de Vos Sven, Leonard John P, Friedberg Jonathan W, Zain Jasmine, Dunleavy Kieron, Humerickhouse Rod, Hayslip John, Pesko John, Wilson Wyndham H
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Weill Cornell Medicine and New York-Presbyterian Hospital, New York, NY, USA.
Leuk Lymphoma. 2021 Apr;62(4):810-818. doi: 10.1080/10428194.2020.1845332. Epub 2020 Nov 25.
Navitoclax, a novel BCL-2 and BCL-X inhibitor, demonstrated promising antitumor activity in the dose-escalation part of a phase 1/2a study (NCT00406809) in lymphoid tumors. Herein, we report the continued safety and efficacy results of the phase 2a portion. Twenty-six adult patients with relapsed/refractory follicular lymphoma ( = 11, Arm A) and other relapsed/refractory lymphoid malignancies ( = 15, Arm B) were enrolled. Navitoclax administration schedule consisted of a 150-mg 7-day lead-in dose followed by 250-mg daily dosing with the option to further increase to 325 mg after 14 days if the 250-mg dose was tolerated. All patients experienced at least 1 treatment-related adverse event (TRAE). Seventeen (65.4%) patients reported grade 3/4 TRAEs; thrombocytopenia (38.5%) and neutropenia (30.8%) were the most common. Two patients reported serious AEs; none were fatal (no deaths occurred within 30 days of last dose of study drug). The objective response rate (complete and partial) was 23.1% (6/26; Arm A: 9.1%, Arm B: 33.3%). Median progression-free survival and time to progression were identical: 4.9 months (95% CI: 3.0, 8.2); median overall survival: 24.8 months (95% CI could not be computed). Navitoclax monotherapy has an acceptable safety profile and meaningful clinical activity in a minority of patients with relapsed/refractory lymphoid malignancies.
纳维托克司（Navitoclax）是一种新型的BCL-2和BCL-X抑制剂，在一项1/2a期淋巴瘤研究（NCT00406809）的剂量递增阶段显示出有前景的抗肿瘤活性。在此，我们报告2a期部分的持续安全性和疗效结果。纳入了26例复发/难治性滤泡性淋巴瘤成年患者（A组11例）和其他复发/难治性淋巴系统恶性肿瘤患者（B组15例）。纳维托克司给药方案包括150 mg的7天导入剂量，随后每日250 mg给药，如果250 mg剂量耐受，14天后可进一步增加至325 mg。所有患者均经历至少1次治疗相关不良事件（TRAE）。17例（65.4%）患者报告3/4级TRAE；血小板减少（38.5%）和中性粒细胞减少（30.8%）最为常见。2例患者报告严重不良事件；均非致命（末次给药研究药物后30天内无死亡）。客观缓解率（完全缓解和部分缓解）为23.1%（26例中的第6例；A组：9.1%，B组：33.3%）。无进展生存期和疾病进展时间中位数相同：4.9个月（95%CI：3.0，8.2）；总生存期中位数：24.8个月（95%CI无法计算）。纳维托克司单药治疗在少数复发/难治性淋巴系统恶性肿瘤患者中具有可接受的安全性和有意义的临床活性。
