| Authors |
Lachowiez, Curtis A ; Zeidner, Joshua F ; Othman, Jad ; Kaempf, Andy ; Yun, Seongseok ; Heiblig, Maël ; Heuser, Michael ; Shahswar, Rabia ; Madero Marroquin, Rafael ; Cannova, Joseph M ; Žučenka, Andrius ; Marvin-Peek, Jennifer ; Senapati, Jayastu ; Abaza, Yasmin ; Swaroop, Alok ; Zacheo, Irene ; Monaco, Federica ; Belhabri, Amine ; Tauveron-Jalenques, Urbain ; Tavernier, Emmanuelle ; Carré, Martin ; Aspas Requena, Gaspar ; Cook, Rachel J ; Traer, Elie ; Saultz, Jennifer N ; O'Nions, Jenny ; Basheer, Faisal ; Laurie, John ; Handa, Shivani ; Stein, Eytan M ; Baer, Maria R ; Olin, Rebecca ; Blum, William ; Schiller, Gary ; Lin, Tara ; Curran, Emily ; Yocum, Ashley ; Madarang, Ellen ; Daver, Naval ; Kadia, Tapan M ; Marconi, Giovanni ; Madanat, Yazan ; Dillon, Richard ; DiNardo, Courtney D ; Swords, Ronan ; Arango Ossa, Juan E ; Watts, Justin ; Loghavi, Sanam ; Pollyea, Daniel A ; Bernard, Elsa |
| Abstract [eng] |
PURPOSE – As risk stratification for patients with AML treated with lower-intensity venetoclax-based therapy remains suboptimal, we developed and validated a prognostic model integrating clinical, cytogenetic, and molecular features. METHODS – We assembled a multinational data set comprising 2, 092 adults with newly diagnosed AML treated with hypomethylating agents plus venetoclax (HMA + VEN). One thousand nine hundred eighteen patients with complete data were randomly divided into training (70%) and internal validation (30%) cohorts. Two independent external validation cohorts were assembled (n = 500 and n = 222). Modeling overall survival (OS), Elastic Net regression was applied in 1, 000 bootstrap samples from the training cohort to select variables for a Ridge regression, which generated a continuous Prognostic Risk Integration for Survival Modeling (PRISM) score and risk categories based on tertiles (PRISM-3: low, moderate, high). These PRISM indices were then computed for the validation cohorts and compared with the 4-gene classifier (based on mutations in FLT3-ITD, N/KRAS, and TP53). RESULTS – PRISM integrated 17 clinical and genomic variables and demonstrated a linear association with OS. PRISM-3 stratified survival consistently across all cohorts (median OS: 25.1-28.8 months for low risk, 12.5-14.7 months for moderate risk, and 5.8-6.7 months for high risk; P 50% of those with favorable risk) and demonstrated significantly better discrimination in validation cohorts (C-index 0.63-0.65 v 0.59-0.61; P < .05). CONCLUSION – PRISM is a validated prognostic model for patients with AML receiving HMA + VEN that improves survival risk stratification beyond current standard tools and supports individualized, risk-adapted clinical decision making. The model, the PRISM-AML Risk Calculator, is publicly available. |
