Outcomes and genetic dynamics of acute myeloid leukemia at first relapse
Álex Bataller, Hagop M. Kantarjian, Alexandre Bazinet, Tapan M. Kadia, Naval Daver, Courtney D. DiNardo, Gautam Borthakur, Sanam Loghavi, Keyur Patel, Guilin Tang, Koji Sasaki, Nicholas J. Short, Musa Yılmaz, Ghayas C. Issa, Yesid Alvarado, Guillermo Montalban‐Bravo, Abhishek Maiti, Hussein A. Abbas, Koichi Takahashi, Sherry Pierce, Elias Jabbour, Guillermo Garcia‐Manero, Farhad Ravandi
Abstract
Patients with relapsed acute myeloid leukemia (AML) experience dismal outcomes. We performed a comprehensive analysis of patients with relapsed AML to determine the genetic dynamics and factors predicting survival. We analyzed 875 patients with newly diagnosed AML who received intensive treatment or low-intensity treatment. Of these patients, 197 subsequently relapsed. Data were available for 164 of these patients, with a median time from complete remission/complete remission with incomplete blood count recovery to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation. 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 intensively had a higher rate of emergence of TP53 mutations (16%), compared to patients given low-intensity treatment (1%, P=0.009). The overall response rates were 38% and 35% for patients treated with salvage intensive treatment or low-intensity treatment, respectively. Seventeen patients (10%) underwent allogeneic stem cell transplantation after salvage therapy. The median overall survival duration after relapse was 5.3 months, with a 1-year overall survival 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 overall survival duration. More effective frontline and maintenance therapies are warranted to prevent relapsed AML.