Real-World Results of Different Venetoclax-Containing Regimens As Induction Therapy in Acute Myeloid Leukemia: A Single-Center Retrospective Study
Authors: Zhou Minran , Liu Zhenyi , Jiang Xinwen , Li Shijie , Ji Qingli , Liu Xiaohan , Zheng Yueyue , Meng Qing , Hu Dongmei , Yu Yuan , Wang Ran , Ma Sai , Chunyan Chen 
Published: December 2024

Objective: The objective of this retrospective study was to assess the effectiveness and safety of venetoclax (VEN) in combination with hypomethylating agents (HMA) or intensive chemotherapy (IC) as induction therapy in acute myeloid leukemia (AML) in real-world settings.
Methods: This study included 100 newly diagnosed AML patients in total, who were Ferrara criterion disaccorded, previously untreated, received at least one cycle of VEN plus HMAs or chemotherapy. Overall, 71 received VEN plus HMAs (mainly AZA) and 29 received short-term VEN (mainly 7days) plus IC (mainly IA) as induction therapy. If co-medicated with a mandatory CYP3A4 inhibitor for fungal prophylaxis (primarily voriconazole), VEN was administered at a dose of 100 mg instead of 400 mg. The response outcomes were composite complete remission (CRc) rate after one cycle of treatment and measurable residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) achieved negativity, with a sensitivity≥0.01%. Adverse events (AEs) were graded according to the CTCAE5.0.
Results:Baseline characteristics were similarly distributed between VEN + HMAs and VEN + IC group, includingECOG score, Blood routine, percentage of blast cells, FAB stratiﬁcation, and ELN risk stratification. The CRc rate was 77.5% and 93.1% in VEN + HMAs and VEN + IC group respectively (P=0.065). In favorable risk, intermediate risk and adverse risk subgroups, the CRc rates were 75.0%vs100.0%, 84.2%vs100.0%, and 69.0%vs77.8% in tow groups respectively. MRD data after one treatment cycle was available for 51 and 27 patients with CRc in VEN + HMAs group and VEN + IC group, respectively. The MRD-negative response rate was 70.6% and 92.6%, respectively (P=0.025).The MRD-negative response rates in favorable risk, intermediate risk and adverse risk subgroups were100.0%vs100.0%, 69.0%vs87.5%, 68.4%vs100.0% respectively. The most common AEs of any grade included neutropenia, anemia, thrombocytopenia, and lung infection. The incidence of Grade≥3 AEs in the two groups were neutropenia (36.6%vs69.0%, P=0.003), anemia (31.0%vs55.2%, P=0.024), thrombocytopenia (19.7%vs48.3%, P=0.004), and lung infection (15.5%vs65.5%, P&lt;0.001). Besides, the median hospitalization days of VEN + HMAs group was much shorter than VEN + IC group, with 21.8 days and 27.3 days respectively (P=0.001).
Conclusion: Although MRD negative rate in VEN + IC was better than VEN + HMAs group, there were no significant difference of CRc rate in two group. Further subgroup analysis was found that, in favorable risk, intermediate risk and adverse risk groups, the rates of CRc and MRD-negative response in two groups were similar. However, incidence of hematologic adverse events and infection rates were significantly lower in VEN + HMAs group compared to VEN + IC group. These results suggest that fit adult AML patients could benefit from VEN plus HMAs induction therapy with the encouraging remission rate and the low incidence of adverse events.