Molica Matteo, Perrone Salvatore, Federico Vincenzo, Alati Caterina, Molica Stefano, Rossi Marco
Department of Hematology-Oncology, Azienda Universitaria Ospedaliera Renato Dulbecco, 88100 Catanzaro, Italy.
Department of Hematology, Polo Universitario Pontino, S.M. Goretti Hospital, 04100 Latina, Italy.
Cancers (Basel). 2023 Dec 22;16(1):73. doi: 10.3390/cancers16010073.
The combination approach based on venetoclax (VEN) with azacytidine (AZA) has significantly improved outcomes for elderly patients with acute myeloid leukemia (AML). This innovative approach has led to higher rates of overall response, measurable residual disease (MRD)-negative remissions, and overall survival compared with AZA monotherapy. As a result, this combination has emerged as the gold-standard treatment for elderly or unfit patients with AML who are not eligible for intensive therapy. In younger, fit patients with AML, intensive induction and consolidation chemotherapy is commonly used as a first-line approach; however, relapse continues to be the main reason for treatment failure in approximately 30-40% of patients. Efforts to improve MRD-negative response rates and to facilitate the transition to allogeneic hematopoietic stem cell transplantation, particularly in high-risk AML, have inspired trials exploring the combination of intensive chemotherapy with targeted agents. VEN, a first-in-class anti-BCL2 agent, combined with intensive chemotherapy regimens has shown deep MRD-negative remissions, producing prolonged event-free survival and enhancing the transition to allogeneic transplant in first-complete-remission patients. These benefits support the incremental advantages of adding VEN to intensive chemotherapy approaches across ELN risk subcategories, and provides a robust benchmark to design future trials. In this review, we will discuss current studies assessing the efficacy of frontline regimens integrating VEN into intensive chemotherapy in younger patients with AML and specific molecularly defined subgroups.
基于维奈克拉（VEN）与阿扎胞苷（AZA）的联合治疗方法显著改善了老年急性髓系白血病（AML）患者的治疗效果。与阿扎胞苷单药治疗相比，这种创新方法带来了更高的总体缓解率、可测量残留病（MRD）阴性缓解率和总生存率。因此，这种联合治疗已成为不符合强化治疗条件的老年或身体状况不佳的AML患者的金标准治疗方法。在年轻、身体状况良好的AML患者中，强化诱导和巩固化疗通常作为一线治疗方法；然而，复发仍然是约30%-40%患者治疗失败的主要原因。提高MRD阴性缓解率以及促进向异基因造血干细胞移植过渡的努力，特别是在高危AML患者中，促使人们开展了探索强化化疗与靶向药物联合应用的试验。维奈克拉是一流的抗BCL2药物，与强化化疗方案联合应用已显示出深度MRD阴性缓解，可延长无事件生存期，并提高首次完全缓解患者向异基因移植过渡的比例。这些益处支持了在欧洲白血病网（ELN）风险亚组中，将维奈克拉添加到强化化疗方法中的增量优势，并为设计未来试验提供了有力的基准。在本综述中，我们将讨论当前评估将维奈克拉纳入年轻AML患者强化化疗的一线方案以及特定分子定义亚组疗效的研究。
