A1 Refereed original research article in a scientific journal

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




AuthorsKytölä, Sari; Vänttinen, Ida Maria; Ruokoranta, Tanja; Partanen, Anu; Holopainen, Annasofia; Saad, Joseph; Kuusisto, Milla E.L.; Koskela, Sirpa; Räty, Riikka Katariina; Itälä-Remes, Maija; Västrik, Imre; Suvela, Minna; Parsons, Alun Owen; Porkka, Kimmo; Wennerberg, Krister; Heckman, Caroline A.; Jalkanen, Tero; Huttunen, Teppo; Ettala, Pia; Rimpiläinen, Johanna; Siitonen, Timo; Pyörälä, Marja; Kuusanmäki, Heikki; Kontro, Mika

PublisherAmerican Society of Hematology

Publication year2025

JournalBlood

Journal name in sourceBlood Journal

Journal acronymBlood

Volume145

Issue4

First page 409

Last page421

ISSN0006-4971

eISSN1528-0020

DOIhttps://doi.org/10.1182/blood.2024024968(external)

Web address https://doi.org/10.1182/blood.2024024968(external)


Abstract
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.



Last updated on 2025-24-02 at 10:27