Venetoclax showed promising activity in a small phase II trial in relapsed/refractory Waldenström macroglobulinemia (WM). To report the clinical activity of venetoclax and prognostic factors associated with outcomes in a larger cohort, we retrospectively identified 76 patients with relapsed/refractory lymphoplasmacytic lymphoma (LPL)/WM treated with venetoclax monotherapy at nine US medical centers. The median age at venetoclax treatment initiation was 66 years. MYD88, CXCR4, and TP53 mutations were detected in 65 (94%), 23 (40%), and 10 (22%) patients, respectively. The median number of prior lines of treatment was 3, including covalent BTK inhibitor in 82% and alkylating agent in 71% of patients. The overall and major response rates to venetoclax were 70% and 63%, respectively. The median and 2-year progression-free survival (PFS) were 28.5 months and 57%, respectively. The median and 2-year overall survival were not reached and 82%, respectively. Prior treatment with BTK inhibitor was the only factor associated with PFS in multivariate analysis (hazard ratio 2.97, p = 0.012). Venetoclax dose interruptions and/or reductions occurred in 27 patients (41%). Five patients (7%) developed laboratory tumor lysis syndrome (TLS), including 3 (4%) with clinical TLS. Venetoclax resulted in a high response rate and a prolonged PFS in patients with heavily pretreated LPL/WM.
一项针对复发/难治性华氏巨球蛋白血症的小型II期试验显示，Venetoclax具有良好疗效。为了在更大规模队列中报告Venetoclax的临床活性及其疗效相关预后因素，我们回顾性分析了来自美国九家医疗中心的76例接受Venetoclax单药治疗的复发/难治性淋巴浆细胞淋巴瘤/华氏巨球蛋白血症患者。开始Venetoclax治疗的中位年龄为66岁。分别有65例（94%）、23例（40%）和10例（22%）患者检测到MYD88、CXCR4和TP53突变。既往治疗中位线数为3线，其中82%的患者曾接受共价BTK抑制剂治疗，71%曾接受烷化剂治疗。Venetoclax的总体缓解率和主要缓解率分别为70%和63%。中位无进展生存期为28.5个月，2年无进展生存率为57%。中位总生存期未达到，2年总生存率为82%。多变量分析显示，既往BTK抑制剂治疗是唯一与无进展生存期相关的因素（风险比2.97，p=0.012）。27例患者（41%）需要中断和/或减少Venetoclax剂量。5例患者（7%）出现实验室肿瘤溶解综合征，其中3例（4%）为临床肿瘤溶解综合征。对于经过多线治疗的淋巴浆细胞淋巴瘤/华氏巨球蛋白血症患者，Venetoclax能实现高缓解率并延长无进展生存期。
肿瘤(癌症)患者之家