Venetoclax plus hypomethylating agents for the treatment of patiemts with acute myeloid leukemia

Venetoclax (VEN) is a selective BCL-2 inhibitor that has been shown to be effective when used in combination with hypomethylating agents (HMAs) or, at less extent, low-dose cytarabine (LDAC) for the treatment of elderly patients with acute myeloid leukemia (AML), who are unfit for intensive chemotherapy (IC). In particular, complete remission rates (CR) and median survival in selected molecular subgroups approximate or also exceed those currently achievable with conventional IC , raising the question of the possible use of VEN-HMA in patients potentially eligible to IC, including young adult ones. However, while enthusiasm and excitation for these results seem to be fully justified, a number of questions still remain unresolved: (1) will data of phase 1-2 studies and registration studies be reproduced in the real world? (2) which unfitness criteria would be adopted for the definition of  the ideal candidates to receive the combination? (3) Should all patients with unfavorable molecular findings at presentation, mostly those with cocnomitant TP53 mutation and complex karyotype, independently from age, receive Ven/HMA? (4) How tos elect between azacitidine (AZA) or decitabine (DEC) in combination with Ven? (5) Is Ven/HMA therapy an ideal bridge to allogeneic transplantation?

Author(s): Felicetto Ferrara

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