Venetoclax plus hypomethylating agents in favourable-risk AML

Venetoclax plus hypomethylating agents was associated with a promising remission rate of 80% with durable responses in patients with favourable-risk acute myeloid leukaemia (AML). Most responders achieved measurable residual disease (MRD) negativity. Patients with prior hypomethylating agent use had a lower response rate. Nonetheless, more than half of these patients responded despite the majority being relapsed/refractory (R/R) [1].

Among older and unfit patients with untreated AML, treatment with venetoclax plus hypomethylating agents is associated with a high composite remission rate, which consists of complete remission (CR) and complete remission with incomplete recovery (CRi). Nevertheless, data regarding the activity of venetoclax plus hypomethylating agents in those patients with favourable-risk AML is scarce, particularly in those with core-binding factor (CBF) alterations.

Dr Shukaib Arslan (City Of Hope Helford Clinical Research Hospital, California, USA) retrospectively analysed outcomes of 46 patients with favourable-risk AML who underwent therapy with venetoclax plus hypomethylating agents at 4 academic cancer centres. Favourable-risk AML was defined by the presence of either CBF alterations, NPM1 mutations in the absence of FLT3-ITD mutations; or bi-allelic CEBPA mutations.

The CR/CRi rate among the whole cohort was 80%, including 52% CR and 28% CRi. There was no significant difference in CR/CRi rate between newly diagnosed and R/R patients (88% vs 70%; P=0.15). However, patients with history of prior hypomethylating agent exposure had a lower response rate compared with hypomethylating agent-naïve patients (55% vs 88%; P=0.025). No difference in response was observed based on the favourable genetic alteration subgroups: 80% in CBF, 86% in NPM1-mutated, and 77% in CEBPA-mutated (P=0.44). Furthermore, no difference in response was observed according to patient age, AML types (de novo vs secondary), prior transplant, or the type and schedule of hypomethylating agents. The median overall survival for the whole cohort was 18 months. Median leukaemia-free survival was 13.2 months for all responders, 11.2 months for newly diagnosed responders, and 14.0 months for R/R responders (P=0.986). The 30- and 60-day mortality for the whole cohort was 0% and 9%, respectively.

1. Arslan S, et al. Outcomes of Therapy with Venetoclax Combined with Hypomethylating Agents in Favorable-Risk Acute Myeloid Leukemia (AML). 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 994.

Posted on 18 February 202122 February 2021