Treatment patterns and outcomes in secondary acute myeloid leukemia arising after hypomethylating agents: PETHEMA registry study
Lloret-Madrid P, Boluda B, Martínez-López J, Bergua J, Rodriguez Arboli E, Labrador J, Sossa C, Gil C, Algarra L, Lavilla-Rubira E, Serrano J, de Rueda B, Ibañez F, González González BJ, Amigo ML, García Belmonte D, Rodríguez-Medina C, Gómez-Roncero MI, Colorado M, López Lorenzo JL, Tormo M, Arce Fernández O, Cano-Ferri I, Solana-Altabella A, Foncillas MA, Alfonso Pierola A, Vives S, Núñez MV, López-Vidal H, Pérez-Santaolalla E, Hermosín Ramos L, García Boyero R, Llorente González L, Roldán A, Calderón SC, Infante JB, Olave T, García-Suárez J, de Laiglesia A, Rodríguez-Veiga R, Trigo F, Martínez-Cuadrón D, Montesinos P.
CANCER-AM CANCER SOC
Background: Patients with secondary acute myeloid leukemia who previously received hypomethylating agents for prior myeloid neoplasms (HMA-sAML) face a dismal prognosis.
Methods: The authors analyze the characteristics, therapeutic approaches, and outcomes of patients with HMA-sAML from the Programa Español para el Tratamiento de Hemopatías Malignas (PETHEMA) registry.
Results: A total of 479 patients were included, mostly from prior myelodysplastic syndrome (84%). Frontline therapy consisted of intensive chemotherapy (IC) in 31%, low-dose cytarabine-based in 19%, supportive care and clinical trial 17% each, and HMA-based therapy in 12% and 4% in venetoclax-based regimen. Complete remission was achieved in 95 patients (27%), with higher rate among IC and venetoclax-based groups (44% and 41%, respectively). The median overall survival (OS) was 4.93 months, with 7.68 months for IC patients, 7.82 months after HMA monotherapy, and 4.66 months after venetoclax-based regimens. Patients who underwent allogeneic hematopoietic stem cell transplantation in first remission (n = 33, 9%) had a better survival outcome (median OS not reached). Multivariate analyses identified age (≥65 years), Eastern Cooperative Oncology Group >2, higher white blood cell count, and adverse risk cytogenetic as adverse prognostic factors, whereas NPM1 mutation was a favorable factor.
Conclusions: Patients with HMA-sAML have a poor prognosis and suboptimal outcomes with conventional treatments, including BCL2 inhibitors, highlighting the need for clinical trials targeting this population.
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