Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia
Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia
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DOI：
10.1182/bloodadvances.2019000243
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发表时间：
2019-10-22
期刊：
影响因子：
7.5
通讯作者：
Pollyea, Daniel A.
中科院分区：
文献类型：
--
作者：
Winters, Amanda C.;Gutman, Jonathan A.;Pollyea, Daniel A.
维奈托克被批准用于老年未经治疗的急性髓性白血病（AML）患者。维奈托克在批准前可用于标签外使用。我们评估了单机构使用维奈托克/阿扎胞苷的标签外使用经验，并将结果与在同一机构使用该方案的临床试验队列进行了比较。回顾性分析了33例不适合或不愿意接受诱导化疗的未经治疗的AML患者，并将其与33例接受相同治疗的患者进行了比较。结果进行了比较，并进行了比较，以一个理论的情况下，试验外的患者接受诱导。数字微滴聚合酶链反应评价可测量残留病变（MRD）。试验结束后，几乎所有需要使用维奈托克的患者都可以使用。接受治疗的试验外患者的完全缓解（CR）/CR伴血细胞计数不完全恢复率为63.3%，试验患者为84.9%（P = 0.081）。接受治疗的试验外患者的中位总生存期为381天（95%置信区间[CI]，174，未达到），而试验患者为880天（95% CI，384，未达到）（P = 0.041）。既往暴露于低甲基化药物与不良结局相关。维奈托克/阿扎胞苷的缓解率并不劣于患者接受诱导的理论情况，并且诱导的早期死亡率低于预期。MRD阴性是可实现的。与在临床试验背景下接受治疗的患者相比，在“现实世界”情况下使用试验外维奈托克/阿扎胞苷治疗的新诊断急性髓细胞白血病患者的结局较差。此外，与诱导化疗相比，这种疗法可能同样有效，毒性更低。
Venetoclax is approved for older untreated acute myeloid leukemia (AML) patients. Venetoclax was available prior to approval off-label. We assessed our single-institution off-label experience with venetoclax/azacitidine, comparing outcomes with a clinical trial cohort that administered this regimen at the same institution. Thirty-three untreated AML patients unfit or unwilling to receive induction chemotherapy and prescribed venetoclax/ azacitidine off-trial were retrospectively analyzed and compared with 33 patients who received the same therapy on trial. Outcomes were compared, and comparisons were made to a theoretical scenario in which off-trial patients received induction. Digital droplet polymerase chain reaction evaluated measurable residual disease (MRD). Off-trial venetoclax was attainable in nearly all patients for whom this was desired. The complete remission (CR)/CR with incomplete blood count recovery rate was 63.3% for off-trial patients who received treatment and 84.9% for trial patients (P = .081). The median overall survival for off-trial patients who received treatment was 381 days (95% confidence interval [CI], 174, not reached) vs 880 days (95% CI, 384, not reached) for trial patients (P = .041). Prior exposure to hypomethylating agents was associated with worse outcomes. Response rates with venetoclax/azacitidine were not inferior to a theoretical scenario in which patients received induction, and early death rates were less than expected with induction. MRD negativity was achievable. Newly diagnosed AML patients treated in a "real-world" scenario with off-trial venetoclax/azacitidine had inferior outcomes compared with patients treated in the setting of a clinical trial. Additionally, this therapy may be as effective, and less toxic, when compared with induction chemotherapy.