Venetoclax combination therapies found effective against challenging subtypes of acute myeloid leukemia
ATLANTA - Combination therapies including venetoclax and another therapy have displayed promising results against subtypes of acute myeloid leukemia (AML) that are particularly difficult to treat, including relapsed or refractory AML with a specific mutation, high-risk AML and treated secondary AML. Researchers from The University of Texas MD Anderson Cancer Center presented numerous studies involving venetoclax combination therapy for AML at the 2021 American Society of Hematology (ASH) Annual Meeting.
AML is a type of leukemia in which the myeloid stem cells produce immature blood cells, rather than mature, healthy cells, causing anemia and risk of bleeding and infection. Most patients with AML are not cured by standard-of-care treatments, and researchers are working to fill the unmet need for new, more effective therapies.
Relapsed/refractory (R/R) FLT3-mutated (FLT3+) AML is typically resistant to venetoclax, and response durations are short when treated with single agent FLT3 inhibitors. A multicenter study presented by Naval Daver, M.D., associate professor of Leukemia, included 54 patients with R/R FLT3+ AML who were treated with a combination of venetoclax and the FLT3 tyrosine kinase inhibitor, gilteritinib. The combination therapy was safe and well-tolerated, other than frequent but manageable cytopenia that occurred in 80% of the trial participants, and it produced an encouraging composite complete response rate in 74.5% of the FLT3+ patients. Additionally, the therapy cleared the FLT mutation in more than half (56.7%) of patients who responded to treatment, which may contribute to longer survival.
The study was funded by Astellas Pharma, AbbVie and Genentech. Daver has received research support and served in a consulting or advisory role for Astellas Pharma, AbbVie and Genentech. A complete list of collaborating authors and their disclosures can be found within the abstract here.
"The high complete response rate for newly diagnosed patients, especially high-risk patients such as those with TP53 mutations, is especially encouraging," Daver said. "Adding magrolimab to the existing venetoclax and azacitidine combination will be evaluated in a randomized multinational Phase III study in older/unfit patients with newly diagnosed AML."
The study was funded by Gilead and Genentech. Daver has received research support and served in a consulting or advisory role for Genentech. A complete list of collaborating authors and their disclosures can be found within the abstract here.
Retrospective analysis of frontline treatment approach with treated secondary AML (Abstract 794)
"The response rates associated with HMA and venetoclax therapy imply that this combination therapy may be preferable to the typical chemotherapy-based approaches in treated secondary AML," Venugopal said. "However, the prognosis for treated secondary AML is poor, and effective treatment options for this high-risk patient subset is an urgent unmet need."
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