TP53 mutations occur in nearly 10% of adults with de novo acute myeloid leukaemia (AML); however, these mutations are encountered at higher frequency in therapy-related AML (t-AML)(~ 35%) and AML with complex cytogenetics (50–60%)(Ok, et al 2015, Rucker, et al 2012). The presence of the TP53 mutation (TP53m) conveys an extremely poor prognosis (Grossmann, et al 2012, Rucker, et al 2012). Patients with TP53m AML are generally older in age (Rucker, et al 2012), and their physical fitness, especially in those with t-AML, is poor (Granfeldt Ostgard, et al 2015). The clinical response of TP53m AML to standard induction regimens has been disappointing, and if achieved, is usually short-lived (Grossmann, et al 2012, Rucker, et al 2012).

Venetoclax (VEN) has shown encouraging activity when combined with hypomethylating agents (HMAs) in both newly diagnosed and relapsed/refractory (r/r) AML (Aldoss, et al 2018, DiNardo, et al 2019). The combination is well-tolerated even in frail patients and is associated with low treatment-related mortality (TRM)(DiNardo, et al 2019). Apoptosis mediated by venetoclax appears to be TP53-independent (Anderson, et al 2016), and