Ex Vivo Venetoclax Sensitivity Predicts Clinical Response in Acute Myeloid Leukemia in the Prospective VenEx Trial.

Autor:	Kytölä S; Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland., Vänttinen IM; University of Helsinki, Helsinki, Finland., Ruokoranta T; Institute of Molecular Medicine Finland (FIMM), Helsinki, Finland., Partanen A; Kuopio University Hospital, Kuopio, Finland., Holopainen A; Kuopio University Hospital, Kuopio, Finland., Saad J; University of Helsinki, Helsinki, Finland., Kuusisto MEL; University of Oulu and Oulu University Hospital, Oulu, Finland, Oulu, Finland., Koskela S; Finland., Räty RK; HUS Helsinki University Central Hospital, Helsinki, Finland., Itälä-Remes M; Turku University Hospital, Turku, Finland., Västrik I; Institute of Molecular Medicine Finland (FIMM), Helsinki, Finland., Suvela M; University of Helsinki, Helsinki, Finland., Parsons AO; University of Helsinki, Helsinki, Finland., Porkka K; Helsinki University Central Hospital Comprehensive Cancer Center, Helsinki, Finland., Wennerberg K; University of Copenhagen, Copenhagen N, Denmark., Heckman CA; University of Helsinki, Helsinki, Finland., Jalkanen T; Estimates Ltd, Turku, Finland., Huttunen T; Estimates Ltd, Turku, Finland., Ettala P MD; Turku University Hospital, Turku, Finland., Rimpiläinen J; Tampere University Hospital, Tampere, Finland., Siitonen T; Oulu University Hospital, Oulu, Finland., Pyörälä M; Kuopio University Hospital, Kuopio, Finland., Kuusanmäki H; Institute of Molecular Medicine Finland (FIMM), Helsinki, Finland., Kontro M; Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Oct 02. Date of Electronic Publication: 2024 Oct 02.
DOI:	10.1182/blood.2024024968
Abstrakt:	The BCL2 inhibitor venetoclax has shown promise for treating acute myeloid leukemia (AML). However, identifying patients likely to respond remains a challenge, especially for those with relapsed/refractory (R/R) disease. We evaluated the utility of ex vivo venetoclax sensitivity testing to predict treatment responses to venetoclax-azacitidine in a prospective, multicenter, phase 2 trial conducted by the Finnish AML Group (VenEx, NCT04267081). The trial recruited 104 participants with previously untreated (n=48), R/R (n=39) or previously treated secondary AML (sAML) (n=17). The primary endpoint was complete remission or complete remission with incomplete hematologic recovery (CR/CRi) rate in ex vivo sensitive trial participants during the first three therapy cycles. The key secondary endpoints included the correlations between ex vivo drug sensitivity, responses, and survival. Venetoclax sensitivity was successfully assessed in 102/104 participants, with results available within a median of three days from sampling. In previously untreated AML, ex vivo sensitivity corresponded to an 85% (34/40) CR/CRi rate, with a median overall survival (OS) of 28.7 months, compared to 5.5 months for ex vivo resistant patients (p = 0.002). For R/R/sAML, ex vivo sensitivity resulted in a 62% CR/CRi rate (21/34) and median OS of 9.7 versus 3.3 months for ex vivo resistant patients (p < 0.001). In univariate and multivariate analysis, ex vivo venetoclax sensitivity was the strongest predictor for a favorable treatment response and survival. The VenEx trial demonstrates the feasibility of integrating ex vivo drug testing into clinical practice to identify AML patients, particularly in the R/R setting, who benefit from venetoclax. (Copyright © 2024 American Society of Hematology.)
Databáze:	MEDLINE
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