High-risk patients with TP53-mutated acute myeloid leukaemia (AML) have limited treatment options and very poor prognoses.

Magrolimab is a monoclonal antibody designed to block CD47 — an immune macrophage checkpoint molecule that signals “don’t eat me,” thereby allowing leukaemia cell destruction.

Combining magrolimab with the hypomethylating agent azacitidine (AZA) helped eliminate tumour cells by increasing the number of “eat me” signals in preclinical studies.

In a Phase Ib trial presented by Naval Daver, M.D., researchers evaluated the safety, efficacy and tolerability of this combination in 72 patients with newly diagnosed high-risk TP53-mutated AML. The objective response rate (ORR) was 48.6% and the complete response rate was 33.3%.

Median time to ORR was 2.2 months. Median CR duration was 7.7 months and median overall survival was 10.8 months.

Common side effects included constipation, diarrhoea, febrile neutropenia, nausea and fatigue.

The findings suggest this combination has a favourable safety profile and encouraging early results. A Phase III trial currently is underway to compare this treatment to the current standard of care therapies in newly diagnosed TP53 AML. 

Source: European Hematology Association (EHA) 2022 Congress