FDA Approves Empliciti in Combination for Multiple Myeloma

The FDA has approved Empliciti (elotuzumab) in combination with Revlimid (lenalidomide) and dexamethasone for patients with multiple myeloma who have received one to three prior therapies.

Richard Pazdur, MD

The FDA has approved Empliciti (elotuzumab) in combination with Revlimid (lenalidomide) and dexamethasone for patients with multiple myeloma who have received one to three prior therapies.

The approval was based on data from the phase III ELOQUENT-2 trial, in which adding Empliciti to standard Revlimid/dexamethasone reduced the risk of disease progression 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’s 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.” The FDA approved the monoclonal antibody daratumumab (Darzalex) for multiple myeloma earlier this month.

The open-label phase III ELOQUENT-2 trial randomized 646 patients with relapsed/refractory multiple myeloma to Revlimid and dexamethasone alone (n = 325) or in combination with Empliciti (n = 321). Empliciti was administered at 10 mg/kg IV weekly for the first 2 cycles and then biweekly thereafter, and Revlimid was dosed at 25 mg orally on days 1 to 21 of each cycle. Across the study, patients received 40 mg of oral dexamethasone in weeks without Empliciti. In weeks in the experimental arm when Empliciti was administered, dexamethasone was dosed at 28 mg orally plus 8 mg IV. The cycle length for all 3-drug regimens was 28 days, and treatment was administered until disease progression or unacceptable toxicity.

The median patient age in the trial was 66 years and patients had received a median of 2prior therapies (range, 1-3) including bortezomib (Velcade; 70%), thalidomide (48%), and Revlimid (6%). Thirty-five percent of patients were refractory to their most recent therapy; however, no patients were Revlimid refractory. High-risk patient subgroups were identified, with 32% and 9% of patients having a 17p deletion (del[17p]) or t(4;14) translocation, respectively.

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

At a median follow-up of 2 years, PFS with the Empliciti regimen was 19.4 months (95% CI, 16.6-22.2) versus 14.9 months (95% CI, 12.1-17.2) with Revlimid and dexamethasone alone (HR, 0.70; 95% CI, 0.57-0.85; P <.001). The 1-year PFS for the Empliciti versus control arm was 68% versus 57%, respectively, with the difference in 2-year PFS rates increasing to 41% versus 27%.

The PFS benefit with Empliciti in the overall study was observed across the high-risk del(17p) and t(4;14) subgroups, with HRs of 0.65 and 0.53, respectively.

ORR was 79% with Empliciti and 66% for the control group (P <.001). The OS data for the trial are not yet mature.

Empliciti was well tolerated overall. At the time of the interim analysis, 35% of patients receiving the elotuzumab regimen and 20% of patients receiving Revlimid and dexamethasone alone remained on therapy. The most commonly reported all-grade adverse events (AEs) in the Empliciti arm versus the control arm 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%).

Serious AEs occurred in 65% versus 57% of the Empliciti versus control arms, respectively. Grade 3/4 lymphocytopenia rates were higher with Empliciti at 77% versus 49%; however, high-grade neutropenia rates were higher in the control arm, at 44% versus 34%. Ten percent of patients (n = 33) in the Empliciti arm had infusion reactions, most of which were grade 1/2 (n = 29).

Empliciti binds to the SLAMF7 protein found on the surface of both myeloma cells and natural killer (NK) lymphocytes in the immune system. The FDA granted the drug a breakthrough therapy designation in May 2014 for use in combination with Revlimid and dexamethasone for patients with multiple myeloma following one or more prior therapies.

The ongoing phase III ELOQUENT-1 trial is examining Empliciti plus Revlimid and dexamethasone in the frontline setting for relapsed/refractory multiple myeloma. Other ongoing trials are examining Empliciti in various other combinations with existing therapies.