Real-World Experience of Venetoclax Target Dosing with Concomitant Posaconazole in Adult Patients with Acute Myeloid Leukemia

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.2432-2432
• Main Authors: Freeman, Tracelyn, Habib, Alma, Huang, Ying, Kumar, Pooja, Waller, Allyson, Fleming, Megan, McMillan, Kelsey, Hartzler, Natalia, Behbehani, Gregory K, Blachly, James S., Blaser, Bradley Wayne, Borate, Uma, Eisfeld, Ann-Kathrin, Grieselhuber, Nicole R., Larkin, Karilyn T., Lee, Shinae, Long, Meixiao, Mims, Alice, Srisuwananukorn, Andrew, Sahasrabudhe, Kieran D, Koenig, Kristin L
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-203704

Introduction: Venetoclax (VEN) in combination with a hypomethylating agent (HMA) or low-dose cytarabine (LDAC), provides patients with acute myeloid leukemia (AML) a less intensive treatment option that has shown to be efficacious. However, this regimen creates potential challenges in management of toxicities and drug interactions, particularly in the presence of azole antifungals. Posaconazole (POSA) is a preferred prophylactic agent but introduces complexity due to its strong inhibition of the CYP3A4 enzyme and p-glycoprotein transporter affecting VEN metabolism leading to increased blood concentrations. As such, the optimal approach for dosing VEN with concurrent POSA is debatable and remains unknown. In 2021, our institution adopted the adjustment of VEN 100mg daily with POSA, mirroring other strong CYP3A4 inhibitors, but this is an increase from the recommended target dose of 70mg. Herein, we investigated the safety of VEN 100mg daily in comparison to VEN 70mg daily when administered concomitantly with POSA and aimed to provide a real-world clinical evaluation of these two proposed dosing strategies. Methods: Adult patients with newly diagnosed (ND) or relapsed/refractory (R/R) AML treated with VEN 100mg or 70mg and HMA/LDAC plus concurrent POSA at The Ohio State University Comprehensive Cancer Center between November 2018 and February 2024 were included in this single-center retrospective cohort study. Eligible patients received a minimum of seven days of chemotherapy and at least one dose of POSA. Primary safety composite endpoints were incidence/duration of cytopenias and incidence of tumor lysis syndrome (TLS) during the first cycle. Secondary endpoints included combined complete remission (CR), CR with incomplete count recovery (CRi), and CR with partial hematologic recovery (CRh) within the first two cycles. The comparison between VEN 100mg and 70mg was conducted using chi-squared test or Fisher's exact test. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Results: A total of 145 patients were included; 113 patients received VEN 100mg and 32 patients received 70mg. Baseline demographics were well-balanced between groups. Median age was 69.5 years, 56% were male, 60% had a performance status (Eastern Cooperative Oncology Group) of 1 at treatment start, and median follow-up was 13.2 months. Disease type was depicted by primary AML in 63.5%, ND in 69.0%, and complex karyotype in 28.5% of the tota