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TOPLINE:

Adding magrolimab to venetoclax and azacitidine did not improve overall survival or complete remission rates in patients with previously untreated acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy. The phase 3 ENHANCE-3 study was stopped early at interim analysis due to futility, with more fatal adverse events observed in the magrolimab arm.

METHODOLOGY:

• A total of 378 patients with histologically confirmed AML per 2016 World Health Organization criteria and who were ineligible for intensive chemotherapy were randomized 1:1 to receive magrolimab or placebo plus venetoclax and azacitidine.
• Participants aged 75 years or older or 18-74 years with specific comorbidities including Eastern Cooperative Oncology Group performance status score of 2-3, impaired organ function, or other conditions incompatible with intensive chemotherapy were included.
• Treatment consisted of magrolimab (1 mg/kg on days 1 and 4, 15 mg/kg on day 8, 30 mg/kg on days 11 and 15, then weekly for five doses, followed by 30 mg/kg every 2 weeks) or placebo, plus venetoclax (100 mg on day 1, 200 mg on day 2, 400 mg daily thereafter) and azacitidine (75 mg/m² on days 1-7) in 28-day cycles.

TAKEAWAY:

• At final analysis with a median follow-up of 7.62 months in the magrolimab arm and 7.36 months in the control arm, the median overall survival was 10.7 months (95% CI, 8.7-14.9) and 14.1 months (95% CI, 9.7 to not estimable), respectively (hazard ratio, 1.178; 95% CI, 0.848-1.637; P = .3276).
• Treatment-related serious adverse events were higher in the magrolimab arm than in the control arm (46.0% vs 39.1%), with more treatment-emergent adverse events leading to death (19.0% vs 11.4%).
• Grade 5 infections occurred more frequently with magrolimab than with control (11.1% vs 6.5%), including higher rates of pneumonia (3.7% vs 2.2%) and sepsis (6.9% vs 3.3%), while five patients (2.6%) in the magrolimab arm had grade 5 respiratory failure vs none in the control arm.
• Mortality rates were higher in the magrolimab arm than in the control arm at 30 (6.9% vs 4.3%) and 60 (14.8% vs 9.8%) days.

IN PRACTICE:

“ENHANCE-3 was the first randomized phase 3 trial to evaluate an anti-CD47 therapy in frontline AML for patients ineligible for IC [intensive chemotherapy] and the first randomized trial in this setting to use venetoclax and azacitidine as a comparator since the United States accelerated approval of this combination in 2018. In this study, the addition of magrolimab to venetoclax and azacitidine did not improve OS [overall survival], and the study was stopped early because the prespecified futility boundary for OS was crossed at an interim analysis,” the authors of the study wrote.

SOURCE:

This study was led by Naval Daver, The University of Texas MD Anderson Cancer Center, Houston. It was published online in Blood.

LIMITATIONS:

According to the researchers, the reasons for increased fatal infections with magrolimab addition were unclear, given similar incidences of any-grade infections, febrile neutropenia, and drug interruptions between treatment arms. The protocol encouraged but did not mandate infection prophylaxis for patients with prolonged neutropenia or at risk. A higher proportion of patients in the magrolimab arm had adverse genetic risk per European LeukemiaNet 2017 criteria than in the control arm (44.4% vs 35.4%), which may have affected efficacy outcomes.

DISCLOSURES:

The ENHANCE-3 study was funded by Gilead Sciences, Inc. Medical writing support was provided by Ashfield MedComms, an Inizio Company, and was funded by Gilead Sciences, Inc.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.