Risk Prognostication After Hypomethylating Agents Combined With Venetoclax in AML: The PRISM Risk Model
Menée à partir de données internationales portant sur 1 918 patients atteints d'une leucémie myéloïde aiguë traitée par agents hypométhylants en combinaison avec le vénétoclax puis validée auprès de 722 personnes supplémentaires, cette étude évalue l'association entre le score du modèle PRISM, basé sur 17 variables cliniques et génomiques, et la survie globale des patients puis compare la performance de ce modèle par rapport au classificateur à 4 gènes (basé sur la présence de mutations au niveau des gènes FLT3-ITD, N/KRAS et TP53)
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 < .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).
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 is publicly available at prism-aml.com.
Journal of Clinical Oncology , article en libre accès, 2026