Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
Division of Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts.
Cancer. 2020 Mar 15;126(6):1264-1273. doi: 10.1002/cncr.32657. Epub 2019 Dec 20.
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.
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.
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.
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).
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.
复发/难治性急性髓系白血病（R/R AML）患者的预后仍然较差。专门针对 AML 的新型疗法受到高度关注。 Brentuximab vedotin（BV）是一种针对人类 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）再诱导化疗治疗 CD30 表达的 R/R AML 患者的安全性。
使用标准剂量递增设计，作者评估了 3 个 BV 剂量水平（0.9mg/kg、1.2mg/kg 和 1.8mg/kg），第 1 天单次给药，随后第 3 天至第 7 天给予 MEC。
未观察到剂量限制毒性，未达到最大耐受剂量。当与 MEC 联合使用时，BV 的推荐 2 期剂量确定为 1.8mg/kg。副作用谱与单独使用 MEC 化疗相似，最常见的 3 级及以上毒性为发热性中性粒细胞减少症、血小板减少症和贫血（毒性使用国家癌症研究所不良事件通用术语标准[第 4.0 版]进行分级）。在接受试验的 22 名患者中，复合缓解率为 36%，接受最高剂量 BV 治疗的患者复合缓解率为 42%。中位总生存期为 9.5 个月，缓解者中位无疾病生存期为 6.8 个月。约 55%的患者能够进行同种异体造血干细胞移植或供者淋巴细胞输注。
BV 联合 MEC 在 CD30 表达的 R/R AML 患者中被发现是安全的，值得进一步研究比较该联合方案与该人群中单独使用 MEC 的疗效（ClinicalTrials.gov 标识符 NCT01830777）。
复发/难治性急性髓系白血病（R/R AML）患者的预后极差。新的治疗组合正在积极研究中，以改善预后。作者研究了 brentuximab vedotin（一种识别称为 CD30 的标记物的抗体产品）与米托蒽醌、依托泊苷和阿糖胞苷（MEC，一种常见的化疗方案）联合用于表达 CD30 标记物的 R/R AML 患者的安全性。作者发现该联合方案是安全且耐受良好的。未来比较这种新联合方案与单独使用 MEC 的研究可以帮助确定该方案对该患者人群的疗效。
