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DEC10-VEN superior to intensive chemotherapy in high-risk AML

Presented By
Dr Abhishek Maiti, University of Texas MD Anderson Cancer Centre, USA
EHA 2020
Phase 2

10-day decitabine and venetoclax (DEC10-VEN) showed superior outcomes compared with intensive chemotherapy in older patients with acute myeloid leukaemia (AML) in a propensity score matching analysis. Benefits were most pronounced in patients at high risk of treatment-related mortality (TRM).

The results of the phase 2 trial were presented by Dr Abhishek Maiti (University of Texas MD Anderson Cancer Centre, USA) [1]. This study addressed the question of how venetoclax + decitabine compared with intensive chemotherapy in patients stratified by TRM, as assessed by a validated TRM risk model [2]. The primary endpoint was overall response rate (ORR). Key secondary outcomes included duration of response, disease-free survival, and overall survival (OS).

Frontline AML patients (n=255) received either DEC10-VEN comprising 10 days decitabine 20 mg/m2 with daily venetoclax for induction, and 5 days decitabine with venetoclax as consolidation (n=85) or intensive chemotherapy (regimens containing ≥1 g/m2/day of cytosine arabinoside; n=170). Propensity score matching used age, Eastern Cooperative Oncology Group (ECOG) performance status, cytogenetics risk group, and high versus low TRM score (cut-off 13.1).

With a median follow up of 55 months, the DEC10-VEN arm showed superior complete remission with or without incomplete haematologic recovery (CR/CRi), lower TRM, and longer OS compared with intensive chemotherapy (see Table). Median OS with DEC10-VEN in the group with low TRM scores was 15.1 months; 9.1 months in the group with high TRM scores. CR/CRi was 82% with DEC10-VEN as opposed to 59% with intensive chemotherapy (odds ratio [OR] 3.19; 95% CI 1.65- 6.16; stratified P=0.001). 30-day mortality was 1.2% with DEC10-VEN versus 15% with intensive chemotherapy (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 intensive chemotherapy in patients at high risk of TRM; however, in patients at low risk of TRM, the data were not statistically different from intensive chemotherapy.

In conclusion, stratifying patients with a validated TRM score has shown that first-line DEC10-VEN is superior to intensive chemotherapy for patients determined to be at high TRM risk. However, it should be noted that although a propensity matching analysis is one of the best ways of comparing a treatment with a historical control, it has the danger of introducing bias and can never replace a randomised prospective study.

Table. Outcomes with DEC10-VEN versus IC in AML by risk of TRM [1]

* values expressed as n(%)

    1. Maiti A, et al. 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. EHA25 Virtual, 11-21 June 2020, Abstract S141.
    2. Walter RB, et al. Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. J Clin Oncol. 2011;29(33):4417-4423.

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