Abstract
We investigated whether homoharringtonine (HHT) added to venetoclax plus azacitidine (VA) could improve outcomes and counteract the negative effects of genetic patterns in patients with relapsed/refractory acute myeloid leukemia (RR-AML).
A multicenter retrospective cohort study of the response and genetic patterns of response to the VA plus HHT (VAH) versus the VA regimens as salvage treatment in patients with RR-AML was performed. The endpoints were the rates of composite complete remission, measurable residual disease, event-free survival, overall survival, and relapse between VAH and VA groups.
A total of 321 patients (VAH, n = 172; VA, n = 149) were analyzed. Compared with VA, VAH significantly improved the rates of composite complete remission (44.3% vs. 66.3%; P < 0.001), measurable residual disease negativity (34.8% vs. 59.3%; P = 0.002), prolonged overall survival (median: 15.1 months vs. not reached; P < 0.001), and event-free survival (median: 3.8 vs. 13.0 months; P < 0.001). VAH significantly mitigated the negative impact on VA efficacy of mutated FLT3-ITD/TKD, N/KRAS, and t(8;21)/AML1-ETO, as well as the relatively unfavorable effects of the TET2 and DNMT3A mutations. VAH significantly enhanced the response of patients with nonadverse European LeukemiaNet risk, with a trend toward improved response in those with adverse European LeukemiaNet risk, complex karyotype, and DNMT3A+FLT3+NPM1+. The incidence of grade 3 or higher adverse events was comparable between the two groups.
Our findings suggest the addition of HHT to VA might enhance response and mitigate the negative impact of certain genetic patterns in RR-AML while being well tolerated.
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