Elotuzumab Approved by FDA for Patients With Multiple Myeloma

November 30, 2015
Jason M. Broderick

Elotuzumab (Empliciti) has been approved by the FDA for use in combination with lenalidomide (Revlimid) and dexamethasone in patients with multiple myeloma after the failure of at least 1 prior therapy.

Richard Pazdur, MD

Elotuzumab (Empliciti) has been approved by the FDA for use in combination with lenalidomide (Revlimid) and dexamethasone in patients with multiple myeloma after the failure of at least 1 prior therapy.

“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 approval was based on data from the phase III ELOQUENT-2 trial, in which the 3-drug elotuzumab combination reduced the risk of disease progression by 30% compared with lenalidomide/dexamethasone alone. The trial randomized 646 patients with relapsed/refractory multiple myeloma to 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 biweekly thereafter, and lenalidomide was dosed at 25 mg orally on days 1 to 21 of each cycle.

During the study, patients received 40 mg of oral dexamethasone in weeks without elotuzumab. In weeks when elotuzumab was administered in the experimental arm, 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 lenalidomide (6%). Thirty-five percent of patients were refractory to their most recent therapy; however, no patients were lenalidomide 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 elotuzumab regimen was 19.4 months (95% CI, 16.6-22.2) versus 14.9 months (95% CI, 12.1-17.2) with lenalidomide and dexamethasone alone (HR, 0.70; 95% CI, 0.57-0.85;P<.001). The 1-year PFS for the elotuzumab 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 elotuzumab 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 elotuzumab and 66% for the control group (P<.001). The OS data for the trial are not yet mature.

Elotuzumab was well tolerated overall. At the time of the interim analysis, 35% of patients receiving the elotuzumab regimen and 20% of patients receiving lenalidomide and dexamethasone alone remained on therapy. The most commonly reported all-grade adverse events (AEs) in the elotuzumab 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 elotuzumab versus control arms, respectively. Grade 3/4 lymphocytopenia rates were higher with elotuzumab 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 elotuzumab arm had infusion reactions, most of which were grade 1/2 (n = 29).

Elotuzumab 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 lenalidomide and dexamethasone for patients with multiple myeloma following one or more prior therapies.

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