地西他滨联合维奈克拉治疗 TP53 突变急性髓系白血病的疗效。
Outcomes of TP53-mutant acute myeloid leukemia with decitabine and venetoclax.
机构信息
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
出版信息
Cancer. 2021 Oct 15;127(20):3772-3781. doi: 10.1002/cncr.33689. Epub 2021 Jul 13.
BACKGROUND
TP53 mutation (TP53 ) confers an adverse prognosis in acute myeloid leukemia (AML). Venetoclax with hypomethylating agents is a current standard for older patients; however, recent reports suggest that TP53 confers resistance to venetoclax. The authors investigated the outcomes of patients with TP53 AML who were treated with a 10-day decitabine and venetoclax (DEC10-VEN) (ClinicalTrials.gov identifier NCT03404193).
METHODS
Patients with newly diagnosed AML received decitabine 20 mg/m for 10 days every 4 to 6 weeks for induction, followed by decitabine for 5 days after response. The venetoclax dose was 400 mg daily. TP53 was identified in bone marrow samples using next-generation sequencing, with sensitivity of 5%. Outcomes were analyzed according to European LeukemiaNet 2017 guidelines.
RESULTS
Among 118 patients (median age, 72 years; age range, 49-89 years), 63 (53%) had secondary AML, 39 (33%) had AML with complex karyotype, and 35 (30%) had TP53 AML. The median TP53 variant allele frequency was 32% (interquartile range, 16%-65%), 8 patients (23%) had only a single TP53 mutation, 15 (43%) had multiple mutations, and 12 (34%) had mutation and deletion. Outcomes were significantly worse in patients who had TP53 AML compared with those who had wild-type TP53 AML, with an overall response rate of 66% vs 89% (P = .002), a complete response/complete response with incomplete hematologic recovery rate of 57% vs 77% (P = .029), and a 60-day mortality of 26% vs 4% (P < .001), respectively. Patients with TP53 versus wild-type TP53 had shorter overall survival at 5.2 versus 19.4 months, respectively (hazard ratio, 4.67; 95% CI, 2.44-8.93; P < .0001), and shorter relapse-free survival at 3.4 versus 18.9 months (hazard ratio, 4.80; 95% CI, 1.97-11.69; P < .0001), respectively. Outcomes with DEC10-VEN in patients with TP53 AML were comparable to historical results with 10-day decitabine alone.
CONCLUSIONS
Patients with TP53 AML have lower response rates and shorter survival with DEC10-VEN.
背景
TP53 突变（TP53 ）在急性髓系白血病（AML）中预后不良。维奈托克联合低甲基化剂是老年患者的当前标准治疗方法；然而，最近的报告表明 TP53 对维奈托克产生耐药性。作者研究了接受 10 天阿扎胞苷和维奈托克（DEC10-VEN）治疗的 TP53 AML 患者的结局（ClinicalTrials.gov 标识符 NCT03404193）。
方法
新诊断为 AML 的患者每 4 至 6 周接受阿扎胞苷 20 mg/m 治疗 10 天作为诱导治疗，随后在有缓解时接受 5 天阿扎胞苷治疗。维奈托克的剂量为每天 400 mg。使用下一代测序技术在骨髓样本中检测 TP53，灵敏度为 5%。根据欧洲白血病网 2017 年指南分析结局。
结果
在 118 例患者中（中位年龄为 72 岁；年龄范围为 49-89 岁），63 例（53%）为继发性 AML，39 例（33%）为伴有复杂核型的 AML，35 例（30%）为 TP53 AML。TP53 变异等位基因频率的中位数为 32%（四分位距，16%-65%），8 例（23%）仅有单个 TP53 突变，15 例（43%）有多个突变，12 例（34%）有突变和缺失。与野生型 TP53 AML 患者相比，TP53 AML 患者的结局明显较差，总体缓解率分别为 66%和 89%（P =.002），完全缓解/完全缓解伴不完全血液学恢复率分别为 57%和 77%（P =.029），60 天死亡率分别为 26%和 4%（P <.001）。TP53 患者与野生型 TP53 患者的总生存期分别为 5.2 个月和 19.4 个月（风险比，4.67；95%CI，2.44-8.93；P <.0001），无复发生存期分别为 3.4 个月和 18.9 个月（风险比，4.80；95%CI，1.97-11.69；P <.0001）。TP53 AML 患者接受 DEC10-VEN 治疗的结局与单独使用 10 天阿扎胞苷的历史结果相当。
结论
TP53 AML 患者接受 DEC10-VEN 治疗的缓解率较低，生存时间较短。
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