In a phase Ib trial (5F9005) reported in the Journal of Clinical Oncology, David A. Sallman, MD, and colleagues found that the combination of magrolimab and azacitidine showed activity in previously untreated patients with intermediate- to very high–risk myelodysplastic syndromes (MDS).
As stated by the investigators, “Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a don’t-eat-me signal overexpressed on cancer cells. Cluster of differentiation 47 blockade by magrolimab promotes macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine, which increases expression of eat-me signals.”
David A. Sallman, MD
Study Details
In the multicenter trial, 95 patients enrolled between July 2018 and August 2020 were treated with magrolimab at a 1 mg/kg priming dose followed by ramp-up to a 30 mg/kg once weekly or a once-every-2-week maintenance dose; azacitidine at 75 mg/m2 was given on days 1 to 7 of each 28-day cycle. The primary endpoints of the study were safety/tolerability and complete remission rate.
Responses
Among all 95 patients, complete remission was achieved in 32.6% (95% confidence interval [CI] = 23.4%–43.0%) and partial remission or better was achieved in 74.7%. Median time to response was 1.9 months. Median durations of response were 11.1 months (95% CI = 7.6–13.4 months) among those with complete remission and 9.8 months (95% CI = 8.8–12.9 months) among all those with objective response.
Median progression-free survival was 11.6 months (95% CI = 9.0–14.0 months). Median overall survival was not reached (95% CI = 16.3 months to not reached) after a median follow-up of 17.1 months (interquartile range = 10.8–21.2 months).
Among 25 patients with a TP53 mutation, complete remission was achieved in 40.0% and partial remission or better was seen in 68.0%. Median durations of response were 7.6 months in those with complete remission and 9.2 months among all responders. Median progression-free survival was 11.0 months, and median overall survival was 16.1 months (95% CI = 10.8 months to not reached).
Among 61 patients with wild-type TP53, complete remission was achieved in 31.1% and partial response or better was seen in 78.7%. Median durations of response were 12.9 months in those with complete remission and 9.8 months among all responders. Median progression-free survival was 11.8 months, and median overall survival was not reached (95% CI = 21.3 months to not reached).
A total of 34 patients (36%) underwent allogeneic stem cell transplantation, with a 2-year overall survival rate of 77%.
KEY POINTS
- Magrolimab plus azacitidine produced complete remission in 33% of patients and overall objective response in 75%.
- Good outcomes were observed in patients with a TP53 mutation.
Adverse Events
The most common adverse events of any grade were constipation (68%), thrombocytopenia (55%), anemia (52%), neutropenia (47%), nausea (46%), and diarrhea (43%). The most common grade 3 or 4 adverse events were anemia (47%), neutropenia (46%), and thrombocytopenia (46%). Median change in hemoglobin from baseline to first post-dose assessment was –0.7 g/dL (range = –3.1 to 2.4 g/dL). The most common serious adverse events were febrile neutropenia (24%), pneumonia (9%), anemia (8%), bacteremia (6%), pyrexia (5%), and infusion-related reactions (5%).
The investigators concluded, “Magrolimab plus azacitidine was well tolerated with promising efficacy in patients with untreated higher-risk MDS, including those with TP53 mutations. A phase III trial of magrolimab/placebo plus azacitidine is ongoing (ENHANCE: NCT04313881).”
Dr. Sallman, of Moffitt Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Gilead Sciences, Inc. For full disclosures of the study authors, visit ascopubs.org.
