Patients with higher risk myelodysplastic syndromes (MDS) were treated with magrolimab plus azacitidine in a phase Ib study. Responses were observed in patients harboring TP53 mutations, as well as those who were TP53 wild type. Investigators noted a lower-than-expected rate of discontinuation due to adverse events (AEs). David A. Sallman, MD, of Moffitt Cancer Center in Florida, reported the results at the European Hematology Association (EHA) 2022 Congress. Results were also shared at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting.
Magrolimab, a monoclonal antibody against CD47, induces macrophage-mediated phagocytosis of tumor cells. Its effect appears to be synergistic with the chemotherapeutic agent azacitidine. The present phase Ib study was designed to assess safety, tolerability, and efficacy of magrolimab with azacitidine as documented by complete remission rate. Secondary objectives included efficacy in combination with azacitidine as determined by objective response rate, duration of complete response, duration of response, hemoglobin increase on treatment, progression-free survival, relapse-free survival, event-free survival, and red blood cell transfusion independence.
Patients (n=95) received a median of six treatment cycles (range = 1-27), had a mean age of 69 years (range = 28-91), and the majority were Eastern Cooperative Oncology Group Performance Scale (ECOG PS) 0 or 1. One-third of patients (36.8%) received hematopoietic cell transplantation (HCT) and 14.7% progressed to acute myeloid leukemia. The main reasons for treatment discontinuation were HCT, progressive disease, and AEs.
Six patients stopped treatment because of AEs. The most frequently reported treatment-emergent adverse events (TEAEs) were constipation (68%), thrombocytopenia (55%), anemia (52%), neutropenia (47%), nausea (46%), and diarrhea (44%). For grade 3 and 4 TEAEs, the most common were anemia (47%), neutropenia (46%), thrombocytopenia (46%), and decreased white blood cell count (30%).
The median hemoglobin change from baseline was -0.7 g/dL at first post-treatment visit, with a maximum of -1.1 g/dL between doses one and two, -0.5 g/dL between doses two and three, and -1.2 g/dL between doses one and three. While many patients had grade 4 anemia, the investigators determined the anemia was not related to the therapy. Patients with anemia were managed with a low priming dose, intrapatient dose escalation, and supportive care with red blood cell transfusions. One-third of patients who were transfusion-dependent at baseline became transfusion independent after treatment.
The investigators documented a 30-day mortality of 2% with no additional deaths at 60 days. Eight patients died because of TEAEs, including pneumonia, COVID-19, intracranial hemorrhage, leukemia, myocardial ischemia, pulmonary embolism, and sepsis. A small percentage of patients (2.2%) treated with magrolimab developed transient anti-drug antibodies.
The objective response rate was 74.7%. One-third of patients (32.6%) demonstrated complete remission (31.1% of patient with TP53 wild type and 40% of patients with TP53 mutation) and one-third of patients (31.6%) had a marrow complete response.
The phase III ENHANCE trial will continue to evaluate the use of magrolimab plus azacitidine in patients with higher risk MDS.
Any conflicts of interest by the authors were made public at the time of presentation.
Reference
Sallman DA, Al Malki MM, Asch AS, at al. Magrolimab in combination with azacitidine for untreated higher risk myelodysplastic syndromes (HR-MDS): 5F9005 phase 1b study results. Poster 7017. Presented at the European Hematology Association (EHA) 2022 Congress, June 12, 2022; Vienna, Austria.