Olin Jacqueline L, Griffiths Carrie L, Smith Morgan B
1 Levine College of Health Sciences, Wingate University School of Pharmacy, Wingate, NC, USA.
2 Hematology/Oncology, Novant Health Presbyterian Medical Center, Charlotte, NC, USA.
J Oncol Pharm Pract. 2018 Oct;24(7):517-524. doi: 10.1177/1078155217718383. Epub 2017 Jul 11.
Patients with chronic lymphocytic leukemia with the 17p deletion have a poor prognosis and treatment options are limited. Venetoclax, a novel B-cell lymphoma-2 inhibitor, has been approved for treatment-experienced chronic lymphocytic leukemia patients with the 17p deletion. A phase 1 dose-escalation study to 400 mg daily showed overall response rates across all doses of 79% with a complete response achieved in 20%. A phase 2 multicenter open-label study demonstrated overall response rate of 79.4% of patients (95% confidence interval 70.5-86.6) with median duration of follow-up of 12.1 months (IQR 10.1-14.2). Tumor lysis syndrome has been observed during initiation and titration. Assessing risk of tumor lysis syndrome prior to therapy initiation is essential to provide appropriate prophylactic medications. Neutropenia, potentially warranting dose reduction or discontinuation, has been observed. Venetoclax has demonstrated activity in other leukemias, multiple myeloma, and lymphomas. Venetoclax has shown response, and is well tolerated in patients with highly resistant chronic lymphocytic leukemia. It has the potential to be part of the treatment armamentarium for other malignancies.
伴有17p缺失的慢性淋巴细胞白血病患者预后较差，治疗选择有限。维奈克拉是一种新型的B细胞淋巴瘤-2抑制剂，已被批准用于治疗有治疗史的伴有17p缺失的慢性淋巴细胞白血病患者。一项每日剂量递增至400mg的1期研究显示，所有剂量的总体缓解率为79%，完全缓解率为20%。一项2期多中心开放标签研究表明，患者的总体缓解率为79.4%（95%置信区间70.5-86.6），中位随访时间为12.1个月（四分位间距10.1-14.2）。在开始治疗和滴定过程中观察到肿瘤溶解综合征。在开始治疗前评估肿瘤溶解综合征的风险对于提供适当的预防药物至关重要。已观察到中性粒细胞减少，可能需要降低剂量或停药。维奈克拉在其他白血病、多发性骨髓瘤和淋巴瘤中已显示出活性。维奈克拉已显示出疗效，并且在高度耐药的慢性淋巴细胞白血病患者中耐受性良好。它有可能成为其他恶性肿瘤治疗手段的一部分。
