Treatment Initiation of Venetoclax in Combination with Azacitidine or Decitabine in an Outpatient Setting in Patients with Untreated Acute Myeloid Leukemia

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.1265-1265
• Main Authors: Manda, Sudhir, Anz, Bertrand, Benton, Christopher, Broun, E. Randolph, Yimer, Habte, Renshaw, John, Geils, George F., Cruz, Jose, Fanning, Suzanne, Melear, Jason, Sharman, Jeff P., Kang, Kingston, Svensson, Anders, Pai, Madhavi, Donnellan, William
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-144886

Background: Venetoclax (Ven), a highly selective BCL-2 inhibitor, combined with azacitidine (Aza) suppresses oxidative phosphorylation, which selectively targets leukemia stem cells that drive initiation and perpetuation of acute myeloid leukemia (AML; Pollyea. Nat Med. 2018;24:1859), an aggressive malignancy most common in older adults. Safety and efficacy of Ven combined with the hypomethylating agents (HMA) Aza or decitabine (Dec) for the treatment of newly diagnosed AML in patients (pts) who are ineligible to receive intensive chemotherapy has been demonstrated (DiNardo. Blood. 2019;133:7; DiNardo. N Engl J Med. 2020;383:617). Phase 1 and Phase 3 studies initiated Ven + HMA in an inpatient setting due to the nature of the study design and concerns of tumor lysis syndrome (TLS) based on chronic lymphocytic leukemia treatment with Ven. Safety and efficacy of Ven + HMA treatment initiation in an exclusively outpatient setting is being evaluated in an ongoing Phase 3b, single-arm, multicenter, open-label study (NCT03941964). Here, we present pt baseline (BL) characteristics and safety during initial outpatient dose ramp-up of Ven + HMA. Methods: Pts with untreated AML with an ECOG performance status of 0-3 who were ineligible to receive intensive chemotherapy, had no evidence of spontaneous TLS at BL, and deemed an appropriate candidate for outpatient initiation of Ven + HMA by the investigator were eligible. Enrolled pts received Ven (100 mg on Cycle [C] 1 Day [D] 1, 200 mg C1D2, 400 mg C1D3-D28, and 400 mg daily for each 28-day cycle thereafter) in combination with Aza (75 mg/m 2 intravenously [IV] or subcutaneously for 7 days) or Dec (20 mg/m 2 IV for 5 days), beginning on D1 of each cycle, as per institutional practice, for ≤6 cycles. After the study period ended, pts could continue receiving commercially acquired standard-of-care treatments with Ven and Aza or Dec. Ven dosing was modified for concomitant use with moderate and strong CYP3A inhibitors (CYP3Ai). Ven and HMA dosing adjustments were permitted for the management of adverse events (AEs). TLS prophylaxis was initiated in all pts before the first dose of study drug or first new escalated dose. Pts were screened for BL TLS markers. BL AML characteristics, such as blast count and cytogenetics, were examined. The incidence of TLS per Howard Criteria (Howard. N Engl J Med. 2011;364:1844) was assessed for 5 days starting after the first dose of Ven. Results: At the data cutoff (April 30, 2021), 53