VIALE-A: newly diagnosed chemo-ineligible AML

The practice-changing randomised double-blind phase 3 VIALE-A trial established venetoclax and azacitidine as a new standard of care for induction therapy in older patients with acute myeloid leukemia (AML).

Older adults diagnosed with AML who are ineligible for intensive treatment often receive lower-intensity therapies, such as azacitidine or decitabine, which only provide an expected median survival of 9-10 months and complete remission (CR) / CR with incomplete bone marrow recovery (CRi) rates <40%.

Dr Courtney Di Nardo (MD Anderson Cancer Centre, USA) presented the results of the VIALE-A study, which evaluated the efficacy of a combination regimen of azacitidine and venetoclax in older treatment-naïve AML patients (n=431) who were ineligible for intensive therapy [1]. The co-primary endpoints were overall survival (OS) and percentage of participants with CR with or without CRi. Patients were randomised in a 2:1 ratio to the combination regimen or to azacitidine plus placebo.

With a median follow-up of 20.5 months, both primary endpoints were met. The combination of azacitidine and venetoclax led to improved OS (14.7 vs 9.6 months; HR 0.66; 95% CI 0.52-0.85; P<0.001), and improved response rates CR/CRi (66% vs 28%; P<0.001), compared with azacitidine alone. Furthermore, responses were quicker; the median time to first CR/CRi response was 1.3 and 2.8 months, respectively. The duration of CR/CRi was 17.5 months and 13.4 months, respectively. There was also a higher rate of transfusion independence in the azacitidine with venetoclax arm (60% vs 35%). The benefit of venetoclax combined with azacitidine was observed across all key subgroups.

The safety profile included cytopenias, and in particular neutropenia/febrile neutropenia. Dr Di Nardo recommended waiting until the end of cycle 1 to determine whether dose delay or modifications are required. In conclusion, the results from this study demonstrated that, compared with azacitidine and placebo, patients receiving azacitidine and venetoclax as standard induction therapy had improved OS, better rates of CR and composite remission, faster time to first remission, improved duration of remission, and higher rates of transfusion independence. Collectively, these data confirm azacitidine and venetoclax as a new standard of care.

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   1. Di Nardo C et al. VIALE-A: A Randomized, Double-blind, Placebo-Controlled Study of Venetoclax with Azacitidine vs Azacitidine in Treatment-naïve Patients with Acute Myeloid Leukaemia Ineligible for Intensive Chemotherapy. EHA25 Virtual, 11-21 June 2020, Abstract LB2601.

Posted on 9 September, 202023 February, 2021