Division of Hematology, Stanford Cancer Institute, Stanford, CA.
Department of Pathology, University of New Mexico, Albuquerque, NM; and.
Blood Adv. 2019 Aug 13;3(15):2264-2271. doi: 10.1182/bloodadvances.2019000152.
There is an unmet need for effective therapies for advanced systemic mastocytosis (advSM). CD30 is expressed on the surface of neoplastic mast cells (MC) in more than 50% of patients with advSM. Brentuximab vedotin (BV) is a CD30-directed antibody-drug conjugate with preclinical evidence supporting both an antineoplastic effect and an attenuation of immunoglobulin E-associated mediator release. These observations are the basis for this phase 2 trial of BV monotherapy (1.8 mg/kg IV every 3 weeks up to 8 cycles) in patients with CD30-positive advSM. The primary objective was to determine the efficacy of BV according to International Working Group-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on Mastocytosis (IWG-MRT-ECNM) response criteria. Secondary objectives included evaluation of safety, changes in bone marrow (BM) MC burden, serum tryptase level, flow cytometric quantification of MC surface expression of CD30, and self-reported symptom burden. The trial enrolled 10 patients with a diagnosis of CD30 advSM (aggressive SM, SM with an associated hematologic neoplasm [SM-AHN], or mast cell leukemia [MCL]) with 1 or more signs of SM-related organ damage. According to IWG-MRT-ECNM criteria, none of the patients demonstrated better than stable disease with BV. In addition, there were no significant reductions in BM MC burden, serum tryptase levels, or MC surface expression of CD30. Self-reported symptom scores showed no durable improvement with BV treatment. We conclude that BV is not active as a single agent in CD30 advSM. This trial was registered at www.clinicaltrials.gov as #NCT01807598.
晚期系统性肥大细胞增多症（advSM）的有效治疗方法仍存在未满足的需求。在超过 50%的 advSM 患者中，CD30 表达于肿瘤性肥大细胞（MC）的表面。 Brentuximab vedotin（BV）是一种靶向 CD30 的抗体药物偶联物，具有支持抗肿瘤作用和减轻免疫球蛋白 E 相关介质释放的临床前证据。这些观察结果是该试验的基础，该试验评估了 BV 单药治疗（1.8 mg/kg IV，每 3 周一次，最多 8 个周期）在 CD30 阳性 advSM 患者中的疗效。主要目的是根据国际工作组-骨髓增殖性肿瘤研究和治疗-欧洲肥大细胞网络（IWG-MRT-ECNM）反应标准确定 BV 的疗效。次要目的包括评估安全性、骨髓（BM）MC 负担、血清类胰蛋白酶水平、MC 表面 CD30 表达的流式细胞术定量以及自我报告的症状负担的变化。该试验纳入了 10 名诊断为 CD30 advSM（侵袭性 SM、伴有血液系统肿瘤的 SM [SM-AHN]或肥大细胞白血病 [MCL]）且有 1 种或多种 SM 相关器官损伤迹象的患者。根据 IWG-MRT-ECNM 标准，BV 治疗后没有患者的疾病表现优于稳定疾病。此外，BM MC 负担、血清类胰蛋白酶水平或 MC 表面 CD30 表达均无显著降低。自我报告的症状评分显示 BV 治疗后无持久改善。我们得出结论，BV 作为单一药物在 CD30 advSM 中不具有活性。该试验在 www.clinicaltrials.gov 上注册，编号为 #NCT01807598。
