TY - JOUR
T1 - Differential prognostic impact of RUNX1 mutations according to frontline therapy in patients with acute myeloid leukemia
AU - Venugopal, Sangeetha
AU - DiNardo, Courtney D.
AU - Loghavi, Sanam
AU - Qiao, Wei
AU - Ravandi, Farhad
AU - Konopleva, Marina
AU - Kadia, Tapan
AU - Bhalla, Kapil
AU - Jabbour, Elias
AU - Issa, Ghayas C.
AU - Macaron, Walid
AU - Daver, Naval
AU - Borthakur, Gautam
AU - Montalban-Bravo, Guillermo
AU - Yilmaz, Musa
AU - Patel, Keyur P.
AU - Kanagal-Shamanna, Rashmi
AU - Chien, Kelly
AU - Maiti, Abhishek
AU - Kantarjian, Hagop
AU - Short, Nicholas J.
N1 - Publisher Copyright:
© 2022 Wiley Periodicals LLC.
PY - 2022/12
Y1 - 2022/12
N2 - RUNX1-mutated (mRUNX1) acute myeloid leukemia (AML) has historically been associated with poor outcomes in the setting of conventional chemotherapy. The prognostic impact of mRUNX1 AML is not well-established in the current era of lower-intensity treatment regimens incorporating venetoclax. We retrospectively analyzed 907 patients with newly diagnosed AML, including 137 patients with mRUNX1 AML, who underwent first-line therapy with intensive chemotherapy (IC), low-intensity therapy without venetoclax (LIT without VEN), or LIT with VEN. When stratified by RUNX1 status, there was no statistically significant difference in outcomes between mRUNX1 and wild-type (wtRUNX1) AML, regardless of therapy received. However, among patients who received LIT with VEN, there was a trend towards superior overall survival (OS) in those with mRUNX1 AML (median OS for mRUNX1 vs. wtRUNX1: 25.1 vs. 11.3 months; 2-year OS 54% vs. 33%; p = 0.12). In patients without another adverse-risk cyto-molecular feature, the presence of mRUNX1 conferred inferior OS in patients who received IC (p = 0.02) or LIT without VEN (p = 0.003) but not in those who received LIT with VEN (mRUNX1 vs. wtRUNX1: 25.1 vs. 30.0 months; 2-year OS 59% vs. 54%; p = 0.86). A multivariate analysis showed possible interaction between RUNX1 mutation status and treatment, suggesting a differential prognostic impact of RUNX1 mutations when patients received IC versus LIT with VEN. In summary, the prognostic impact of mRUNX1 AML may be treatment-dependent, and the presence of RUNX1 mutations may not impact clinical outcomes when venetoclax-based regimens are used.
AB - RUNX1-mutated (mRUNX1) acute myeloid leukemia (AML) has historically been associated with poor outcomes in the setting of conventional chemotherapy. The prognostic impact of mRUNX1 AML is not well-established in the current era of lower-intensity treatment regimens incorporating venetoclax. We retrospectively analyzed 907 patients with newly diagnosed AML, including 137 patients with mRUNX1 AML, who underwent first-line therapy with intensive chemotherapy (IC), low-intensity therapy without venetoclax (LIT without VEN), or LIT with VEN. When stratified by RUNX1 status, there was no statistically significant difference in outcomes between mRUNX1 and wild-type (wtRUNX1) AML, regardless of therapy received. However, among patients who received LIT with VEN, there was a trend towards superior overall survival (OS) in those with mRUNX1 AML (median OS for mRUNX1 vs. wtRUNX1: 25.1 vs. 11.3 months; 2-year OS 54% vs. 33%; p = 0.12). In patients without another adverse-risk cyto-molecular feature, the presence of mRUNX1 conferred inferior OS in patients who received IC (p = 0.02) or LIT without VEN (p = 0.003) but not in those who received LIT with VEN (mRUNX1 vs. wtRUNX1: 25.1 vs. 30.0 months; 2-year OS 59% vs. 54%; p = 0.86). A multivariate analysis showed possible interaction between RUNX1 mutation status and treatment, suggesting a differential prognostic impact of RUNX1 mutations when patients received IC versus LIT with VEN. In summary, the prognostic impact of mRUNX1 AML may be treatment-dependent, and the presence of RUNX1 mutations may not impact clinical outcomes when venetoclax-based regimens are used.
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U2 - 10.1002/ajh.26724
DO - 10.1002/ajh.26724
M3 - Article
C2 - 36087091
AN - SCOPUS:85139034570
SN - 0361-8609
VL - 97
SP - 1560
EP - 1567
JO - American journal of hematology
JF - American journal of hematology
IS - 12
ER -