SAN DIEGO – In newly diagnosed adults aged 18 to 60 years with acute myeloid leukemia (AML), idarubicin plus high-dose cytarabine (HDAC) with or without vorinostat was not superior to 7+3 chemotherapy, according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition.1
A majority of younger patients with AML receive initial therapy with 7+3 chemotherapy with an anthracycline and cytarabine, though there is a need for improved AML therapy beyond 7+3.
“A phase 2 study of vorinostat plus idarubicin and HDAC induction demonstrated an overall response rate of 85% and a 4% induction mortality rate,” said Guillermo Garcia-Manero, MD, department of leukemia, The University of Texas MD Anderson Cancer Center, Houston. “Therefore, we hypothesized that the addition of vorinostat to idarubicin plus HDAC is superior to 7+3 in younger patients with AML.”
For the phase 3 SWOG S1203 (ClinicalTrials.gov Identifier: NCT01802333), investigators enrolled 738 patients aged 18 to 60 years with previously untreated AML. Participants were randomly assigned 1:1:1 to receive 7+3 with daunorubicin plus cytarabine followed by HDAC consolidation, idarubicin plus HDAC and vorinostat induction, consolidation, and vorinostat maintenance, or idarubicin and HDAC induction and consolidation.
The complete remission and complete remission with incomplete marrow recovery rates were 75% with 7+3, 79% with idarubicin plus HDAC, and 77% with vorinostat (P = .58).
Significantly more patients received reinduction with 7+3 (24%) than those who received idarubicin plus HDAC (11%) and those who received idarubicin, cytarabine, and vorinostat (9%) (P = .001).
There were no significant differences in event-free survival, relapse-free survival, or overall survival between the 3 treatment arms, but Dr Garcia-Manero explained that 7+3 chemotherapy was superior to idarubicin plus cytarabine and idarubicin plus cytarabine and vorinostat in patients with favorable cytogenetics, potentially due to the use of lower doses of cytarabine consolidation.
The rates of toxicities related to therapy were significantly greater in the idarubicin arms compared with the 7+3 chemotherapy arm.
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“Future studies should include combination with nucleoside analogues, monoclonal antibodies, or targeted agents,” Dr Garcia-Manero concluded.
- Garcia-Manero G, Othus M, Pagel JM, et al. SWOG S1203: A randomized phase III study of standard cytarabine plus daunorubicin (7+3) therapy versus idarubicin with high dose cytarabine (IA) with or without vorinostat (IA+V) in younger patients with previously untreated acute myeloid leukemia (AML). Paper presented at: American Society of Hematology (ASH) 58th Annual Meeting and Exposition; December 3-6, 2016; San Diego, CA.