Venetoclax-based therapy versus hypomethylating agents alone in unfit patients with newly diagnosed acute myeloid leukemia: a real-world study from the PETHEMA registry.

Authors

Gaspar Aspas Requena, Eliana Aguiar, Joana Brioso, Rosa Ayala, Josefina Serrano López, Jorge Labrador Gómez, Eduardo Rodríguez-Arbolí, Mar Tormo, Teresa Bernal Del Castillo, Olga Arce Fernández, Francisco Ibáñez Alís, Manuel Pérez Encinas, Carlos Rodríguez-Medina, Ágata Almela Gallego, Olga Salamero, José Luis López Lorenzo, Claudia Lucía Sossa Melo, María José Mela Osorio, Juan Miguel Bergua Burgues, Susana Vives, Aitor Abuín, María Dolores Madrigal, Cristina Gil, Alberto Giménez Conca, Marta Valero Núñez, José Mário Mariz, María-Ángeles Foncillas, Silvina Palmer, Marcela Espinoza, Bernardo Javier González González, María Carmen García Garay, Lara María Gómez García, Daniel García Belmonte, Ana Alfonso Piérola, Diana Marcela Cuervo Lozada, Carlos Varón, Ana Lisa Basquiera, Miguel López, María Lourdes Amador Barciela, María Solé Rodríguez, María Marta Rivas, Sandra Casal Marini, Alicia Roldán Pérez, María-Belén Vidriales, Raimundo García Boyero, Isabel Recio, María Luz Amigo, Kenny Gálvez, Pilar Lloret Madrid, Pau Montesinos

Published in

Leukemia. Oct 06, 2026. Epub Oct 06, 2026.

Abstract

Real-world comparisons of venetoclax (VEN)-based versus hypomethylating agent (HMA) monotherapy in unfit, newly diagnosed AML remain limited by short follow-up, low genomic testing, and inadequate statistical power. We conducted the largest comparative analysis to date from the PETHEMA registry, including 2610 patients (929 VEN-based, 1681 HMA). Composite complete remission was higher with VEN-based therapy (64.4% vs 20.0%; P < 0.001), and both 30-day (4.8% vs 7.5%; P = 0.011) and 60-day mortality (9.7% vs 15.7%; P < 0.001) were significantly lower. Median overall survival was 11.4 versus 8.2 months (HR, 0.66; 95% CI, 0.60-0.73; P < 0.001), consistent with that of VIALE-A (HR, 0.66) despite a broader cohort (ECOG 3-4, 4.7%; secondary AML, 42.5%; adverse-risk cytogenetics, 36.5%). The benefit was confirmed by propensity score matching (HR, 0.66), era-restricted analysis (HR, 0.71), and multivariable Cox regression. A molecular gradient of benefit emerged-greatest in IDH2 (HR, 0.43), NPM1 (0.46), FLT3-ITD (0.48), IDH1 (0.55), and favorable-risk cytogenetics (0.25). In TP53-mutated AML, OS improved significantly (HR, 0.70) but remained dismal (7.0 vs 3.7 months); no benefit was observed in AML arising from antecedent MDS or MPN. These findings confirm and extend VIALE-A, refining patient selection for VEN-based therapy in routine practice.

PMID:
42839073
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.

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