Risk Prognostication After Hypomethylating Agents Combined With Venetoclax in AML: The PRISM Risk Model.

Authors

Curtis A Lachowiez, Joshua F Zeidner, Jad Othman, Andy Kaempf, Seongseok Yun, Maël Heiblig, Michael Heuser, Rabia Shahswar, Rafael Madero Marroquin, Joseph M Cannova, Andrius Žučenka, Jennifer Marvin-Peek, Jayastu Senapati, Yasmin Abaza, Alok Swaroop, Irene Zacheo, Federica Monaco, Amine Belhabri, Urbain Tauveron-Jalenques, Emmanuelle Tavernier, Martin Carré, Gaspar Aspas Requena, Rachel J Cook, Elie Traer, Jennifer N Saultz, Jenny O'Nions, Faisal Basheer, John Laurie, Shivani Handa, Eytan M Stein, Maria R Baer, Rebecca Olin, William Blum, Gary Schiller, Tara Lin, Emily Curran, Ashley Yocum, Ellen Madarang, Naval Daver, Tapan M Kadia, Giovanni Marconi, Yazan Madanat, Richard Dillon, Courtney D DiNardo, Ronan Swords, Juan E Arango Ossa, Justin Watts, Sanam Loghavi, Daniel A Pollyea, Elsa Bernard, PRISM-AML Investigators

Published in

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Pages JCO2600347. Jul 02, 2026. Epub Jul 02, 2026.

Abstract

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.
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).
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 < .001). Compared with the 4-gene classifier, PRISM-3 reassigned approximately 40% of patients (and >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).
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 is publicly available at prism-aml.com.

PMID:
42391582
Bibliographic data and abstract were imported from PubMed on 03 Jul 2026.

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