Clinical outcomes associated with <i>NPM1</i> mutations in patients with relapsed or refractory AML
Ghayas C. Issa, Aram Bidikian, Sangeetha Venugopal, Marina Konopleva, Courtney D. DiNardo, Tapan M. Kadia, Gautam Borthakur, Elias Jabbour, Naveen Pemmaraju, Musa Yılmaz, Nicholas J. Short, Abhishek Maiti, Koji Sasaki, Lucia Masárová, Sherry Pierce, Koichi Takahashi, Guilin Tang, Sanam Loghavi, Keyur P. Patel, Michael Andreeff, Kapil N. Bhalla, Guillermo Garcia‐Manero, Farhad Ravandi, Hagop M. Kantarjian, Naval Daver
Abstract
Mutations in Nucleophosmin 1 (NPM1) are associated with a favorable prognosis in newly diagnosed acute myeloid leukemia (AML), however, their prognostic impact in relapsed/refractory (R/R) settings are unknown. In a retrospective analysis, we identified 206 patients (12%) with mutated NPM1 (NPM1c) and compared their outcomes to 1516 patients (88%) with NPM1 wild-type (NPM1wt). NPM1c was associated with higher rates of complete remission or complete remission with incomplete count recovery compared with NPM1wt following each line of salvage therapy (first salvage, 56% vs 37%; P < .0001; second salvage, 33% vs 22%; P = .02; third salvage, 24% vs 14%; P = .02). However, NPM1 mutations had no impact on relapse-free survival (RFS) and overall survival (OS) with each salvage therapy with a median OS following salvage 1, 2 or 3 therapies in NPM1c vs NPM1wt of 7.8 vs 6.0; 5.3 vs 4.1; and 3.5 vs 3.6 months, respectively. Notably, the addition of venetoclax to salvage regimens in patients with NPM1c improved RFS and OS (median RFS, 15.8 vs 4.6 months; P = .05; median OS, 14.7 vs 5.9 months; P = .02). In conclusion, NPM1 mutational status has a minimal impact on prognosis in relapsed or refractory AML; therefore, novel treatment strategies are required to improve outcomes in this entity.