Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia. / Kuusanmäki, Heikki; Kytölä, Sari; Vänttinen, Ida; Ruokoranta, Tanja; Ranta, Amanda; Huuhtanen, Jani; Suvela, Minna; Parsons, Alun; Holopainen, Annasofia; Partanen, Anu; Kuusisto, Milla E.L.; Koskela, Sirpa; Räty, Riikka; Itälä-Remes, Maija; Västrik, Imre; Dufva, Olli; Siitonen, Sanna; Porkka, Kimmo; Wennerberg, Krister; Heckman, Caroline A.; Ettala, Pia; Pyörälä, Marja; Rimpiläinen, Johanna; Siitonen, Timo; Kontro, Mika.

In: Haematologica, Vol. 108, No. 7, 2023, p. 1768-1781.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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 2023, 'Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia', Haematologica, vol. 108, no. 7, pp. 1768-1781. https://doi.org/10.3324/haematol.2022.281692

APA

Kuusanmäki, H., Kytölä, S., Vänttinen, I., Ruokoranta, T., Ranta, A., Huuhtanen, J., Suvela, M., Parsons, A., Holopainen, A., Partanen, A., Kuusisto, M. E. L., Koskela, S., Räty, R., Itälä-Remes, M., Västrik, I., Dufva, O., Siitonen, S., Porkka, K., Wennerberg, K., ... Kontro, M. (2023). Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia. Haematologica, 108(7), 1768-1781. https://doi.org/10.3324/haematol.2022.281692

Vancouver

Kuusanmäki H, Kytölä S, Vänttinen I, Ruokoranta T, Ranta A, Huuhtanen J et al. Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia. Haematologica. 2023;108(7):1768-1781. https://doi.org/10.3324/haematol.2022.281692

Author

Kuusanmäki, Heikki ; Kytölä, Sari ; Vänttinen, Ida ; Ruokoranta, Tanja ; Ranta, Amanda ; Huuhtanen, Jani ; Suvela, Minna ; Parsons, Alun ; Holopainen, Annasofia ; Partanen, Anu ; Kuusisto, Milla E.L. ; Koskela, Sirpa ; Räty, Riikka ; Itälä-Remes, Maija ; Västrik, Imre ; Dufva, Olli ; Siitonen, Sanna ; Porkka, Kimmo ; Wennerberg, Krister ; Heckman, Caroline A. ; Ettala, Pia ; Pyörälä, Marja ; Rimpiläinen, Johanna ; Siitonen, Timo ; Kontro, Mika. / Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia. In: Haematologica. 2023 ; Vol. 108, No. 7. pp. 1768-1781.

Bibtex

@article{ad948926a849476b8635e710118daea9,

title = "Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia",

abstract = "The BCL-2 inhibitor venetoclax has revolutionized the treatment of acute myeloid leukemia (AML) in patients not benefiting from intensive chemotherapy. Nevertheless, treatment failure remains a challenge, and predictive markers are needed, particularly for relapsed or refractory AML. Ex vivo drug sensitivity testing may correlate with outcomes, but its prospective predictive value remains unexplored. Here we report the results of the first stage of the prospective phase II VenEx trial evaluating the utility and predictiveness of venetoclax sensitivity testing using different cell culture conditions and cell viability assays in patients receiving venetoclax-azacitidine. Participants with de novo AML ineligible for intensive chemotherapy, relapsed or refractory AML, or secondary AML were included. The primary endpoint was the treatment response in participants showing ex vivo sensitivity and the key secondary endpoints were the correlation of sensitivity with responses and survival. Venetoclax sensitivity testing was successful in 38/39 participants. Experimental conditions significantly influenced the predictive accuracy. Blast-specific venetoclax sensitivity measured in conditioned medium most accurately correlated with treatment outcomes; 88% of sensitive participants achieved a treatment response. The median survival was significantly longer for participants who were ex vivo-sensitive to venetoclax (14.6 months for venetoclax-sensitive patients vs. 3.5 for venetoclax-insensitive patients, P<0.001). This analysis illustrates the feasibility of integrating drug-response profiling into clinical practice and demonstrates excellent predictivity.",

author = "Heikki Kuusanm{\"a}ki and Sari Kyt{\"o}l{\"a} and Ida V{\"a}nttinen and Tanja Ruokoranta and Amanda Ranta and Jani Huuhtanen and Minna Suvela and Alun Parsons and Annasofia Holopainen and Anu Partanen and Kuusisto, {Milla E.L.} and Sirpa Koskela and Riikka R{\"a}ty and Maija It{\"a}l{\"a}-Remes and Imre V{\"a}strik and Olli Dufva and Sanna Siitonen and Kimmo Porkka and Krister Wennerberg and Heckman, {Caroline A.} and Pia Ettala and Marja Py{\"o}r{\"a}l{\"a} and Johanna Rimpil{\"a}inen and Timo Siitonen and Mika Kontro",

year = "2023",

doi = "10.3324/haematol.2022.281692",

language = "English",

volume = "108",

pages = "1768--1781",

journal = "Haematologica",

issn = "0390-6078",

publisher = "Ferrata Storti Foundation",

number = "7",

}

RIS

TY - JOUR

T1 - Ex vivo venetoclax sensitivity testing predicts treatment response in acute myeloid leukemia

