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

Authors

Tapan M Kadia
Patrick K Reville
Xuemei Wang
Caitlin R Rausch
Gautam Borthakur
Naveen Pemmaraju
Naval G Daver
Courtney D DiNardo
Koji Sasaki
Ghayas C Issa
Maro Ohanian
Guillermo Montalban-Bravo
Nicholas J Short
Nitin Jain
Alessandra Ferrajoli
Kapil N Bhalla
Elias Jabbour
Koichi Takahashi
Rashmi Malla
Kelly Quagliato
Rashmi Kanagal-Shamanna
Uday R Popat
Michael Andreeff
Guillermo Garcia-Manero
Marina Y Konopleva
Farhad Ravandi
Hagop M Kantarjian

Publication Date

11-20-2022

Journal

Journal of Clinical Oncology

Abstract

PURPOSE: The combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone. We hypothesized that the addition of venetoclax to cladribine (CLAD)/low-dose araC (low-dose cytarabine [LDAC]) alternating with 5-AZA backbone may further improve outcomes for older patients with newly diagnosed AML.

METHODS: This is a phase II study investigating the combination of venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA in older (≥ 60 years) or unfit patients with newly diagnosed AML. The primary objective was composite complete response (CR) rate (CR plus CR with incomplete blood count recovery); secondary end points were overall survival, disease-free survival (DFS), overall response rate, and toxicity.

RESULTS: A total of 60 patients were treated; median age was 68 years (range, 57-84 years). By European LeukemiaNet, 23%, 33%, and 43% were favorable, intermediate, and adverse risk, respectively. Fifty-six of 60 evaluable patients responded (composite CR: 93%) and 84% were negative for measurable residual disease. There was one death (2%) within 4 weeks. With a median follow-up of 22.1 months, the median overall survival and DFS have not yet been reached. The most frequent grade 3/4 nonhematologic adverse events were febrile neutropenia (n = 33) and pneumonia (n = 14). One patient developed grade 4 tumor lysis syndrome.

CONCLUSION: Venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA is an effective regimen among older or unfit patients with newly diagnosed AML. The rates of overall survival and DFS are encouraging. Further study of this non-anthracycline-containing backbone in younger patients, unfit for intensive chemotherapy, as well as comparisons to standard frontline therapies is warranted.

Keywords

Aged, Humans, Antineoplastic Combined Chemotherapy Protocols, Azacitidine, Bridged Bicyclo Compounds, Heterocyclic, Cladribine, Cytarabine, Leukemia, Myeloid, Acute, Middle Aged, Aged, 80 and over

Comments

Trial registration: ClinicalTrials.gov NCT03586609.

PMID: 35704787