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

Objective: Whether other agents added to venetoclax (VEN) plus hypomethylating agents (HMA) regimen could overcome the negative impact of genetic patterns on response in patients with relapsed/refractory acute myeloid leukemia (RR-AML) remains unclear. Aim of this study was to evaluate whether homoharringtonine (HHT) added to VEN plus azacitidine (AZA) regimen could improve the response and overcome the negative impact of genetic patterns in patients with RR-AML . 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. 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. Multivariate analysis showed that VAH was the independently protective factor for CRc and survival. In addition, 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. Key words: homoharringtonine, venetoclax, relapsed/refractory, acute myeloid leukemia, genetic pattern