FDA Approves New Multiple Myeloma Combination Therapy

Empliciti combination decreased disease progression risk by 30%.

A new treatment option will soon be available to patients with multiple myeloma who failed on prior treatment.

The FDA today approved elotuzumab (Empliciti) to be used in combination therapy to treat patients with multiple myeloma following failure on 1 to 3 prior therapies.

The approval followed the phase 3 ELOQUENT-2 trial, which found the addition of Empliciti to standard lenalidomide and dexamethasone treatment decreased disease progression risk by 30%.

“We are continuing to learn about the ways the immune system interacts with different types of cancer, including multiple myeloma," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research. “Today’s approval is the second monoclonal antibody approved to treat patients with multiple myeloma and works with another approved therapy to provide additional benefit.”

Today’s approval followed the approval earlier this month of daratumumab (Darzalex) a monoclonal antibody treatment for multiple myeloma.

Elotuzumab acts by binding to a protein on the surface of myeloma cells and natural killer lymphocytes in the immune system. The drug was granted breakthrough therapy designation in 2014 in combination with lenalidomide and dexamethasone for patients with multiple myeloma following 1 or more prior therapies.

The open-label trial randomized 646 patients with relapsed/refractory multiple myeloma administered lenalidomide and dexamethasone alone (n = 325) or in combination with elotuzumab (n = 321).

Elotuzumab was administered at 10 mg/kg IV weekly for the first 2 cycles and then every 2 weeks following, while lenalidomide was administered at 25 mg orally on days 1 to 21 of each cycle.

Patients were administered 40 mg of oral dexamethasone in weeks without elotuzumab across the trial. During weeks when patients received elotuzumab, dexamethasone was administered at 28 mg orally plus 8 mg IV. Across the trial, all 3-drug regimens were cycled at 28 days, with treatment administered until disease progression or unacceptable toxicity.

Patients in the trial had a median age of 66 years and had received a median of 2 prior therapies, including bortezomib (70%), thalidomide (48%), and lenalidomide (6%), with 35% of patients refractory to their most recent therapy. None of the patients were refractory to lenalidomide.

The primary outcome measures were progression-free survival (PFS) and overall response rate (ORR), with overall survival (OS) a secondary endpoint. Tumor response was assessed every 4 weeks, with survival assessed every 12 weeks following disease progression.

At a median follow-up of 2 years, PFS in the elotuzumab group was 19.4 months compared with 14.9 months in the lenalidomide and dexamethasone alone group. The 1-year PFS for the elotuzumab cohort was 68% compared with 57% in the control cohort. The difference in 2-year PFS rates increased to 41% with elotuzumab compared with 27% in the control group.

The ORR was 79% in the elotuzumab cohort compared with 66% for the control group, while OS data for was yet mature.

Thirty-five percent of patients in the elotuzumab group and 20% of patients in the lenalidomide and dexamethasone alone group remained on therapy.

The most common all-grade adverse events (AEs) in the elotuzumab group versus the control group were lymphocytopenia (99% vs 98%) anemia (96% vs 95%), thrombocytopenia (84% vs 78%), neutropenia (82% vs 89%), fatigue (47% vs 39%), diarrhea (47% vs 36%), and pyrexia (37% vs 25%).