg，1.2 mg / kg和1.8 mg / kg），然后在第3至7天进行了MEC。没有发现剂量限制性毒性，并且未达到最大耐受剂量。当与MEC结合使用时，建议的BV 2期推荐剂量为1.8 mg / kg。副作用与仅通过MEC化疗所预期的相似，最常见的≥3级毒性是高热性中性粒细胞减少，血小板减少和贫血（毒性是根据美国国家癌症研究所不良事件通用术语标准[4.0版]分级的） 。在参与该试验的22名患者中，复合反应率为36％，其中BV最高剂量的复合反应率为42％。中位总体生存期为9.5个月，响应者中无疾病生存期的中位数为6.8个月。大约55％的患者能够进行同种异体造血干细胞移植或供体淋巴细胞输注。结论发现BV与MEC的结合在表达CD30的R / R AML患者中是安全的，因此有必要进行进一步研究，以比较该人群与单独使用MEC的结合（ClinicalTrials.gov标识符NCT01830777）。发明内容复发性/难治性急性髓细胞性白血病（R / R AML）患者的预后极差。为了改善治疗效果，正在积极研究新出现的治疗组合。作者检查了可识别CD30标记的抗体产品brentuximab vedotin与米托蒽醌，依托泊苷和阿糖胞苷（MEC）（一种常见的化疗方案）在表达CD30标记的R / R AML患者中的组合。作者发现这种组合是安全的并且耐受性良好。