Homoharringtonine overcomes the negative impact of genetic patterns on venetoclax plus azacitidine regimen in relapsed/refractory acute myeloid leukemia: a multi-center, cohort study

Abstract

Abstract Background The response of venetoclax (VEN)-based therapy is closely associated with genetic patterns and combining regimens in acute myeloid leukemia (AML). Whether other agents added to VEN plus hypomethylating agents (HMA) regimen could overcome the negative impact of genetic patterns on response remains unclear. Methods A multi-center, cohort study of the response and the genetic patterns of response of VEN plus AZA and HHT (VAH) versus VEN plus AZA (VA) regimens as salvage treatment in the patients with RR-AML was performed. Patients were enrolled from four studies from October 2018 to December 2022 at nine medical centers in china. The endpoints in this study were to evaluate the rate of composite complete remission (CRc), measurable residual disease (MRD), event-free survival (EFS), overall survival (OS) and relapse between VAH and VA groups. Results A total of 321 patients were analyzed, including 150 females and 171 males, with a median age at 46 (IQR, 35–61) years. There were 172 patients in the VAH and 149 in the VA group. VAH significantly improved CRc rate (66.3% vs. 44.3%, P < 0.001) and prolonged OS (median OS, not reach vs. 14.3 months, P = 0.004), to compared with VA. VAH significantly overcame the negative impact of FLT3-ITD/TKD, N/KRAS, TET2, DNMT3A mutations, and t(8;21)/AML1-ETO, as well as non-adverse ELN risk, also apparently in adverse ELN risk or complex karyotype, on the response of VA regimen. Conclusion The impact of genetic patterns on the response presented diversely in different VEN-based regimens. HHT added to VA regimen might improve the response and overcome the negative impact of part genetic patterns in RR-AML.