10-DAY DECITABINE AND VENETOCLAX (DEC10-VEN) VS. INTENSIVE CHEMOTHERAPY (IC) IN ACUTE MYELOID LEUKEMIA (AML): A PROPENSITY SCORE MATCHED ANALYSIS STRATIFIED BY RISK OF TREATMENT-RELATED MORTALITY
Author(s): ,
Abhishek Maiti
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States
,
Courtney DiNardo
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States
,
Tapan Kadia
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States
,
Caitlin Rausch
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Naveen Pemmaraju
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Naval Daver
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Gautam Borthakur
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Kiran Naqvi
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Maro Ohanian
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Nicholas Short
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Yesid Alvarado
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Koichi Takahashi
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Musa Yilmaz
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Nitin Jain
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Steven Kornblau
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Koji Sasaki
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Michael Andreeff
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Prithiviraj Bose
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Alessandra Ferrajoli
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Ghayas Issa
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Elias Jabbour
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Lucia Masarova
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Philip Thompson
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Sherry Pierce
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Guillermo Garcia-Manero
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Farhad Ravandi
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
John Welch
Affiliations:
Washington University School of Medicine at St. Louis,St. Louis,United States
,
Wei Qiao
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Jing Ning
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
,
Hagop Kantarjian
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States
Marina Konopleva
Affiliations:
Department of Leukemia,The University of Texas MD Anderson Cancer Center,Houston,United States
EHA Library. Maiti A. 06/12/20; 294961; S141
Dr. Abhishek Maiti
Dr. Abhishek Maiti
Contributions
Abstract

Abstract: S141

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: AML therapy

Background
Hypomethylating agents (HMA) with VEN has emerged as a new standard for older patients (pts) with AML. However, it is unknown how VEN+HMA compares to IC in “fitter” pts. Additionally, outcomes with HMA+VEN is unknown for pts deemed at particularly high risk for treatment-related mortality (TRM) by objective methods.

Aims
To compare outcomes of older pts with AML receiving DEC10-VEN vs. IC, overall and after stratification by ‘fitness’ for IC using a validated TRM risk model. 

Methods
Frontline HMA+VEN pts received DEC10-VEN (phase 2 trial, NCT03404193) comprising 10 day (d) DEC 20 mg/m2 with daily VEN for induction, and 5d DEC with VEN as consolidation (Maiti et al. Blood 2019;134:263). The IC cohort were treated at a single institution between 2000-2018 with regimens containing ≥1 g/m2/d of ara-C. Pts with ELN favorable cytogenetics were excluded. The validated TRM score (TRMS) incorporating 8 clinical variables with a cut-off >13.1 was used to classify pts at high risk of TRM with IC (Walter et al. J Clin Oncol 2011). Propensity score matching (PSM) using age, ECOG performance status (PS), ELN risk group and high (>13.1) vs low TRMS was used for 1:2 matching. Stratified Cox model was used to compare outcomes.

Results
Median age of DEC10-VEN group (n=85) was 72 yrs (range 63-89), 5% pts had ECOG PS≥3, 65% pts had ELN adverse risk AML, 28% pts had high TRMS, 15% pts underwent allogeneic stem-cell transplantation (SCT) and median follow-up (FU) was 16 months (mo). Median age of the IC cohort (n=170) was 67 yrs (range 54-86), 7% pts had ECOG PS≥3, 58% pts had ELN adverse risk AML, 28% pts had high TRMS, 18% pts underwent SCT, 62% pts were treated on a clinical trial and median FU was 55 mo. In the overall population, DEC10-VEN showed superior CR/CRi, lower TRM and longer overall survival (OS) compared to IC (Fig 1a). Median OS with DEC10-VEN in the low TRMS group was 15.1 mo and in the high TRMS group was 9.1 mo (Fig 1b,c). CR/CRi was 82% with DEC10-VEN vs. 59% with IC (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.65, 6.16, stratified p=0.001). 30d mortality was 1.2% with DEC10-VEN vs. 15% with IC (OR 0.07, 95% CI 0.01, 0.49, stratified p=0.008). Stratified analysis by TRM risk showed DEC10-VEN outcomes were superior to IC in pts at high risk of TRM and not statistically different from IC in pts at low risk of TRM (Table 1). Additional subgroup analyses by clinical and biological characteristics will be presented.

Table 1. Outcomes with DEC10-VEN vs. IC in AML by risk of TRM [values expressed as n(%)]

High risk of TRM (>13.1)

DEC10-VEN N=24

IC N=48

OR, or HR

95% CI

Stratified p

CR/CRi

17 (71)

17 (65)

4.00 (1.34, 11.44)

0.01 

Mortality 30d

0

16 (33)

NA

NA

               60d

4 (17)

21 (44)

0.17 (0.04, 0.81)

0.03

OS, mo

9.1

2.4

0.30 (0.13, 0.69)

0.01

Low risk of TRM (≤13.1)

N=61

N=122

 

 

CR/CRi

52 (87)

88 (72)

2.50 (1.08, 5.74)

0.03

Mortality 30d

1 (2)

8 (7)

0.22 (0.03, 1.87)

0.17

               60d

2 (3)

16 (13)

0.22 (0.05, 1.00)

0.05

OS, mo

15.1

11.2

0.75 (0.45, 1.26)

0.28

 Fig. 1 OS in older pts with AML with DEC10-VEN vs IC

Conclusion
DEC10-VEN shows superior outcomes compared to IC in older pts with AML in a PSM analysis. Benefits were most pronounced in pts at high risk of TRM.

