Elotuzumab May Slow Multiple Myeloma

Adding the monoclonal antibody elotuzumab to standard therapy reduced the risk of disease progression by 30% in patients with relapsed or refractory multiple myeloma. These preliminary findings were presented at a press briefing highlighting research that will be discussed at the American Society of Clinical Oncology's Annual Meeting, to be held May 29–June 2 in Chicago, IL.

In the phase III ELOQUENT-2 trial, 646 patients with relapsed or refractory multiple myeloma were randomized to receive either standard therapy—a combination of the thalidomide derivative lenalidomide (Revlimid; Celgene) and the corticosteroid dexamethasone—or standard therapy plus elotuzumab (Bristol-Myers Squibb/ AbbVie). Of the patients who remained on therapy at 24 months, median progression-free survival (PFS) was 19.4 months in the elotuzumab group compared with 14.9 months in the standard therapy group. Overall response rate was 79% in the intervention group versus 66% in the control arm.

“Over the last decade or so several new drugs have been approved for relapsed or refractory multiple myeloma, but many are newer versions of existing classes of drugs, such as proteasome inhibitors,” said the study's principal investigator Sagar Lonial, MD, chief medical officer at the Winship Cancer Institute at Emory University School of Medicine in Atlanta, GA. With this study, “we have sought out a new class of drugs focusing on immune-targeted approaches to killing plasma cells.”

Elotuzumab works by targeting the protein SLAMF7, which is expressed on the surface of multiple myeloma cells as well as on natural killer (NK) and other immune cells. SLAMF7 enhances activation of NK cells, but only in the presence of the adapter protein EAT-2, which is expressed in NK cells but not in multiple myeloma cells.

“Elotuzumab targets myeloma cells and sets them up for cell-mediated antibody-dependent cellular cytotoxicity-based death,” said Lonial. “Once it binds to SLAMF7, it activates NK cells, allowing them to go after the tumor cells that have been targeted with elotuzumab.”

In ELOQUENT-2, some benefit was observed across all age groups and among a high-risk genetic subset of patients—those with 17p deletion and/or t(4;14) translocation, noted Lonial. In addition, overall PFS continued to improve after data cutoff in early November.

“The apparent maintenance of benefit over time speaks to the power of an immune-mediated approach to treating multiple myeloma,” he said.

Elotuzumab received Breakthrough Therapy status from the FDA last spring, based on phase II trial results. Currently, no monoclonal antibodies are approved for relapsed or refractory multiple myeloma.

“Based on this randomized phase III trial, we hope that we will soon have a new treatment option,” said Lonial. “An immune therapy–based approach can be added to lenalidomide/dexamethasone for the management of patients with relapsed or refractory multiple myeloma.”