Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study
Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study
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DOI：
10.1200/jco.18.01600
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发表时间：
2019-05-20
影响因子：
45.3
通讯作者：
Roboz, Gail J.
中科院分区：
文献类型：
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作者：
Wei, Andrew H.;Strickland, Stephen A., Jr.;Roboz, Gail J.
急性髓细胞白血病（AML）患者不能耐受强化化疗，有效的治疗选择有限。一项国际Ib/II期研究评价了维奈托克，一种选择性B细胞白血病/淋巴瘤-2抑制剂，与低剂量阿糖胞苷（LDAC）一起治疗老年AML患者的安全性和初步疗效。允许既往接受过骨髓增生异常综合征治疗，包括低甲基化药物（HMA）。82例患者接受推荐的II期剂量治疗：维奈托克600 mg/天口服，28天为一周期，LDAC（20 mg/m2/天）皮下注射，第1 - 10天。关键终点为耐受性、安全性、缓解率、缓解持续时间（DOR）和总生存期（OS）。结果中位年龄为74岁（范围：63 ~ 90岁），49%有继发性AML，29%有HMA治疗史，32%有低风险细胞遗传学特征。常见的3级或以上不良事件为发热性中性粒细胞减少（42%）、血小板减少（38%）和WBC计数降低（34%）。早期（30天）死亡率为6%。54%的患者达到完全缓解（CR）/CR，但血细胞计数恢复不完全（首次缓解的中位时间为1.4个月）。中位OS为10.1个月（95% CI，5.7 - 14.2），中位DOR为8.1个月（95% CI，5.3 - 14.9个月）。在既往无HMA暴露的患者中，62%的患者达到CR/CR伴血细胞计数不完全恢复，中位DOR为14.8个月（95% CI，5.5个月至未达到），中位OS为13.5个月结论维奈托克加LDAC具有可管理的安全性特征，在不适合强化化疗的老年AML患者中产生快速和持久的缓解。高缓解率和低早期死亡率加上快速和持久的缓解使venetoclax和LDAC成为不适合强化化疗的老年人的一种有吸引力的新型治疗方法。(C)2019年美国临床肿瘤学会
PURPOSE Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. An international phase Ib/II study evaluated the safety and preliminary efficacy of venetoclax, a selective B-cell leukemia/lymphoma-2 inhibitor, together with low-dose cytarabine (LDAC) in older adults with AML.PATIENTS AND METHODS Adults 60 years or older with previously untreated AML ineligible for intensive chemotherapy were enrolled. Prior treatment of myelodysplastic syndrome, including hypomethylating agents (HMA), was permitted. Eighty-two patients were treated at the recommended phase II dose: venetoclax 600 mg per day orally in 28-day cycles, with LDAC (20 mg/m(2) per day) administered subcutaneously on days 1 to 10. Key end points were tolerability, safety, response rates, duration of response (DOR), and overall survival (OS).RESULTS Median age was 74 years (range, 63 to 90 years), 49% had secondary AML, 29% had prior HMA treatment, and 32% had poor-risk cytogenetic features. Common grade 3 or greater adverse events were febrile neutropenia (42%), thrombocytopenia (38%), and WBC count decreased (34%). Early (30-day) mortality was 6%. Fifty-four percent achieved complete remission (CR)/CR with incomplete blood count recovery (median time to first response, 1.4 months). The median OS was 10.1 months (95% CI, 5.7 to 14.2), and median DOR was 8.1 months (95% CI, 5.3 to 14.9 months). Among patients without prior HMA exposure, CR/CR with incomplete blood count recovery was achieved in 62%, median DOR was 14.8 months (95% CI, 5.5 months to not reached), and median OS was 13.5 months (95% CI, 7.0 to 18.4 months).CONCLUSION Venetoclax plus LDAC has a manageable safety profile, producing rapid and durable remissions in older adults with AML ineligible for intensive chemotherapy. High remission rate and low early mortality combined with rapid and durable remission make venetoclax and LDAC an attractive and novel treatment for older adults not suitable for intensive chemotherapy. (C) 2019 by American Society of Clinical Oncology