TY - JOUR
T1 - A novel prognostic risk model for patients with refractory/relapsed acute myeloid leukemia receiving venetoclax plus hypomethylating agents
T2 - ACUTE MYELOID LEUKEMIA
AU - Shahswar, Rabia
AU - Gabdoulline, Razif
AU - Krueger, Katja
AU - Wichmann, Martin
AU - Götze, Katharina S.
AU - Braitsch, Krischan
AU - Meggendorfer, Manja
AU - Schmalbrock, Laura
AU - Bullinger, Lars
AU - Modemann, Franziska
AU - Fiedler, Walter
AU - Krauter, Juergen
AU - Kaun, Stephan
AU - Rotermund, Susanne
AU - Voß, Andreas
AU - Behrens, Yvonne Lisa
AU - Bergmann, Anke Katharina
AU - Koller, Elisabeth
AU - Beutel, Gernot
AU - Thol, Felicitas
AU - Heidel, Florian
AU - Heuser, Michael
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025
Y1 - 2025
N2 - Off-label hypomethylating agents and venetoclax (HMA/VEN) are often used for relapsed and refractory (R/R) AML patients. However, predictors of outcome are elusive. The objective of the current retrospective observational multicenter study of 240 adult patients (median age 68.6 years) with R/R AML was to establish a prognostic risk score. Overall response was documented in 106 (44%) patients. With a median follow-up of 31.5 months, 179 deaths were recorded. Median overall survival (mOS) was 7.9 months. In multivariate analysis of the subgroup with molecular information (n = 174), risk factors for inferior survival included the presence of extramedullary disease, HMA pretreatment and mutations in NF1, PTPN11, FLT3, and TP53, whereas mutated SF3B1 was identified as favorable risk factor. These risk factors were subsequently applied to construct an HR-weighted risk model that allocated patients to one of three risk groups with significantly different survival outcomes: favorable (n = 46; mOS 21.4 months), intermediate (n = 75; mOS 7.5 months), and adverse (n = 53; mOS 4.6 months; p < 0.001). The model was validated in 189 AML patients treated with HMA/VEN in first line. This clinical-molecular, 3-tiered venetoclax prognostic risk score (VEN-PRS) for HMA/VEN treatment outcomes in R/R AML patients will support the selection of appropriate treatment options in this high-risk population. (Figure presented.)
AB - Off-label hypomethylating agents and venetoclax (HMA/VEN) are often used for relapsed and refractory (R/R) AML patients. However, predictors of outcome are elusive. The objective of the current retrospective observational multicenter study of 240 adult patients (median age 68.6 years) with R/R AML was to establish a prognostic risk score. Overall response was documented in 106 (44%) patients. With a median follow-up of 31.5 months, 179 deaths were recorded. Median overall survival (mOS) was 7.9 months. In multivariate analysis of the subgroup with molecular information (n = 174), risk factors for inferior survival included the presence of extramedullary disease, HMA pretreatment and mutations in NF1, PTPN11, FLT3, and TP53, whereas mutated SF3B1 was identified as favorable risk factor. These risk factors were subsequently applied to construct an HR-weighted risk model that allocated patients to one of three risk groups with significantly different survival outcomes: favorable (n = 46; mOS 21.4 months), intermediate (n = 75; mOS 7.5 months), and adverse (n = 53; mOS 4.6 months; p < 0.001). The model was validated in 189 AML patients treated with HMA/VEN in first line. This clinical-molecular, 3-tiered venetoclax prognostic risk score (VEN-PRS) for HMA/VEN treatment outcomes in R/R AML patients will support the selection of appropriate treatment options in this high-risk population. (Figure presented.)
UR - http://www.scopus.com/inward/record.url?scp=85217157763&partnerID=8YFLogxK
U2 - 10.1038/s41375-024-02501-6
DO - 10.1038/s41375-024-02501-6
M3 - Article
C2 - 39779979
AN - SCOPUS:85217157763
SN - 0887-6924
JO - Leukemia
JF - Leukemia
ER -
