In early December 2020, biopharmaceutical company Gilead Sciences, Inc. (“Gilead”) shared updated results from a Phase 1b clinical trial evaluating magrolimab for patients with treatment-naïve acute myeloid leukemia (AML). Generally, the patients included in this trial are not eligible for other forms of treatment, such as first-line chemotherapy. As a result, magrolimab offers a potential better option for those with AML, particularly those with TP53 gene mutations. The data on the sustained clinical responses was presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition under Abstract 330.

Magrolimab

As an investigational treatment, magrolimab is currently not approved for treatment use. Additionally, researchers are not yet sure on the safety or efficacy of magrolimab. However, the treatment shows potential benefit – and clinical responses – for those with AML. Magrolimab is a monoclonal antibody against CD47 and a macrophage checkpoint inhibitor. According to the American Cancer Society, monoclonal antibodies are:

man-made proteins that act like human antibodies in the immune system. There are 4 different ways they can be made and are named based on what they are made of: murine (made of mouse proteins and the names of treatments end in -omab), chimeric (a combination of part mouse and part human and the name of treatments end in -ximab), humanized (made from small parts of mouse proteins attached to human proteins and the names of treatments end in -zumab), and human (fully human proteins and the names of treatments end in -umab).

In this case, these antibodies help target CD47 and prevent cancer cells from protecting themselves against macrophages. Outside of being explored for AML, researchers are also looking at magrolimab as a potential treatment for solid tumors and myelodysplastic syndromes (MDS). Additionally, magrolimab, in conjunction with azacitidine, received Breakthrough Therapy and PRIME designations for the treatment of patients with MDS; and Fast Track and Orphan Drug designations for the treatment of AML, MDS, DLBCL, and follicular lymphoma.

The Trial

Within the Phase 1b clinical trial, researchers evaluated magrolimab with azacitidine for patients with treatment-naive (previously untreated) AML. Altogether, 64 patients enrolled in the study. Of these, 47 (73.4%) had TP53 gene mutations. Typically, these gene mutations are associated with treatment-averse AML and poor patient outcomes. Initially, all patients received a starter dose of 1mg/kg magrolimab, which was followed by a full dose of azacitidine and maintenance doses of 30/mg magrolimab either weekly or bi-weekly.

Overall, 63% of patients being used to evaluate the drug’s efficacy received some sort of response by November; 42% experienced complete remission, and 12% achieved complete remission with an incomplete count recovery. Of the patients with TP53 gene mutations, which are typically the more difficult patients to treat, 69% received some sort of response, with 45% achieving complete remission, and 14% achieving complete remission with incomplete count recovery.

Although the treatment was fairly well-tolerated, side effects included:

• Anemia
• Neutropenia (low white blood cell count)
• Thrombocytopenia (low platelet count)
• Infusion site reaction
• Higher blood bilirubin levels
• Fatigue

Overall, 3 patients discontinued from the trial due to drug-related side effects. Within 1 month, 3 patients died; 2 additional ones died by the end of month two. However, as the deaths were considered “all-cause mortality,” they were not necessarily directly related to treatment.

Overall, the survival rate for those without TP53 mutations was 18.9 months (slightly over 1.5 years) and 12.9 months (slightly over 1 year) for those with these mutations.

Acute Myeloid Leukemia (AML)

When the DNA of developing cells is damaged, these cells become immature and can cause health issues. In the case of acute myeloid leukemia (AML), a blood and bone marrow cancer, the bone marrow produces immature cells which eventually develop into myeloblasts, or leukemic white blood cells. When these abnormal, cancerous cells force out healthy blood cells, it inhibits blood health and bodily function. Symptoms of AML include:

• Fever
• Pallor (pale skin)
• Frequent infections
• Easy bruising and bleeding
• Fatigue
• Shortness of breath / difficulty breathing
• Appetite loss
• Unintended weight loss
• Bone pain