Elotuzumab, a First-in-Class Monoclonal Antibody Immunotherapy, Improves Outcomes in Patients with Multiple Myeloma

Immunotherapy

The addition of the novel monoclonal antibody elotuzumab to dexamethasone plus lenalidomide resulted in a 30% reduction in the risk for disease progression and death in patients with relapsed or refractory multiple myeloma.

These interim results from the ELOQUENT-2 phase 3 trial, the largest study of a monoclonal antibody in multiple myeloma, are the first positive findings for a targeted immunotherapy approach in a phase 3 clinical trial in patients with multiple myeloma. Further studies of elotuzumab are ongoing in myeloma, and the drug has received a breakthrough therapy designation from the FDA for patients who have received ?1 previous therapies for multiple myeloma.

“We are excited about the progression-free survival [PFS] results attributable to this novel first-in-class monoclonal antibody. Elotuzumab achieved a longer duration of remission, and improved overall response rates, without a significant increase in adverse events and no reduction in quality of life,� said lead investigator Sagar Lonial, MD, Chief Medical Officer, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA. “We hope elotuzu­mab will be the first immune approach to be added to the management of relapsed/refractory multiple myeloma.�

Lonial explained that the novel mechanism of action of elotuzumab contains a “double whammy� by attaching to a cell-surface protein called SLAMF7, which is found on multiple myeloma cells and natural killer cells. “Thus, it acts directly on the tumor itself and enhances the activity of natural killer cells to kill the tumor,� he said.

ELOQUENT-2 Phase 3 Trial

The study randomized 646 patients with relapsed or refractory multiple myeloma to standard therapy with lenalidomide and dexamethasone or to standard therapy plus elotuzumab. All patients had disease refractory to 1 to 3 previous therapies.

“These patients enrolled in the trial early in the treatment phase. They had failed initial therapies but not multiple therapies, so they do not represent end-stage truly refractory patients,� Lonial said.

At a median follow-up of 24 months, the PFS rates were 41% in the triple-therapy arm and 27% in the standard-therapy arm (P = .004). At 1 year, the PFS rates were 68% and 57%,
respectively.

The overall response rates were 79% and 66%, respectively (P = .002), representing an absolute difference of 13% at 24 months.

“It is striking that 2 curves for each treatment arm remain separated at 2 years, which speaks to the duration of response and the power of an immune approach as part of treatment of multiple myeloma,� Lonial said.

Of note, patients at high risk as a result of the 17p deletion or t(4;14) genetic abnormalities had a similar benefit from elotuzumab as patients with average risk. These patients typically have less benefit from conventional therapies, Lonial noted.

Overall, elotuzumab was well tolerated, with no significant increases in adverse events. Approximately 10% of the patients had a mild infusion reaction with the first few doses of the monoclonal antibody immunotherapy.

“This therapy is an innovative approach, one that combines the precision of a targeted, immune-based therapy with traditional myeloma therapy. The results are very encouraging, giving renewed hope to patients who have relapsed,� stated ASCO President-Elect Julie M. Vose, MD, MBA, Chief of the Division of Oncology/Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, who was not involved in this trial.

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