TY - JOUR
T1 - Reduced dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia following intensive or low-intensity induction
T2 - a single-centre, single-arm, phase 2 trial
AU - Bazinet, Alexandre
AU - Kantarjian, Hagop
AU - Bataller, Alex
AU - Pemmaraju, Naveen
AU - Borthakur, Gautam
AU - Chien, Kelly
AU - Alvarado, Yesid
AU - Bose, Prithviraj
AU - Jabbour, Elias
AU - Yilmaz, Musa
AU - DiNardo, Courtney
AU - Issa, Ghayas
AU - Montalban-Bravo, Guillermo
AU - Short, Nicholas
AU - Sasaki, Koji
AU - Bull-Linderman, Debra
AU - Daver, Naval
AU - Garcia-Manero, Guillermo
AU - Ravandi, Farhad
AU - Kadia, Tapan
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2024/4
Y1 - 2024/4
N2 - Background: Patients with acute myeloid leukaemia have high rates of relapse, especially if they are unable to complete standard consolidation strategies or allogeneic haematopoietic stem-cell transplantation (HSCT). The phase 3 QUAZAR AML-001 study showed an overall survival benefit with oral azacitidine maintenance. The BCL2 inhibitor venetoclax is highly active in acute myeloid leukaemia and synergistic with azacitidine. We aimed to evaluate the efficacy and safety of low dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia. Methods: We performed a single-centre, single-arm, phase 2 study at the University of Texas MD Anderson Cancer Center in the USA. Eligible patients were adults (aged ≥18 years) with a WHO 2016 diagnosis of acute myeloid leukaemia in complete remission or complete remission with incomplete blood count recovery following intensive or low-intensity induction and not immediately eligible for HSCT. Eastern Cooperative Oncology Group performance status had to be 3 or less. Patients were assigned to maintenance therapy with azacitidine 50 mg/m2 intravenously or subcutaneously for 5 days and venetoclax 400 mg orally for 7 days or 14 days. The primary outcome was relapse-free survival. The study was closed early due to slow accrual. All patients were included in the efficacy and safety analyses. This trial is registered with ClinicalTrials.gov (NCT04062266). Findings: Between Sept 26, 2019, and Oct 26, 2022, 35 patients were enrolled, of whom 25 (71%) were assigned to cohort 1 following intensive induction and ten (29%) to cohort 2 following low-intensity induction. Of 35 patients, 18 (51%) were male and 17 (49%) were female. The median age was 55 years (IQR 41–62). The median number of cycles given was 9 (IQR 2–22) and median follow-up time was 23·3 months (IQR 9·0–30·0). The median relapse-free survival was not reached (95% CI 20·2 to not calculable) in the full cohort, not reached (29·1 to not calculable) in cohort 1, and 30·3 months (16·5 to not calculable) in cohort 2. The 2-year relapse-free survival was 65% (95% CI 50–85) in the full cohort, 71% (53–94) in cohort 1, and 52% (27–100) in cohort 2. The most common grade 3–4 treatment-emergent adverse events were thrombocytopenia (n=6), lung infection (n=4), leukopenia (n=4), and neutropenia (n=3). No deaths occurred during maintenance therapy. Interpretation: Low dose azacitidine plus venetoclax is a feasible maintenance strategy in acute myeloid leukaemia following intensive and low-intensity induction. Funding: University of Texas MD Anderson Cancer Center, MDS/AML Moon Shot, Genentech.
AB - Background: Patients with acute myeloid leukaemia have high rates of relapse, especially if they are unable to complete standard consolidation strategies or allogeneic haematopoietic stem-cell transplantation (HSCT). The phase 3 QUAZAR AML-001 study showed an overall survival benefit with oral azacitidine maintenance. The BCL2 inhibitor venetoclax is highly active in acute myeloid leukaemia and synergistic with azacitidine. We aimed to evaluate the efficacy and safety of low dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia. Methods: We performed a single-centre, single-arm, phase 2 study at the University of Texas MD Anderson Cancer Center in the USA. Eligible patients were adults (aged ≥18 years) with a WHO 2016 diagnosis of acute myeloid leukaemia in complete remission or complete remission with incomplete blood count recovery following intensive or low-intensity induction and not immediately eligible for HSCT. Eastern Cooperative Oncology Group performance status had to be 3 or less. Patients were assigned to maintenance therapy with azacitidine 50 mg/m2 intravenously or subcutaneously for 5 days and venetoclax 400 mg orally for 7 days or 14 days. The primary outcome was relapse-free survival. The study was closed early due to slow accrual. All patients were included in the efficacy and safety analyses. This trial is registered with ClinicalTrials.gov (NCT04062266). Findings: Between Sept 26, 2019, and Oct 26, 2022, 35 patients were enrolled, of whom 25 (71%) were assigned to cohort 1 following intensive induction and ten (29%) to cohort 2 following low-intensity induction. Of 35 patients, 18 (51%) were male and 17 (49%) were female. The median age was 55 years (IQR 41–62). The median number of cycles given was 9 (IQR 2–22) and median follow-up time was 23·3 months (IQR 9·0–30·0). The median relapse-free survival was not reached (95% CI 20·2 to not calculable) in the full cohort, not reached (29·1 to not calculable) in cohort 1, and 30·3 months (16·5 to not calculable) in cohort 2. The 2-year relapse-free survival was 65% (95% CI 50–85) in the full cohort, 71% (53–94) in cohort 1, and 52% (27–100) in cohort 2. The most common grade 3–4 treatment-emergent adverse events were thrombocytopenia (n=6), lung infection (n=4), leukopenia (n=4), and neutropenia (n=3). No deaths occurred during maintenance therapy. Interpretation: Low dose azacitidine plus venetoclax is a feasible maintenance strategy in acute myeloid leukaemia following intensive and low-intensity induction. Funding: University of Texas MD Anderson Cancer Center, MDS/AML Moon Shot, Genentech.
UR - http://www.scopus.com/inward/record.url?scp=85188839345&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85188839345&partnerID=8YFLogxK
U2 - 10.1016/S2352-3026(24)00034-6
DO - 10.1016/S2352-3026(24)00034-6
M3 - Article
C2 - 38548404
AN - SCOPUS:85188839345
SN - 2352-3026
VL - 11
SP - e287-e298
JO - The Lancet Haematology
JF - The Lancet Haematology
IS - 4
ER -