FDA Approves Empliciti for Multiple Myeloma

The FDA approved Empliciti (elotuzumab) for use in combination therapy in patients with multiple myeloma following the failure of one to three prior therapies.

The approval was based on data from the phase 3 ELOQUENT-2 trial, in which adding Empliciti to standard Revlimid (lenalidomide)/dexamethasone reduced the risk of disease progression by 30 percent.

“We are continuing to learn about the ways the immune system interacts with different types of cancer, including multiple myeloma," said Richard Pazdur, 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 Darzalex (daratumumab) for multiple myeloma earlier this month.

The open-label phase 3 ELOQUENT-2 trial randomized 646 patients with relapsed/refractory multiple myeloma to Revlimid and dexamethasone alone (325 patients) or in combination with Empliciti (321 patients). Empliciti was administered at 10 mg/kg IV weekly for the first two cycles and then biweekly thereafter, and lenalidomide 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 three-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 two prior therapies (ranging from one to three) including Velcade (bortezomib; 70 percent), thalidomide (48 percent), and Revlimid (6 percent). 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 percent and 9 percent 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 four weeks and survival was assessed every 12 weeks following disease progression.

At a median follow-up of two years, PFS with the Empliciti regimen was 19.4 months versus 14.9 months with Revlimid and dexamethasone alone. The one-year PFS for the Empliciti versus control arm was 68 percent versus 57 percent, respectively, with the difference in two-year PFS rates increasing to 41 percent versus 27%.

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

ORR was 79 percent with Empliciti and 66 percent for the control group. The OS data for the trial are not yet mature.

Empliciti was well tolerated overall. At the time of the interim analysis, 35 percent of patients receiving the Empliciti regimen and 20 percent 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 percent vs 98 percent) anemia (96 percent vs 95 percent), thrombocytopenia (84 percent vs 78 percent), neutropenia (82 percent vs 89 percent), fatigue (47 percent vs 39 percent), diarrhea (47 percent vs 36 percent) and pyrexia (37 percent vs 25 percent).

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

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 3 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.