Todisco Elisabetta, Papayannidis Cristina, Fracchiolla Nicola, Petracci Elisabetta, Zingaretti Chiara, Vetro Calogero, Martelli Maria Paola, Zappasodi Patrizia, Di Renzo Nicola, Gallo Susanna, Audisio Ernesta, Griguolo Davide, Cerchione Claudio, Selleri Carmine, Mattei Daniele, Bernardi Massimo, Fumagalli Monica, Rizzuto Giuliana, Facchini Luca, Basilico Claudia Maria, Manfra Ilenia, Borlenghi Erika, Cairoli Roberto, Salutari Prassede, Gottardi Michele, Molteni Alfredo, Martini Vincenza, Lunghi Monia, Fianchi Luana, Cilloni Daniela, Lanza Francesco, Abruzzese Elisabetta, Cascavilla Nicola, Rivellini Flavia, Ferrara Felicetto, Maurillo Luca, Nanni Jacopo, Romano Alessandra, Cardinali Valeria, Gigli Federica, Roncoroni Elisa, Federico Vincenzo, Marconi Giovanni, Volpi Roberta, Sciumè Mariarita, Tarella Corrado, Rossi Giuseppe, Martinelli Giovanni
Divisione di Oncoematologia, IRCCS Istituto Europeo di Oncologia, Milano, Italy.
SC Ematologia, Ospedale Busto Arsizio, ASST Valle Olona, Varese, Italy.
Cancer. 2023 Apr 1;129(7):992-1004. doi: 10.1002/cncr.34608. Epub 2023 Jan 24.
Venetoclax in combination with hypomethylating agents (HMA) is revolutionizing the therapy of acute myeloid leukemia (AML). However, evidence on large sets of patients is lacking, especially in relapsed or refractory leukemia.
AVALON is a multicentric cohort study that was conducted in Italy on patients with AML who received venetoclax-based therapies from 2015 to 2020. The study was approved by the ethics committee of the participating institution and was conducted in accordance with the Declaration of Helsinki. The effectiveness and toxicity of venetoclax + HMA in 190 (43 newly diagnosed, 68 refractory, and 79 relapsed) patients with AML are reported here.
In the newly diagnosed AML, the overall response rate and survival confirmed the brilliant results demonstrated in VIALE-A. In the relapsed or refractory AML, the combination demonstrated a surprisingly complete remission rate (44.1% in refractory and 39.7% in relapsed evaluable patients) and conferred to treated patients a good expectation of survival. Toxicities were overall manageable, and most incidents occurred in the first 60 days of therapy. Infections were confirmed as the most common nonhematologic adverse event.
Real-life data show that the combination of venetoclax and HMA offers an expectation of remission and long-term survival to elderly, newly diagnosed patients, and to relapsed or chemoresistant AML, increasing the chance of cure through a different mechanism of action. The venetoclax + HMA combination is expected to constitute the base for triplet combinations and integration of target therapies. Our data contribute to ameliorate the understanding of venetoclax + HMA effectiveness and toxicities in real life.
维奈克拉联合低甲基化药物（HMA）正在彻底改变急性髓系白血病（AML）的治疗方法。然而，缺乏关于大量患者的证据，尤其是在复发或难治性白血病患者中。
AVALON是一项多中心队列研究，在意大利对2015年至2020年接受基于维奈克拉治疗的AML患者进行。该研究经参与机构的伦理委员会批准，并按照《赫尔辛基宣言》进行。本文报告了维奈克拉+HMA在190例（43例新诊断、68例难治性和79例复发性）AML患者中的有效性和毒性。
在新诊断的AML中，总体缓解率和生存率证实了VIALE-A研究中所展示的出色结果。在复发或难治性AML中，该联合治疗显示出惊人的完全缓解率（难治性患者中为44.1%，复发可评估患者中为39.7%），并赋予治疗患者良好的生存期望。毒性总体上是可控的，大多数不良事件发生在治疗的前60天。感染被确认为最常见的非血液学不良事件。
真实世界数据表明，维奈克拉与HMA联合使用为老年新诊断患者以及复发或化疗耐药的AML患者提供了缓解和长期生存的期望，通过不同的作用机制增加了治愈的机会。维奈克拉+HMA联合治疗有望成为三联组合和靶向治疗整合的基础。我们的数据有助于加深对维奈克拉+HMA在现实生活中的有效性和毒性的理解。
