Department of Hematology, Toranomon Hospital, Minato-ku, Tokyo, Japan.
Department of Hematology and Oncology, University of Fukui Hospital, Fukui, Japan.
Jpn J Clin Oncol. 2021 May 28;51(6):857-864. doi: 10.1093/jjco/hyab018.
Venetoclax plus azacitidine is indicated in the USA for the treatment of newly diagnosed acute myeloid leukaemia in older patients (≥75 years) or those ineligible for induction chemotherapy due to co-morbidities.
In this phase 1/2 study (NCT02265731), Japanese patients (≥60 years) with untreated (ineligible for induction chemotherapy) or relapsed/refractory acute myeloid leukaemia received oral venetoclax 400 mg/day (3-day ramp up in cycle 1) plus subcutaneous or intravenous azacitidine 75 mg/m2 on days 1-7 per 28-day cycle until disease progression or unacceptable toxicity.
As of 10 December 2019, six patients were enrolled (median age: 75 years; untreated: n = 5; relapsed/refractory: n = 1); median treatment duration: 10.3 months (range, 0.7-29.4). Most common grade ≥ 3 adverse events were lymphopaenia and febrile neutropaenia (n = 4 each). Four patients reported serious adverse events; only an event of grade 3 fungal pneumonia was considered possibly related to both study drugs, requiring dose interruption of venetoclax and delay of azacitidine. Five (83%) patients had responses (complete remission: n = 3). Median time to first response of complete remission/complete remission with incomplete count recovery was 1.0 month (range, 0.8-5.5); median overall survival: 15.7 months (95% confidence interval: 6.2, not reached).
Venetoclax plus azacitidine was well tolerated and showed high response rates in Japanese patients with acute myeloid leukaemia.
维奈托克联合阿扎胞苷在美国被批准用于治疗新诊断的老年（≥75 岁）或因合并症不适合诱导化疗的急性髓系白血病患者。
在这项 1/2 期研究（NCT02265731）中，未经治疗（不适合诱导化疗）或复发/难治性急性髓系白血病的日本患者（≥60 岁）接受口服维奈托克 400mg/天（第 1 周期 3 天爬坡），联合每 28 天周期皮下或静脉给予阿扎胞苷 75mg/m2，第 1-7 天，直至疾病进展或无法耐受毒性。
截至 2019 年 12 月 10 日，共入组 6 例患者（中位年龄：75 岁；未经治疗：n=5；复发/难治性：n=1）；中位治疗时间：10.3 个月（范围，0.7-29.4）。最常见的≥3 级不良事件为淋巴细胞减少和发热性中性粒细胞减少（各有 4 例）。4 例患者报告发生严重不良事件；仅 1 例 3 级真菌感染性肺炎被认为可能与两种研究药物相关，需要中断维奈托克和延迟阿扎胞苷的剂量。5 例（83%）患者有缓解（完全缓解：n=3）。完全缓解/不完全计数恢复的完全缓解首次反应的中位时间为 1.0 个月（范围，0.8-5.5）；中位总生存期：15.7 个月（95%置信区间：6.2，未达到）。
维奈托克联合阿扎胞苷在日本急性髓系白血病患者中耐受性良好，且具有较高的缓解率。
