RUNX1 MUTATIONS IN NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA DO NOT ADVERSELY IMPACT CLINICAL OUTCOMES IN THE MODERN ERA
Author(s): ,
Sangeetha Venugopal
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Sanam Loghavi
Affiliations:
Hematopathology,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Courtney DiNardo
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Marina Konopleva
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Tapan Kadia
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Kapil Bhalla
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Ghayas.C. Issa
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Farhad Ravandi
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Naval Daver
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Gautam Borthakur
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Elias. J. Jabbour
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Guillermo Montalban-Bravo
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Musa Yilmaz
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Kelly.S. Chien
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Abhishek Maiti
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
,
Hagop Kantarjian
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
Nicholas. J. Short
Affiliations:
Leukemia,The University of Texas, MD Anderson Cancer Center,Houston,United States
EHA Library. Venugopal S. 06/09/21; 324540; S132
Sangeetha Venugopal
Sangeetha Venugopal
Contributions
Abstract
Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S132

Type: Oral Presentation

Session title: AML classification

Background
European LeukemiaNet 2017 risk stratification classifies mutated RUNX1 (mRUNX1) as an adverse risk factor in newly diagnosed (ND) acute myeloid leukemia (AML). However, outcomes of mRUNX1 in ND AML in the current era, including with venetoclax (Ven)-based therapies, are not well defined.

Aims
We characterize the impact of RUNX1 mutations and variant allelic frequency (VAF) on outcomes of patients with ND AML across contemporary treatment regimens.

Methods
We conducted a retrospective analysis of patients (pts) with ND AML treated at our institution from 11/2009 to 7/2020. Pt were divided into AML with mRUNX1 and wild type RUNX1 (wtRUNX1); only those with presumed somatic variants based on previous annotation in literature and publicly available databases were included in the mRUNX1 group. Treatment was classified as intensive chemotherapy (IC) or low intensity chemotherapy including hypomethylating agents (LIC) with and without Ven. Response was defined as achievement of CR or CRi.

Results

Among 907 pts with ND AML, 137 (15%) had AML with mRUNX1. The median RUNX1 VAF was 33% (range, 1-96%); 29 pts (21%) had ≥2 RUNX1 mutations. Pts with mRUNX1 AML were older (median age: 71 vs. 66 years; P<0.001), more likely to have secondary AML (20% vs.13%; P=0.03), and less likely to have adverse-risk cytogenetics (20% vs. 34%; P=0.001) compared to pts with wtRUNX1. AML with mRUNX1 was more likely to have a co-mutation of SRSF2 (40% vs. 12%; P<0.001), ASXL1 (24% vs. 9%; P<0.0001), and IDH1/2 (38% vs. 25%; P=0.002), and less likely to have co-mutated TP53 (5% vs. 25%; P<0.0001).


Frontline therapies received were IC in 35 pts (26%), LIC without Ven in 66 pts (48%) and LIC with Ven in 36 pts (26%). Response rates were similar between pts with mRUNX1 and wtRUNX1 AML across therapies (IC, 77% vs. 80%; LIC without Ven, 44% vs. 52%; LIC with Ven, 72% vs. 73%). Among pts with mRUNX1 AML treated with LIC, response rates were significantly higher in those who received Ven (72% vs. 44%, P=0.007). The benefit of adding Ven to LIC was similar among pts with RUNX1 VAF <30% (response rate: 82% with Ven vs. 46% without Ven; P<0.05) and VAF ≥30% (68% vs. 43%, respectively; P<0.05). Among pts who received IC, response rates were higher in AML with mRUNX1 VAF <30% than ≥30% (100% vs. 69%; P=0.06).


Overall survival (OS) was similar in mRUNX1 and wtRUNX1 AML in both pts <60 years (P=0.8) and ≥60 years (P=0.8). RUNX1 mutation status also did not impact OS in those treated with IC (P=0.7) or LIC without Ven (P=0.8); however, among pts who received LIC with Ven, there was a strong trend towards superior OS for pts with mRUNX1 AML compared to wtRUNX1 AML (median 25.1 months [m] vs. 11.3 m; P=0.12). Pts with mRUNX1 AML who received LIC with Ven had superior OS compared to those who received LIC without Ven (median OS 25.1 m vs. 14.9 m; P=0.02).


Among those with mRUNX1 AML who received IC, OS was higher for those with VAF <30% vs. ≥30% (median OS not reached vs. 18.3 m; P=0.10). Among those with mRUNX1 VAF <30%, the addition of Ven to LIC significantly improved OS compared to LIC without Ven (median OS 25.4 m vs. 14.9 m; 2-year OS 81% vs. 12%; P=0.02); in contrast, the benefit of adding Ven to LIC in pts with mRUNX1 VAF ≥30% was less pronounced (median OS 16.4 m vs. 15.3 m; 2-year OS 43% vs. 26%; P=0.2).


