Treatment patterns and outcomes in secondary acute myeloid leukemia arising after hypomethylating agents: PETHEMA registry study

Abstract 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.