(031) Cladribine, Low-Dose Cytarabine, and Venetoclax versus Hypomethylating Agent and Venetoclax Induction in Newly Diagnosed Acute Myeloid Leukemia Patients Ineligible for Intensive Induction

Poster Abstract:

Background: Acute myeloid leukemia (AML) occurs primarily in older adults, with a median age of 68 years at diagnosis. However, older patients are often ineligible to receive standard intensive induction chemotherapy due to an increased frequency of comorbidities. Standard intensive therapy in patients >60 years has also been associated with poor outcomes and additional treatment-related complications due to the increased prevalence of unfavorable cytogenetics and antecedent myelodysplasia. Venetoclax combined with hypomethylating agents (HMAs) is a preferred regimen per NCCN guidelines for older patients unable to receive intensive induction therapy due to the favorable response rates and safety outcomes. A novel lower-intensity regimen of cladribine (Clad), low-dose cytarabine (LDAC), and venetoclax in a phase II study by Kadia et al. has demonstrated efficacy in patients ≥60 years with newly diagnosed AML, with a composite complete response (CR) rate of 93% and a negative measurable residual disease (MRD) rate of 84%. This has led to increased use of the Clad/LDAC/venetoclax regimen in newly diagnosed AML patients ineligible for intensive induction at our institution in recent years.

Objective: To compare the efficacy and safety of Clad/LDAC/venetoclax induction with HMA/venetoclax in older patients with previously untreated AML.

Methods: In this single-center retrospective cohort study, we compared the efficacy and safety outcomes of the two induction regimens in older patients (≥60 years) with previously untreated AML. For the Clad/LDAC/venetoclax cohort, induction consisted of a 28-day course of cladribine 5 mg/m2 IV daily on days 1-5, LDAC 20 mg/m2 IV daily on days 1-10, and oral venetoclax 400 mg daily on days 1-21 (ramp-up optional). For the HMA/venetoclax cohort, induction consisted of a 28-day course of azacitadine 75 mg/m2 IV/SC daily on days 1-7 or decitabine 20 mg/m2 IV daily on days 1-5 combined with oral venetoclax 400 mg daily on days 1-28 (ramp-up optional). Dose reductions were allowed based on performance status and organ function at the discretion of the provider. The venetoclax target dose of 400 mg was adjusted for drug interactions. Re-induction was considered if the bone marrow biopsy demonstrated inadequate response. Patients that responded proceeded to receive consolidation and/or allogeneic hematopoietic stem cell transplantation. The primary endpoint was composite CR rate [CR plus CR with incomplete blood count recovery (CRi)]. Secondary endpoints included MRD negativity, progression-free survival, overall survival, and safety outcomes. Standard statistical tests will be used.

Results: Pending

Conclusion/

Discussion: Pending

References (must also be included in final poster): 1. Pollyea DA, Altman JK, Assi R, et al. Acute Myeloid Leukemia, Version 3.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023;21(5):503-513. doi:10.6004/jnccn.2023.0025

2. Kadia TM, Reville PK, Wang X, et al. Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. J Clin Oncol. 2022;40(33):3848-3857. doi:10.1200/JCO.21.02823