AU - Kuusanmäki, Heikki

AU - Kytölä, Sari

AU - Vänttinen, Ida

AU - Ruokoranta, Tanja

AU - Ranta, Amanda

AU - Huuhtanen, Jani

AU - Suvela, Minna

AU - Parsons, Alun

AU - Holopainen, Annasofia

AU - Partanen, Anu

AU - Kuusisto, Milla E.L.

AU - Koskela, Sirpa

AU - Räty, Riikka

AU - Itälä-Remes, Maija

AU - Västrik, Imre

AU - Dufva, Olli

AU - Siitonen, Sanna

AU - Porkka, Kimmo

AU - Wennerberg, Krister

AU - Heckman, Caroline A.

AU - Ettala, Pia

AU - Pyörälä, Marja

AU - Rimpiläinen, Johanna

AU - Siitonen, Timo

AU - Kontro, Mika

PY - 2023

Y1 - 2023

N2 - The BCL-2 inhibitor venetoclax has revolutionized the treatment of acute myeloid leukemia (AML) in patients not benefiting from intensive chemotherapy. Nevertheless, treatment failure remains a challenge, and predictive markers are needed, particularly for relapsed or refractory AML. Ex vivo drug sensitivity testing may correlate with outcomes, but its prospective predictive value remains unexplored. Here we report the results of the first stage of the prospective phase II VenEx trial evaluating the utility and predictiveness of venetoclax sensitivity testing using different cell culture conditions and cell viability assays in patients receiving venetoclax-azacitidine. Participants with de novo AML ineligible for intensive chemotherapy, relapsed or refractory AML, or secondary AML were included. The primary endpoint was the treatment response in participants showing ex vivo sensitivity and the key secondary endpoints were the correlation of sensitivity with responses and survival. Venetoclax sensitivity testing was successful in 38/39 participants. Experimental conditions significantly influenced the predictive accuracy. Blast-specific venetoclax sensitivity measured in conditioned medium most accurately correlated with treatment outcomes; 88% of sensitive participants achieved a treatment response. The median survival was significantly longer for participants who were ex vivo-sensitive to venetoclax (14.6 months for venetoclax-sensitive patients vs. 3.5 for venetoclax-insensitive patients, P<0.001). This analysis illustrates the feasibility of integrating drug-response profiling into clinical practice and demonstrates excellent predictivity.

AB - The BCL-2 inhibitor venetoclax has revolutionized the treatment of acute myeloid leukemia (AML) in patients not benefiting from intensive chemotherapy. Nevertheless, treatment failure remains a challenge, and predictive markers are needed, particularly for relapsed or refractory AML. Ex vivo drug sensitivity testing may correlate with outcomes, but its prospective predictive value remains unexplored. Here we report the results of the first stage of the prospective phase II VenEx trial evaluating the utility and predictiveness of venetoclax sensitivity testing using different cell culture conditions and cell viability assays in patients receiving venetoclax-azacitidine. Participants with de novo AML ineligible for intensive chemotherapy, relapsed or refractory AML, or secondary AML were included. The primary endpoint was the treatment response in participants showing ex vivo sensitivity and the key secondary endpoints were the correlation of sensitivity with responses and survival. Venetoclax sensitivity testing was successful in 38/39 participants. Experimental conditions significantly influenced the predictive accuracy. Blast-specific venetoclax sensitivity measured in conditioned medium most accurately correlated with treatment outcomes; 88% of sensitive participants achieved a treatment response. The median survival was significantly longer for participants who were ex vivo-sensitive to venetoclax (14.6 months for venetoclax-sensitive patients vs. 3.5 for venetoclax-insensitive patients, P<0.001). This analysis illustrates the feasibility of integrating drug-response profiling into clinical practice and demonstrates excellent predictivity.

U2 - 10.3324/haematol.2022.281692

DO - 10.3324/haematol.2022.281692

M3 - Journal article

C2 - 36519325

AN - SCOPUS:85164232369

VL - 108

SP - 1768

EP - 1781

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 7

ER -

ID: 360404017

Biotech Research & Innovation Centre