TY - JOUR
T1 - Clinical outcomes associated with NPM1 mutations in patients with relapsed or refractory AML
AU - Issa, Ghayas C.
AU - Bidikian, Aram
AU - Venugopal, Sangeetha
AU - Konopleva, Marina
AU - DiNardo, Courtney D.
AU - Kadia, Tapan M.
AU - Borthakur, Gautam
AU - Jabbour, Elias
AU - Pemmaraju, Naveen
AU - Yilmaz, Musa
AU - Short, Nicholas J.
AU - Maiti, Abhishek
AU - Sasaki, Koji
AU - Masarova, Lucia
AU - Pierce, Sherry
AU - Takahashi, Koichi
AU - Tang, Guilin
AU - Loghavi, Sanam
AU - Patel, Keyur
AU - Andreeff, Michael
AU - Bhalla, Kapil
AU - Garcia-Maner, Guillermo
AU - Ravandi, Farhad
AU - Kantarjian, Hagop
AU - Daver, Naval
N1 - Publisher Copyright:
© 2023 by The American Society of Hematology.
PY - 2023/3/28
Y1 - 2023/3/28
N2 - 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.
AB - 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.
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U2 - 10.1182/bloodadvances.2022008316
DO - 10.1182/bloodadvances.2022008316
M3 - Article
C2 - 36322818
AN - SCOPUS:85146064834
SN - 2473-9529
VL - 7
SP - 933
EP - 942
JO - Blood Advances
JF - Blood Advances
IS - 6
ER -