Session topic: 04. Acute myeloid leukemia - Clinical

Keyword(s): Acute myeloid leukemia, BCL2, Decitabine, Treatment-related mortality

Abstract: S141

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: AML therapy

Background
Hypomethylating agents (HMA) with VEN has emerged as a new standard for older patients (pts) with AML. However, it is unknown how VEN+HMA compares to IC in “fitter” pts. Additionally, outcomes with HMA+VEN is unknown for pts deemed at particularly high risk for treatment-related mortality (TRM) by objective methods.

Aims
To compare outcomes of older pts with AML receiving DEC10-VEN vs. IC, overall and after stratification by ‘fitness’ for IC using a validated TRM risk model. 

Methods
Frontline HMA+VEN pts received DEC10-VEN (phase 2 trial, NCT03404193) comprising 10 day (d) DEC 20 mg/m2 with daily VEN for induction, and 5d DEC with VEN as consolidation (Maiti et al. Blood 2019;134:263). The IC cohort were treated at a single institution between 2000-2018 with regimens containing ≥1 g/m2/d of ara-C. Pts with ELN favorable cytogenetics were excluded. The validated TRM score (TRMS) incorporating 8 clinical variables with a cut-off >13.1 was used to classify pts at high risk of TRM with IC (Walter et al. J Clin Oncol 2011). Propensity score matching (PSM) using age, ECOG performance status (PS), ELN risk group and high (>13.1) vs low TRMS was used for 1:2 matching. Stratified Cox model was used to compare outcomes.

Results
Median age of DEC10-VEN group (n=85) was 72 yrs (range 63-89), 5% pts had ECOG PS≥3, 65% pts had ELN adverse risk AML, 28% pts had high TRMS, 15% pts underwent allogeneic stem-cell transplantation (SCT) and median follow-up (FU) was 16 months (mo). Median age of the IC cohort (n=170) was 67 yrs (range 54-86), 7% pts had ECOG PS≥3, 58% pts had ELN adverse risk AML, 28% pts had high TRMS, 18% pts underwent SCT, 62% pts were treated on a clinical trial and median FU was 55 mo. In the overall population, DEC10-VEN showed superior CR/CRi, lower TRM and longer overall survival (OS) compared to IC (Fig 1a). Median OS with DEC10-VEN in the low TRMS group was 15.1 mo and in the high TRMS group was 9.1 mo (Fig 1b,c). CR/CRi was 82% with DEC10-VEN vs. 59% with IC (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.65, 6.16, stratified p=0.001). 30d mortality was 1.2% with DEC10-VEN vs. 15% with IC (OR 0.07, 95% CI 0.01, 0.49, stratified p=0.008). Stratified analysis by TRM risk showed DEC10-VEN outcomes were superior to IC in pts at high risk of TRM and not statistically different from IC in pts at low risk of TRM (Table 1). Additional subgroup analyses by clinical and biological characteristics will be presented.

Table 1. Outcomes with DEC10-VEN vs. IC in AML by risk of TRM [values expressed as n(%)]

High risk of TRM (>13.1)

DEC10-VEN N=24

IC N=48

OR, or HR

95% CI

Stratified p

CR/CRi

17 (71)

17 (65)

4.00 (1.34, 11.44)

0.01 

Mortality 30d

0

16 (33)

NA

NA

               60d

4 (17)

21 (44)

0.17 (0.04, 0.81)

0.03

OS, mo

9.1

2.4

0.30 (0.13, 0.69)

0.01

Low risk of TRM (≤13.1)

N=61

N=122

 

 

CR/CRi

52 (87)

88 (72)

2.50 (1.08, 5.74)

0.03

Mortality 30d

1 (2)

8 (7)

0.22 (0.03, 1.87)

0.17

               60d

2 (3)

16 (13)

0.22 (0.05, 1.00)

0.05

OS, mo

15.1

11.2

0.75 (0.45, 1.26)

0.28

 Fig. 1 OS in older pts with AML with DEC10-VEN vs IC

Conclusion
DEC10-VEN shows superior outcomes compared to IC in older pts with AML in a PSM analysis. Benefits were most pronounced in pts at high risk of TRM.

Session topic: 04. Acute myeloid leukemia - Clinical

Keyword(s): Acute myeloid leukemia, BCL2, Decitabine, Treatment-related mortality

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