Outcomes and genetic dynamics of acute myeloid leukemia at first relapse

• Published in: Haematologica (Roma) Vol. 109; no. 11; pp. 3543 - 3556
• Main Authors: Bataller, Alex, Kantarjian, Hagop, Bazinet, Alexandre, Kadia, Tapan, Daver, Naval, DiNardo, Courtney D., Borthakur, Gautam, Loghavi, Sanam, Patel, Keyur, Tang, Guilin, Sasaki, Koji, Short, Nicholas J., Yilmaz, Musa, Issa, Ghayas C., Alvarado, Yesid, Montalban-Bravo, Guillermo, Maiti, Abhishek, Abbas, Hussein A., Takahashi, Koichi, Pierce, Sherry, Jabbour, Elias, Garcia-Manero, Guillermo, Ravandi, Farhad
• Format: Journal Article
• Language: English
• Published: Italy Fondazione Ferrata Storti 01.11.2024; Ferrata Storti Foundation
• Subjects: Acute Myeloid Leukemia; Adolescent; Adult; Aged; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - therapy; Male; Middle Aged; Mutation; Prognosis; Recurrence; Transplantation, Homologous; Treatment Outcome; Young Adult
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2024.285057

Patients with relapsed acute myeloid leukemia (rAML) experience dismal outcomes. We performed a comprehensive analysis of patients with rAML to determine the genetic dynamics and survival predictive factors. We analyzed 875 patients with newly diagnosed AML who received intensive treatment (IT) or low-intensity treatment (LIT). Of these patients, 197 experienced subsequent rAML. Data was available for 164 patients, with a median time from CR/CRi to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation (alloSCT). At relapse mutations in genes involved in pathway signaling tended to disappear, whereas clonal hematopoiesis-related mutations or TP53 tended to persist. Patients with normal karyotypes tended to acquire cytogenetic abnormalities at relapse. Patients treated with IT had a higher emergence rate of TP53 mutations (16%), compared to patients treated with LIT (1%, P = 0.009). The overall response rates were 38% and 35% for patients treated with salvage IT or LIT, respectively. Seventeen patients (10%) underwent alloSCT after salvage therapy. The median overall survival (OS) duration after relapse was 5.3 months, with a 1-year OS rate of 17.6%. Complex karyotype (hazard ratio [HR] = 2.14, P < 0.001), a KMT2A rearrangement (HR = 3.52, P = 0.011), time in remission < 12 months (HR = 1.71, P = 0.011), and an elevated white blood cell count at relapse (HR = 2.38, P = 0.005) were independent risk factors for OS duration. More effective frontline and maintenance therapies are warranted to prevent rAML.