 


 

Conclusion
The comparable outcomes between pts with mRUNX1 and wtRUNX1 AML question the inclusion of RUNX1 mutations as an adverse risk group. With Ven-based regimens, a median OS >2 years was observed in pts with mRUNX1 AML.

Keyword(s): AML, Prognosis, RUNX1

Presentation during EHA2021: All Oral presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: S132

Type: Oral Presentation

Session title: AML classification

Background
European LeukemiaNet 2017 risk stratification classifies mutated RUNX1 (mRUNX1) as an adverse risk factor in newly diagnosed (ND) acute myeloid leukemia (AML). However, outcomes of mRUNX1 in ND AML in the current era, including with venetoclax (Ven)-based therapies, are not well defined.

Aims
We characterize the impact of RUNX1 mutations and variant allelic frequency (VAF) on outcomes of patients with ND AML across contemporary treatment regimens.

Methods
We conducted a retrospective analysis of patients (pts) with ND AML treated at our institution from 11/2009 to 7/2020. Pt were divided into AML with mRUNX1 and wild type RUNX1 (wtRUNX1); only those with presumed somatic variants based on previous annotation in literature and publicly available databases were included in the mRUNX1 group. Treatment was classified as intensive chemotherapy (IC) or low intensity chemotherapy including hypomethylating agents (LIC) with and without Ven. Response was defined as achievement of CR or CRi.

Results

Among 907 pts with ND AML, 137 (15%) had AML with mRUNX1. The median RUNX1 VAF was 33% (range, 1-96%); 29 pts (21%) had ≥2 RUNX1 mutations. Pts with mRUNX1 AML were older (median age: 71 vs. 66 years; P<0.001), more likely to have secondary AML (20% vs.13%; P=0.03), and less likely to have adverse-risk cytogenetics (20% vs. 34%; P=0.001) compared to pts with wtRUNX1. AML with mRUNX1 was more likely to have a co-mutation of SRSF2 (40% vs. 12%; P<0.001), ASXL1 (24% vs. 9%; P<0.0001), and IDH1/2 (38% vs. 25%; P=0.002), and less likely to have co-mutated TP53 (5% vs. 25%; P<0.0001).


Frontline therapies received were IC in 35 pts (26%), LIC without Ven in 66 pts (48%) and LIC with Ven in 36 pts (26%). Response rates were similar between pts with mRUNX1 and wtRUNX1 AML across therapies (IC, 77% vs. 80%; LIC without Ven, 44% vs. 52%; LIC with Ven, 72% vs. 73%). Among pts with mRUNX1 AML treated with LIC, response rates were significantly higher in those who received Ven (72% vs. 44%, P=0.007). The benefit of adding Ven to LIC was similar among pts with RUNX1 VAF <30% (response rate: 82% with Ven vs. 46% without Ven; P<0.05) and VAF ≥30% (68% vs. 43%, respectively; P<0.05). Among pts who received IC, response rates were higher in AML with mRUNX1 VAF <30% than ≥30% (100% vs. 69%; P=0.06).


Overall survival (OS) was similar in mRUNX1 and wtRUNX1 AML in both pts <60 years (P=0.8) and ≥60 years (P=0.8). RUNX1 mutation status also did not impact OS in those treated with IC (P=0.7) or LIC without Ven (P=0.8); however, among pts who received LIC with Ven, there was a strong trend towards superior OS for pts with mRUNX1 AML compared to wtRUNX1 AML (median 25.1 months [m] vs. 11.3 m; P=0.12). Pts with mRUNX1 AML who received LIC with Ven had superior OS compared to those who received LIC without Ven (median OS 25.1 m vs. 14.9 m; P=0.02).


Among those with mRUNX1 AML who received IC, OS was higher for those with VAF <30% vs. ≥30% (median OS not reached vs. 18.3 m; P=0.10). Among those with mRUNX1 VAF <30%, the addition of Ven to LIC significantly improved OS compared to LIC without Ven (median OS 25.4 m vs. 14.9 m; 2-year OS 81% vs. 12%; P=0.02); in contrast, the benefit of adding Ven to LIC in pts with mRUNX1 VAF ≥30% was less pronounced (median OS 16.4 m vs. 15.3 m; 2-year OS 43% vs. 26%; P=0.2).


 


 

Conclusion
The comparable outcomes between pts with mRUNX1 and wtRUNX1 AML question the inclusion of RUNX1 mutations as an adverse risk group. With Ven-based regimens, a median OS >2 years was observed in pts with mRUNX1 AML.

Keyword(s): AML, Prognosis, RUNX1

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies