Venetoclax Plus Azacitidine for Newly Diagnosed Younger Acute Myeloid Leukemia Patients Independent of Fitness for Intensive Chemotherapy

作者：Justin M. Watts, Connor Sohalski, Alessia Zoso, Jessica Dell-Martin, Ayele Belachew, Diana Abbott, Maria L. Amaya, Andrew Kent, Christine M. McMahon, Marc Schwartz, Mikkael A. Sekeres, Clayton A. Smith, Sangeetha Venugopal, Craig T. Jordan, Mary Berg, Mary Haag, Nicholas Willard, Dara L. Aisner, Jeffrey Schowinsky, Zenggang Pan, Jingjing Zhang, Jonathan A. Gutman, Daniel A. Pollyea · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-199267 · 被引用次数：5 · 研究领域：Acute Myeloid Leukemia Research、Myeloproliferative Neoplasms: Diagnosis and Treatment、Chronic Myeloid Leukemia Treatments

Background Venetoclax (ven) with azacitidine (aza) is the standard of care for newly diagnosed acute myeloid leukemia (AML) patients unfit for intensive chemotherapy (IC) due to age or comorbidities. However, fit patients with poor-risk disease biology may not benefit from IC. Furthermore, adverse risk factors for IC are not necessarily adverse risk factors for ven/aza. Therefore, we designed a pilot study of ven/aza for newly diagnosed younger AML patients with non-favorable risk disease. Methods This is a prospective, single-arm, multi-institutional investigator-initiated trial (NCT03573024). Newly diagnosed AML patients aged 18-59 with ELN 2017 non-favorable risk disease were enrolled (initially only adverse risk patients were permitted; after five years intermediate risk patients were allowed). Of 36 subjects planned, 32 have enrolled. Stopping rules for futility based on responses were planned. Subjects were matched 1:1 to historical controls who received IC based on age and ELN risk for this analysis. Subjects received aza 75mg/m2 IV d1-7 of a 28-day cycle. Ven was escalated to 600mg on days 1-4 and continued x 28 days. Interruptions to allow count recovery between cycles, with growth factor as needed, occured. Subjects had to achieve complete remission (CR), CRi or morphologic leukemia free state (MLFS) by cycle 2 to continue on study. After at least MLFS, subjects could receive up to 3 additional cycles. Once subjects achieved MRD negativity, they could receive MRD-ne...