Response to HiDAC/mitoxantrone/venetoclax (HMV) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML).

Abstract

6527 Background: Outcomes for patients (pts) with R/R AML are dismal, especially after failure of Venetoclax (Ven)-based regimens. Effective strategies are urgently needed particularly in the absence of targetable mutations. An early-phase study of HMV demonstrated a 75% remission rate in pts with R/R AML, however the majority of these pts were Ven-naïve (Ruhnke et al, EHA 2024). We aimed to study a real-world cohort of pts with R/R AML treated with HMV. Methods: A retrospective cohort of 16 pts with R/R AML treated with HMV at the University of Chicago (2020–2025) was analyzed. Clinical and disease characteristics were collected; European Leukemia Net (ELN) 2022 criteria were used for risk stratification and response assessment. Overall response rate (ORR) was defined as complete response (CR) + CR with partial hematologic recovery (CRh) + CR with incomplete hematologic recovery (CRi). Overall survival (OS) was estimated using Kaplan-Meier methods. Results: Sixteen pts with R/R AML were included; 2 pts had ALL with lineage switch to AML. Median age at diagnosis was 54.5 years. Amongst the 14 pts with AML at initial diagnosis, 28.6%, 14.3%, and 50.0% had favorable, intermediate, and adverse ELN 2022 risk, respectively. Our cohort of pts was heavily pre-treated with 56.2% receiving ≥3 lines of therapy prior to HMV; two pts had received prior allogeneic hematopoietic stem cell transplant (allo-SCT). The ORR was 43.8%; in addition, 6.3% attained morphologic leukemia-free state (MLFS), 6.3% obtained a partial response (PR), and 43.7% had no response/not evaluable (NR/NE). Among pts that received prior intensive AML chemotherapy (n=8), the ORR was 50.0% with HMV. The ORR was 41.6% in pts with prior Ven exposure (n=12). Median OS from HMV initiation was 5.1 months (95% CI: 2.2-9.2) with two deaths within 30 days of HMV initiation; 62.5% of patients received subsequent therapy and 37.5% proceeded to allo-SCT. Two patients are alive in remission at time of data analysis; both underwent allo-SCT after HMV. Conclusions: In this heavily pretreated R/R AML cohort, HMV produced encouraging response rates and facilitated transition to allo-SCT in a subset of pts. These data warrant further evaluation of HMV as an R/R option even in pts with prior Ven exposure. Patient characteristics and efficacy outcomes. Median Age at Time of Receiving HMV (N=16) 54.5 years (Range 21-66) Gender (N=16) Male 69%; Female 31% # of Lines of Therapy Received Prior to HMV (N=16) 1 Line 25%; 2 Lines 18.8%; ≥3 Lines 56.2% Best Response to HMV (N=16) CR 31.2%; CRh 6.3%; CRi 6.3%; MLFS 6.3%; PR 6.3%; NR/NE 43.7% Best Response to HMV in Patients Who Received Prior AML-Based Intensive Chemotherapy (N=8) CR 25%; CRh 12.5%; CRi 12.5%; MLFS 0%; PR 0%; NR/NE 50% Best Response to HMV in Patients Who Received Prior Venetoclax (N=12) CR 25%; CRh 8.3%; CRi 8.3%; MLFS 0%; PR 8.3%; NR/NE 50%