2014年12月9日讯 /生物谷BIOON/ --2014年第56届美国血液学会年会（ASH）于12月6日-9日在美国旧金山举行。近日，艾伯维（AbbVie）在会上公布了实验性抗癌药venetoclax（ABT-199/GDC-0199）急性髓性白血病（ALL）II期临床项目的首批数据。在32例复发/难治急性髓性白血病（AML）患者中开展的一项研究，评估了venetoclax的初步疗效以及用作不适合强化治疗的ALL患者的一线治疗。研究结果表明，venetoclax治疗组总缓解率为15.5%，其中一例患者实现完全缓解（CR），另外4例实现完全缓解（CR）但血细胞计数未完全恢复（CRi）。
完全缓解（CR）指药物治疗后癌症所有体征消失。血细胞计数未完全恢复（CRi）的完全缓解（CR）指药物治疗后患者实现完全缓解的大多数标准。急性髓性白血病（AML）是一种恶性致命性血液癌症，是临床常见的白血病类型，生存率较低，该领域对新的有效治疗方案存在高度未获满足的医疗需求。
这是艾伯维首次公布venetoclax急性髓性白血病（ALL）II项目的数据。艾伯维表示，该研究的结果令人鼓舞。venetoclax是一种实验性B细胞淋巴瘤因子-2(BCL-2)抑制剂，目前正评估用于多种类型癌症的治疗。BCL-2可阻止一些细胞（包括淋巴细胞）的凋亡，该因子在发生于淋巴结、批准和免疫系统其他器官中的癌细胞高度表达。venetoclax旨在选择性抑制BCL-2因子的功能，恢复细胞的通讯系统，让癌细胞自我毁灭。
venetoclax由艾伯维与罗氏旗下基因泰克（Genentech）合作开发，双方正在开展一项III期研究，评估venetoclax治疗慢性淋巴细胞白血病（CLL）及其他一些癌症。
英文原文：AbbVie Presents Results from Phase 2 Study of Investigational Compound Venetoclax (ABT-199/GDC-0199) in Acute Myelogenous Leukemia at the 56th American Society of Hematology Annual Meeting
- AbbVie Presents for the First Time Results from the Venetoclax Phase 2 Program in Acute Myelogenous Leukemia
- Study Evaluated Preliminary Efficacy of Venetoclax in 32 Patients with Relapsed/Refractory Acute Myelogenous Leukemia and as Frontline Therapy in Patients Unfit for Intensive Treatment
NORTH CHICAGO, Ill., Dec. 7, 2014 /PRNewswire/ -- AbbVie (NYSE: ABBV) presented during an oral presentation at the American Society of Hematology's 56th Annual Meeting new results from a Phase 2 study of investigational compound venetoclax (ABT-199/GDC-0199) in patients with acute myelogenous leukemia (AML). AML is an aggressive and deadly type of blood cancer, in which the body produces too many of a specific type of white blood cell (myeloblast), which can crowd out healthy blood cells. In the study, the venetoclax group showed an overall response rate (ORR) of 15.5 percent, with one patient achieving a complete response and four patients achieving a complete response with incomplete blood count recovery.
A complete response (CR) is sometimes called complete remission, and refers to the disappearance of all signs of cancer in response to cancer treatment. A complete response with incomplete blood count recovery (CRi) is when a patient fulfills most – but not all – criteria to be classified as a complete response. CRi indicates activity but is not the same as a complete response.
"Acute myelogenous leukemia is an aggressive cancer with low survival rates, and there is a high need among patients and healthcare providers for new, effective treatment options," said Marina Konopleva, M.D., Ph.D., associate professor of the Department of Leukemia, Division of Cancer Medicine, at the University of Texas MD Anderson Cancer Center. "The results of this trial of venetoclax are encouraging and warrant additional study in patients with AML."
"This is the first time we have reported results from the venetoclax Phase 2 clinical trial in AML. We believe venetoclax's potential in this indication warrants further investigation," said Gary Gordon, M.D., Ph.D., vice president, oncology clinical development, AbbVie. "The results from this study and AbbVie's other abstracts presented during ASH represent the continued progress of our strong blood cancer development program and demonstrate our commitment to discovering innovative treatment options."
About the Study
The Phase 2, open-label, multicenter clinical trial was designed to evaluate the preliminary efficacy of venetoclax in 32 patients with relapsed/refractory AML or as frontline therapy for patients who are unfit for intensive therapy. Secondary objectives included safety and pharmacodynamics assessments.
Isocitrate dehydrogenase (IDH) mutations are genetic mutations found in a small number of patients with AML and may influence outcomes. IDH mutations were found in three patients who achieved CR/CRi. Two of these patients also achieved minimal residual disease (MRD) negativity, which represents a response to a given therapy and describes the detection of zero leukemic cells during treatment or after a patient is in remission.
Additionally, researchers assessed patients' bone marrow myeloblast (blast, or immature white blood cells) counts. A bone marrow blast count of greater than 20 percent is generally required for a diagnosis of AML and reduction of blasts indicate a diminished presence of leukemia. The median bone marrow blast count in evaluable patients treated with venetoclax decreased 36 percent. Of note, six patients (19%) had at least a 50 percent bone marrow blast reduction.
Common adverse events (≥25% of patients) included nausea, diarrhea, fatigue, neutropenia and vomiting. Grade 3 and 4 adverse events (in ≥3 patients) included febrile neutropenia, anemia and pneumonia.
These data indicate that further study of venetoclax in AML patients is warranted. Venetoclax will be studied in combination with other medicines sometimes used in treating patients with AML. Development and evaluation of the compound in several blood cancers is ongoing.
About Venetoclax (ABT-199/GDC-0199)
Venetoclax is an investigational inhibitor of the B-cell lymphoma-2 (BCL-2) protein being evaluated for the treatment of patients with various cancer types. The BCL-2 protein prevents apoptosis of some cells, including lymphocytes, and can be highly expressed in cancers in the lymph nodes, spleen and other organs of the immune system. Venetoclax is designed to selectively inhibit the function of the BCL-2 protein, leading to restoration of the communication system that tells cancer cells to self-destruct. Venetoclax is being developed in collaboration with Genentech in the United States and Roche outside the United States. Together, the companies are pioneering BCL-2 research with venetoclax, which is currently being evaluated in a Phase 3 clinical trial for the treatment of CLL and several other cancers. Venetoclax is an investigational compound and its safety and efficacy have not been evaluated by the FDA or any other health authority.
About Acute Myelogenous Leukemia (AML)
Acute myelogenous leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow and is one of the most common types of leukemia among adults. In AML, the body produces too many of a specific type of white blood cell (myeloblast), which can crowd out healthy blood cells.1 Approximately 19,000 new cases of AML were diagnosed in 2014 in the U.S. and more than 10,000 deaths were attributed to the disease in 2014.7