Patients with acute leukemia still have a poor prognosis and are mostly treated with potent chemotherapy combinations. However, new treatments are constantly being investigated and developed. The so-called BCL2 inhibitor, venetoclax, has shown promise as a new leukemia treatment in combination with azacitidine.
Leukemia cells produce high levels of a protein called BCL2, which helps them to survive in the bone marrow. Venetoclax inhibits the activity of BCL2 and sensitises cancer cells to programmed cell death. However, as is typical of new cancer treatment, this drug is not effective in all patients.
A clinical trial led by Mika Kontro, a specialist in haematology, performed in collaboration with the University of Helsinki, the HUS Cancer Centre and the Finnish Leukemia Group, aims to develop methods to identify patients with acute myeloid leukemia (AML) who are sensitive to venetoclax.
The first phase of the study focused on testing the feasibility of a laboratory-based drug sensitivity assay on the patient's own cells to identify patients sensitive to venetoclax. The results of the study have recently been published in the journal Haematologica.
Drug sensitivity testing has been shown in several previous studies to be a promising method for predicting treatment response in cancer patients. However, previous studies have suggested that differences in drug sensitivity testing methods can have a significant impact on the outcome. Therefore, one of the main objectives of the research team was to systemically evaluate which methods lead to the most reliable results.
The results now published show that drug sensitivity testing reliably predicts both patient response to treatment and patient prognosis.
“We spent a lot of time comparing different methods because their impact on drug response results turned out to be surprisingly large. We obtained the most accurate results when the drug sensitivity test was performed on so-called blast cells, i.e. immature leukemia cells isolated from bone marrow samples", says Heikki Kuusanmäki, Postdoctoral Researcher who led the laboratory experiments of the study at the Institute for Molecular Medicine Finland FIMM, University of Helsinki.
The majority (88%) of the patients tested with this method who were presumed sensitive to venetoclax also benefited from the actual drug treatment.
According to Dr. Kontro, the study is a great example of national collaboration. The study involved 39 AML patients from all over Finland, and all university hospitals were also actively involved in its implementation.
“One of our key objectives was to make this combination therapy available to Finnish leukemia patients. National reimbursement for it was granted in December", says Mika Kontro.
The study will continue and has expanded to include 104 patients. A joint Nordic multi-centre/multi-laboratory clinical trial is currently underway to determine the reproducibility of the method when performed in different laboratories.
The study has been funded by several foundations, in particular the Foundation for the Finnish Cancer Institute and university hospitals.
Kuusanmäki H, Kytölä S, Vänttinen I, Ruokoranta T, Ranta A, Huuhtanen J, Suvela M, Parsons A, Holopainen A, Partanen A, Kuusisto MEL, Koskela S, Räty R, Itälä-Remes M, Västrik I, Dufva O, Siitonen S, Porkka K, Wennerberg K, Heckman CA, Ettala P, Pyörälä M, Rimpiläinen J, Siitonen T, Kontro M. Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia. Haematologica. 2022 Dec 15. doi: 10.3324/haematol.2022.281692. Epub ahead of print.
Dr. Mika Kontro, Specialist in Haematology
Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki, HUS Comprehensive Cancer Center and the Foundation for the Finnish Cancer Institute
Postdoctoral Researcher Heikki Kuusanmäki
Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki and the Foundation for the Finnish Cancer Institute
Tel +358 50 325 1511