Joshua Zeidner, MD, an Associate Professor of Medicine and Chief of Leukemia Research, published a paper in the journal Blood. Titled “Magrolimab plus azacitidine vs physician’s choice for untreated TP53-mutated acute myeloid leukemia: the ENHANCE-2 study,” he聽looked at a global randomized phase 3 study in acute myeloid leukemia (AML).
This study examined patients with TP53-mutated AML who have an extremely poor prognosis without any known effective therapies. Historically, average overall survival is approximately 5-6 months in patients with newly diagnosed TP53-mutated AML. Magrolimab is an investigational monoclonal antibody targeting CD47 which promotes phagocytosis (or the eating and destruction) of cancer cells. In an early phase 1b study, the combination of azacitidine and magrolimab was demonstrated to be safe with very promising clinical activity in patients with newly diagnosed TP53-mutated AML with complete remission rates of 32% and average overall survival of 10 months (https://pubmed.ncbi.nlm.nih.gov/37703506/).
These promising results led to the development of a global phase 3 clinical trial comparing two treatment options for newly diagnosed TP53-mutated AML. One group received azacitidine with the investigational drug magrolimab, while the other received a treatment chosen by their physician鈥攅ither azacitidine with venetoclax or intensive chemotherapy (7+3).
In the planned comparison between azacitidine with magrolimab and azacitidine with venetoclax, 205 patients were randomly assigned to one of the two groups. However, an interim analysis led to the study being halted due to futility. Patients receiving azacitidine with magrolimab had an average overall survival of 4.4 months, compared to 6.6 months for those receiving azacitidine with venetoclax.
This is the first published randomized trial for TP53-mutated AML, a patient group with a high need for new treatments. The results confirm the limited effectiveness of standard therapies for this population and provide a benchmark for future research.