Comparable outcomes with 14-, 21-, or standard 28-day venetoclax in the first cycle of azacitidine–venetoclax in untreated acute myeloid leukemia: real-world experience from the Hokkaido Leukemia Net
Minoru Kanaya, Masahiro Onozawa, Toshihiro Matsukawa, Naoki Miyashita, Fumiaki Fujii, Shota Yoshida, Jun Nagai, Masayuki Aiba, Daisuke Hidaka, Junichi Hashiguchi, Hajime Senjo, Tetsuyuki Igarashi, Masahiro Chiba, Satoshi Yamamoto, Taku Shimizu, Takashi Ishio, Shota Yokoyama, Ko Ebata, Satoshi Iyama, Tatsuo Oyake, Takeshi Kondo, Takanori Teshima
Abstract
Acute myeloid leukemia (AML) has a median age at diagnosis of 68 years, and many patients are deemed ineligible for intensive chemotherapy or allogeneic stem cell transplantation, resulting in a generally poor prognosis [ 1 ]. The pivotal VIALE-A randomized trial showed that Azacitidine (AZA) at 75 mg/m²/day for 7 days every 28 days, combined with once-daily continuous Venetoclax (VEN) at 400 mg for 28 days, significantly improved composite complete remission (CRc) rates (66.4% vs. 28.3%) and overall survival (OS) (14.7 vs. 9.6 months) compared to AZA alone [ 2 ]. The combination of AZA-VEN has become the standard treatment for unfit AML patients, demonstrating high efficacy in real-world settings as well [ 3 ]. However, prolonged neutropenia—which increases the risk of febrile neutropenia (FN) and documented infections—remains a major challenge during continuous AZA-VEN therapy. Several approaches have been explored to mitigate this issue, including VEN dose modification, therapeutic drug monitoring [ 4 ], and shortening of VEN administration duration [ 5 , 6 , 7 , 8 ]. Willekens C et al. demonstrated that VEN used for 7 days resulted in similar response rates and survival compared to standard 28 days of VEN exposure. In response to the literature written by Willekens C et al., we investigated the impact of reduced VEN duration for 14 days, 21 days, and 28 days by using a multi-institutional dataset from the Hokkaido Leukemia Net (HLN).