Posted: Friday, April 30, 2021
Stuart A. Rushworth, PhD, of the University of East Anglia, Norwich, United Kingdom, and colleagues performed a study to investigate whether inhibiting CD38 with daratumumab and BCL2 with venetoclax might prove to be more effective in treating acute myeloid leukemia (AML) than either agent alone. The investigators discovered that this treatment combination was, in fact, beneficial in terms of tumor reduction. Their preclinical research was presented during the virtual edition of the American Association for Cancer Research (AACR) Annual Meeting 2021 (Abstract 1048).
“Combining treatment with daratumumab and venetoclax in vivo significantly reduced tumor burden and improved animal survival compared to control or single agent,” concluded the study authors. “These data support that the combination treatment could have an important clinical application in the treatment of AML.”
Previously, these researchers demonstrated that daratumumab seems to inhibit the mitochondrial transfer from mesenchymal stromal cells to AML blasts, which promotes cancer growth. This study measured CD38 and BCL2 expression from primary AML blasts and mesenchymal stromal cells that were isolated from patient bone marrow. Compared with normal CD34-positive progenitor cells, BCL2 expression was significantly higher in AML blasts; CD38 expression was also increased.
The investigators used a xenograft mouse model of AML, and the effect of this combination regimen was assessed in vivo. Mice were engrafted with patient-derived AML or MV411-luc and treated with vehicle control, daratumumab alone, venetoclax alone, or their combination. Following treatment with venetoclax alone, cell viability was significantly reduced; daratumumab alone or combined with venetoclax did not seem to impact AML survival further. However, when daratumumab was used in combination with venetoclax, the researchers observed significantly more apoptosis in AML cells than in cells treated with a single agent.
Disclosure: For full disclosures of the study authors, visit abstractsonline.com.