Safety and efficacy of navitoclax, a BCL-2 and BCL-X(L) inhibitor, in patients with relapsed or refractory lymphoid malignancies: results from a phase 2a study.
Safety and efficacy of navitoclax, a BCL-2 and BCL-X(L) inhibitor, in patients with relapsed or refractory lymphoid malignancies: results from a phase 2a study.
复制标题
NAVITOCLAX，BCL-2和BCL-X（L）抑制剂的安全性和功效，对患有复发或难治性淋巴恶性肿瘤的患者：2A期研究的结果。
DOI：
10.1080/10428194.2020.1845332
复制
发表时间：
2021-04
影响因子：
2.6
通讯作者：
中科院分区：
文献类型：
--
作者：
Navitoclax是一种新型BCL-2和BCL-XL抑制剂，在淋巴肿瘤I/IIa期研究（NCT 00406809）的剂量递增部分显示出有前景的抗肿瘤活性。在此，我们报告了IIa期部分的持续安全性和疗效结果。入组了26例复发性/难治性滤泡性淋巴瘤（n = 11，A组）和其他复发性/难治性淋巴恶性肿瘤（n = 15，B组）成人患者。Navitoclax给药方案包括150 mg 7天导入剂量，随后250 mg每日给药，如果250 mg剂量耐受，可选择在14天后进一步增加至325 mg。所有患者均发生至少1起治疗相关不良事件（TRAE）。17例（65.4%）患者报告了3/4级TRAE;血小板减少症（38.5%）和中性粒细胞减少症（30.8%）是最常见的。2例患者报告了严重AE;无致死性AE（研究药物末次给药后30天内未发生死亡）。客观缓解率（完全和部分）为23.1%（6/26; A组：9.1%，B组：33.3%）。中位无进展生存期和至进展时间相同：4.9个月（95% CI：3.0，8.2）;中位总生存期：24.8个月（无法计算95% CI）。Navitoclax单药治疗在少数复发性/难治性淋巴系统恶性肿瘤患者中具有可接受的安全性特征和有意义的临床活性。
Navitoclax, a novel BCL-2 and BCL-XL 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 (n = 11, Arm A) and other relapsed/refractory lymphoid malignancies (n = 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.
登录
查看更多内容
影响因子：
64.5
作者：
Mason, Kylie D.;Carpinelli, Marina R.;Kile, Benjamin T.
通讯作者：
Kile, Benjamin T.
影响因子：
50.3
作者：
Certo, Michael;Moore, Victoria Del Gaizo;Letai, Anthony
通讯作者：
Letai, Anthony
影响因子：
50.5
作者：
de Vos, S.;Swinnen, L. J.;Flowers, C. R.
通讯作者：
Flowers, C. R.
影响因子：
3.5
作者：
Marschitz, I;Tinhofer, I;Greil, R
通讯作者：
Greil, R
影响因子：
20.3
作者：
Cheson, BD;Bennett, JM;Rai, KR
通讯作者：
Rai, KR