Bouligny Ian M, Murray Graeme, Doyel Michael, Patel Tilak, Boron Josh, Tran Valerie, Gor Juhi, Hang Yiwei, Alnimer Yanal, Zacholski Kyle, Venn Chad, Wages Nolan A, Grant Steven, Maher Keri R
Division of Hematology and Oncology Department of Internal Medicine Virginia Commonwealth University Massey Cancer Center Richmond Virginia USA.
Virginia Commonwealth University School of Medicine Richmond Virginia USA.
EJHaem. 2023 Feb 24;4(2):381-392. doi: 10.1002/jha2.663. eCollection 2023 May.
Treatment paradigms for acute myeloid leukemia (AML) have evolved at a rapid pace in recent years. The combination of venetoclax with a hypomethylating agent prolonged survival in clinical trials when compared to hypomethylating agent monotherapy. However, little is known about the performance of venetoclax-based regimens outside of clinical trials, given conflicting safety and efficacy data. Even less is known about the impact of the hypomethylating agent backbone. In this study, we demonstrate that decitabine-venetoclax is associated with a significantly higher rate of grade three or higher thrombocytopenia, but lower rates of lymphocytopenia compared to azacitidine-venetoclax. There was no difference in response or survival across ELN 2017 cytogenetic risk categories in the overall cohort. Significantly more patients succumb to relapsed or refractory disease than death from any other cause. We demonstrated that a Charlson comorbidity index score threshold of seven identifies exceptionally high-risk patients, providing evidence for clinical use to reduce the risk of early treatment-related mortality. Lastly, we provide evidence that measurable residual disease negativity and an mutation predict a significant survival benefit outside clinical trials. Taken together, these data illuminate the real-world performance of venetoclax and decitabine or azacitidine in the treatment of AML.
近年来，急性髓系白血病（AML）的治疗模式发展迅速。与去甲基化药物单药治疗相比，维奈克拉与去甲基化药物联合使用在临床试验中延长了生存期。然而，鉴于安全性和疗效数据相互矛盾，对于维奈克拉方案在临床试验之外的表现知之甚少。对于去甲基化药物主干的影响了解更少。在本研究中，我们证明与阿扎胞苷-维奈克拉相比，地西他滨-维奈克拉与3级或更高等级血小板减少症的发生率显著更高相关，但淋巴细胞减少症的发生率更低。在整个队列中，ELN 2017细胞遗传学风险类别之间的缓解或生存没有差异。死于复发或难治性疾病的患者明显多于死于任何其他原因的患者。我们证明，Charlson合并症指数评分阈值为7可识别出极高风险患者，为临床使用提供了证据，以降低早期治疗相关死亡率的风险。最后，我们提供证据表明，可测量的残留病阴性和 突变预示着在临床试验之外有显著的生存益处。综上所述，这些数据阐明了维奈克拉与地西他滨或阿扎胞苷在治疗AML中的真实世界表现。
