BMT Unit, Tel Aviv Medical Center, 6 Weizman St., Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Ann Hematol. 2019 Aug;98(8):1927-1932. doi: 10.1007/s00277-019-03719-6. Epub 2019 Jun 11.
Patients with acute myeloid leukemia (AML) who progress after exposure to hypomethylating agents (HMA) have a dismal prognosis. We hypothesized that the addition of venetoclax, a BCL-2 inhibitor, to AML patients who previously failed HMA might overcome resistance. Adult patients (≥ 18 years) with AML were eligible if leukemia relapsed after, or was refractory to HMA. In general, in addition to venetoclax, patients continued HMA or other low-intensity therapies. Patients who previously underwent allogeneic hematopoietic cell transplantation (HCT) were also eligible. Data were analyzed in November 2018. Twenty-three patients were treated between October 2016 and October 2018 and were eligible for this study. Median age was 76 years and 6 patients had leukemia that relapsed post allogeneic HCT. None of the patients experienced tumor lysis syndrome and toxicities were as expected and manageable. Febrile neutropenia was the most common toxicity (78% of patients). Median hospitalization time was 13 days. Forty-three percent of the patients achieved CR/CRi. Overall survival (OS) was 74% at 6 months and median OS in patients who achieved remission was 10.8 months. Higher number of blasts in both bone marrow and peripheral blood was associated with lower chances of CR, while higher WBC, LDH, and bone marrow or peripheral blasts were associated with increased mortality rate. The addition of venetoclax to patients with HMA-refractory AML may result in a substantial anti-leukemic activity, specifically in those achieving complete remission. This should be further tested in a well-designed prospective trial.
接受低甲基化剂 (HMA) 治疗后进展的急性髓系白血病 (AML) 患者预后不良。我们假设在先前接受 HMA 治疗失败的 AML 患者中添加 BCL-2 抑制剂维奈托克可能会克服耐药性。如果白血病在 HMA 后复发或对 HMA 耐药，则符合条件的成年患者（≥18 岁）患有 AML。一般来说，除维奈托克外，患者还继续接受 HMA 或其他低强度治疗。先前接受过异基因造血细胞移植 (HCT) 的患者也符合条件。数据于 2018 年 11 月进行分析。2016 年 10 月至 2018 年 10 月期间治疗了 23 例患者，并符合本研究条件。中位年龄为 76 岁，6 例患者的白血病在异基因 HCT 后复发。没有患者发生肿瘤溶解综合征，毒性与预期相符且可管理。发热性中性粒细胞减少症是最常见的毒性（78%的患者）。中位住院时间为 13 天。43%的患者达到 CR/CRi。6 个月时总生存率（OS）为 74%，达到缓解的患者中位 OS 为 10.8 个月。骨髓和外周血中 blast 数量越多，CR 机会越低，而白细胞计数（WBC）、乳酸脱氢酶（LDH）、骨髓或外周 blast 越高，死亡率越高。在 HMA 耐药性 AML 患者中添加维奈托克可能会产生显著的抗白血病活性，特别是在完全缓解的患者中。这应在精心设计的前瞻性试验中进一步测试。
