Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster I
Hematology Disease Topics & Pathways:
AML, Diseases, Therapies, Combinations, Myeloid Malignancies, Clinically relevant
Primary AML blasts were isolated from patient’s BM. CD38 expression and BCL2 expression was assessed by flow cytometry analysis of AML. AML had significantly higher BCL2 expression and a slight increase in CD38 expression compared to CD34+ cells. Venetoclax alone caused a significant decrease in cell viability, however daratumumab or in combination with Venetoclax had no additive effect on AML survival. Since AML is highly reliant on the BM microevironment we cultured AML on MSC with either Venetoclax alone, daratumumab alone, or Venetoclax and daratumumab for 24 hours. Cells were then stained with Annexin V-FITC/PI and analysed using flow cytometry. Cells underwent significantly more apoptosis in the combination Venetoclax and daratumumab treatment when compared to control AML cells.
To determine the effect of Venetoclax and daratumumab treatment in preclinical models we used an NSG xenograft mouse model of AML, we transplanted MV411-luc or patient derived AML and treated the animals with either vehicle control (PBS) daratumumab (5mg/kg) on day 7 and 14 alone, Venetoclax (100mg/kg/day) alone, or both daratumumab and Venetoclax followed by bioluminescence imaging. In vivo, treatment with combination daratumumab and Venetoclax significantly reduced tumor burden and improved survival compared to control and either drug alone in the patient derived AML xenograft mouse model and in MV411.
These data support the further clinical investigation of Venetoclax and Daratumumab combination as a therapeutic approach for the treatment AML.
Disclosures: Bowles: AbbVie: Research Funding; Janssen: Research Funding. Rushworth: Janssen: Research Funding; AbbVie: Research Funding.
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