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RCSI research has found that venetoclax, a medication currently approved for leukaemia, has benefits for patients with multiple myeloma (MM) when used in combination with another drug. This discovery offers a new avenue of treatment options for the currently incurable disease.
MM is newly diagnosed in around 400 people in Ireland each year. Despite treatment advances in recent years, it remains incurable. The search for innovative treatment strategies is crucial, particularly for patients whose cancer is resistant to standard care.
In the new study published in Haematologica, researchers at the RCSI Department of Physiology and Medical Physics and the Beaumont RCSI Cancer Centre set out to identify complementary drugs that would enhance the efficiency of venetoclax, a drug approved for use in leukaemia, for MM treatment. Although previously tested in MM, venetoclax, which blocks the function of a protein called BCL-2, was only found to be effective for a small proportion of patients.
The researchers discovered that combining venetoclax with the demethylase inhibitor 5-azacytidine significantly increased its effectiveness across many MM cell lines, indicating a broader potential patient population that could be treated with the new combination.
Overall, the data identifies 5-azacytidine and venetoclax as an effective treatment combination, which could be a tolerable steroid-sparing regimen, particularly for elderly MM patients.
“This research is a significant step in identifying more effective treatment options for multiple myeloma. By combining venetoclax and 5-azacytidine we have 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,” said Prof Tríona Ní Chonghaile, Associate Professor and research lead, RCSI Department of Physiology and Medical Physics.
Prof Siobhán Glavey, Chair, RCSI Department of Pathology and Clinician Scientist, Beaumont RCSI Cancer Centre commented: “Discovering the potential of this new drug combination is a promising development. Our next goal is to test for efficacy and safety for multiple myeloma in a clinical trial setting to bring us closer to offering a new treatment strategy for patients.”
The mechanism of how the two drugs work efficiently together was also investigated and it was shown that the combination of the two therapies was effective in patient samples from different stages of cancer, even if that patient had been previously treated with chemotherapy drugs.
Reference
Flanagan L, Coughlan A, Cosgrove N, Roe A, Wang Y, Gilmore S, et al. Leukaemia Research Foundation; Science Foundation Ireland; Breakthrough Cancer Research. Steroid-free combination of 5-azacytidine and venetoclax for the treatment of multiple myeloma. Haematologica. 2024 Mar 21. doi: 10.3324/haematol.2023.283771
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