TY - JOUR
T1 - Aspacytarabine for the treatment of patients with AML unfit for intensive chemotherapy
T2 - a phase 2 study
AU - Altman, Jessica K.
AU - Zuckerman, Tsila
AU - Koprivnikar, Jamie
AU - McCloskey, James
AU - Kota, Vamsi
AU - Keng, Michael
AU - Frankfurt, Olga
AU - Abaza, Yasmin
AU - Bixby, Dale L.
AU - Emadi, Ashkan
AU - Burch, Micah
AU - Bhatnagar, Bhavana
AU - Luger, Selina M.
AU - Percival, Mary Elizabeth
AU - Wolach, Ofir
AU - Craig, Michael
AU - Ganzel, Chezi
AU - Roboz, Gail
AU - Levi, Itai
AU - Gourevitch, Anna
AU - Flaishon, Liat
AU - Tessler, Shoshi
AU - Blumberg, Chen
AU - Gengrinovitch, Stela
AU - Yakar, Ruth Ben
AU - Rowe, Jacob M.
N1 - Publisher Copyright:
© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
PY - 2023/12/26
Y1 - 2023/12/26
N2 - High-dose cytarabine is associated with gastrointestinal and cerebellar toxicity, precluding its use for older or unfit patients with acute myeloid leukemia (AML). Aspacytarabine, an inactive prodrug of cytarabine, was evaluated as monotherapy in a phase 2b study of patients unfit for intensive chemotherapy (NCT03435848). Sixty-five patients with AML were treated with aspacytarabine 4.5 g/m2 per day (equimolar to 3 g/m2 per day cytarabine) for 6 doses per treatment. The median age was 75 years; 60.6% of patients had de novo AML, 28.8% had AML secondary to myelodysplastic syndrome, and 10.6% had therapy-related AML. Overall, 36.9% achieved complete remission (CR) with full count recovery. CR rates in patients with secondary AML, patients with prior treatment with hypomethylating agents, and patients with TP53 mutation were 26.7%, 25%, and 36%, respectively. Median overall survival was 9 months (range, 6-15.9) and was not reached among responders. Hematologic recovery was observed in all responding patients by day 26 without prolonged cytopenias. Adverse events typically precluding the use of high-dose cytarabine in older or unfit patients were not observed. These data suggest that aspacytarabine may be an effective regimen with a reduction in the attendant toxicities associated with high-dose cytarabine, an important consideration when treating AML and other hematologic disorders that use high-dose cytarabine. This trial was registered at www.clinicaltrials.gov as #NCT03435848.
AB - High-dose cytarabine is associated with gastrointestinal and cerebellar toxicity, precluding its use for older or unfit patients with acute myeloid leukemia (AML). Aspacytarabine, an inactive prodrug of cytarabine, was evaluated as monotherapy in a phase 2b study of patients unfit for intensive chemotherapy (NCT03435848). Sixty-five patients with AML were treated with aspacytarabine 4.5 g/m2 per day (equimolar to 3 g/m2 per day cytarabine) for 6 doses per treatment. The median age was 75 years; 60.6% of patients had de novo AML, 28.8% had AML secondary to myelodysplastic syndrome, and 10.6% had therapy-related AML. Overall, 36.9% achieved complete remission (CR) with full count recovery. CR rates in patients with secondary AML, patients with prior treatment with hypomethylating agents, and patients with TP53 mutation were 26.7%, 25%, and 36%, respectively. Median overall survival was 9 months (range, 6-15.9) and was not reached among responders. Hematologic recovery was observed in all responding patients by day 26 without prolonged cytopenias. Adverse events typically precluding the use of high-dose cytarabine in older or unfit patients were not observed. These data suggest that aspacytarabine may be an effective regimen with a reduction in the attendant toxicities associated with high-dose cytarabine, an important consideration when treating AML and other hematologic disorders that use high-dose cytarabine. This trial was registered at www.clinicaltrials.gov as #NCT03435848.
UR - http://www.scopus.com/inward/record.url?scp=85180946102&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85180946102&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2023010943
DO - 10.1182/bloodadvances.2023010943
M3 - Article
C2 - 37903324
AN - SCOPUS:85180946102
SN - 2473-9529
VL - 7
SP - 7494
EP - 7500
JO - Blood Advances
JF - Blood Advances
IS - 24
ER -