Acute Myeloid Leukemia Coverage From Every Angle

Early Results With Eftozanermin Alfa Plus Venetoclax in AML

By: Lauren Harrison, MS
Posted: Monday, October 26, 2020

The next-generation tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptor eftozanermin alfa appeared to be well tolerated with antitumor activity in patients with relapsed or refractory acute myeloid leukemia (AML) when combined with venetoclax. Mojca Jongen-Lavrencic, MD, PhD, of Erasmus MC Cancer Institute in Rotterdam, the Netherlands, presented this work on behalf of her colleagues at the 2020 Society of Hematologic Oncology (SOHO) Annual Meeting (Abstract AML-058).

This phase I study recruited 34 adults with either relapsed or refractory AML or diffuse large B-cell lymphoma. These patients received intravenous eftozanermin in doses of 1.25, 3.75, or 7.5 mg/kg in the monotherapy group or 3.75 or 7.5 mg/kg when combined with 400 or 800 mg of daily oral venetoclax. Eftozanermin alfa was administered on days 1, 8, and 15 of a 21-day cycle. There were 4 patients with AML who were assigned to receive eftozanermin alfa monotherapy and 19 patients with AML who received eftozanermin alfa plus venetoclax.

Patients completed a median of one cycle with eftozanermin alfa monotherapy and a median of three cycles with combination therapy, with four patients completing five or more combination treatment cycles. No patients in the monotherapy cohort responded to treatment. In contrast, the overall response rate among patients who received the combination was 21%, including three complete responses (two with 3.75 mg/kg, one with 7.5 mg/kg).

Treatment-emergent adverse events were noted in all patients, regardless of treatment, and all patients had grade 3 or higher adverse events. The most common grade 3 or higher adverse event included increased levels of alanine and aspartate aminotransferases. Five patients in the combination therapy group experienced serious adverse events related to eftozanermin alfa. Eftozanermin alfa was found to bind and saturate death receptors on neutrophils within 2 hours after dosing. The desaturation of the receptors was time-dependent.

Disclosure: The study authors did not provide any disclosure information at the time of publication.

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