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Ex Vivo Venetoclax Sensitivity Predicts Clinical Response in Acute Myeloid Leukemia in the Prospective VenEx Trial
Tekijät: Kytölä, 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
Kustantaja: American Society of Hematology
Julkaisuvuosi: 2025
Journal: Blood
Tietokannassa oleva lehden nimi: Blood Journal
Lehden akronyymi: Blood
Vuosikerta: 145
Numero: 4
Aloitussivu: 409
Lopetussivu: 421
ISSN: 0006-4971
eISSN: 1528-0020
DOI: https://doi.org/10.1182/blood.2024024968
Verkko-osoite: https://doi.org/10.1182/blood.2024024968
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.
