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Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Posted: Tuesday, May 14, 2024
For elderly patients with multiple myeloma, combination therapy with the demethylase inhibitor azacitidine and the B-cell lymphoma-2 (BCL2) antagonist venetoclax may be a feasible therapeutic option, according to a study published in Haematologica. Additional studies are warranted to assess the efficacy and safety of this novel steroid-free combination therapy in multiple myeloma, explained Tríona Ní Chonghaile, PhD, of the Royal College of Surgeons in Ireland, Dublin, and colleagues. The next step, the investigators stated, is to assess the efficacy and safety of this combination therapy in a clinical trial setting.
“This research is a significant step in identifying more effective treatment options for multiple myeloma. By combining venetoclax and azacitidine, we’ve seen enhanced efficacy across a wide range of patient samples. It shows the benefits of re-evaluating existing treatments in new contexts to expand their potential,” commented Dr. Chonghaile in an institutional press release.
Bone marrow samples were obtained from patients with multiple myeloma to isolate CD138-positive cells. In addition, multiple myeloma cell lines were cultured and screened for epigenetic modifiers to induce BCL2 dependency and increase sensitivity to venetoclax. BH3 profiling and immunoprecipitation were also performed on multiple myeloma cell lines to identify the mechanism of synergy.
The study authors reported an increased extent of cellular death across several multiple myeloma cell lines after combination treatment with venetoclax and azacitidine. Furthermore, an increase in the expression of NOXA may explain the mechanism of synergy. Moreover, the addition of a steroid to the combination treatment regimen increased the death of immune cells and had a minimal impact on the extent of cell death. These findings emphasize the need for a steroid-sparing regimen to reduce negative outcomes in this patient population.
Disclosure: For full disclosures of the study authors, visit haematologica.org.
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