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

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.