Bristol-Myers Squibb Company announced that the European Commission (EC) has approved Empliciti (elotuzumab) plus pomalidomide and low-dose dexamethasone (EPd) for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI), and have demonstrated disease progression on the last therapy. This approval is based on data from the ELOQUENT-3 trial in which EPd doubled both median progression-free survival (PFS) and overall response rate (ORR) among patients with relapsed and refractory multiple myeloma versus pomalidomide and low-dose dexamethasone (Pd) alone.
“Multiple myeloma is a frequently recurring disease and the chance it will return after initial treatment is a heavy burden for patients to carry,” said Fouad Namouni, M.D., head, Oncology Development, Bristol-Myers Squibb. “We are proud that the European Commission has again recognized the role of Empliciti in helping European patients with multiple myeloma by approving a second Empliciti-based regimen in the relapsed and refractory setting.”
EPd is the first triplet combination approved in Europe based on a randomized clinical trial using the standard of care, Pd, as a comparator. Results from ELOQUENT-3 demonstrated that the addition of Empliciti to Pd can significantly prolong survival without disease progression among heavily pretreated patients with multiple myeloma regardless of the number of prior therapies received. Investigator-assessed PFS, the study’s primary endpoint, was 10.25 months (95% CI: 5.59 to not estimable) among patients randomized to EPd compared with 4.67 months (95% CI: 2.83 to 7.16) among patients treated with Pd alone, indicating a 46% reduction in risk of disease progression (HR 0.54; 95% CI: 0.34 to 0.86; p=0.0078) between EPd and Pd arms after a minimum follow-up of 9.1 months. A secondary endpoint of the study, ORR, was 53.3% (95% CI: 40.0 to 66.3) compared with 26.3% (95% CI: 15.5 to 39.7; p=0.0029) among patients receiving EPd or Pd, respectively.
“The approval of this elotuzumab-based triplet combination in the relapsed and refractory setting gives patients, and their doctors, a treatment alternative shown to have the potential to offer patients more time living without disease progression, coupled with a tolerable safety profile,” said Meletios A. Dimopoulos, M.D., professor and chairman of the Department of Clinical Therapeutics at National and Kapodistrian University of Athens.
Data from the ELOQUENT-3 trial were first presented at the 23rd Congress of the European Hematology Association (EHA) in 2018. Updated efficacy results with a minimum follow-up of 18.3 months were presented at the 24th Congress of the EHA this year. In this exploratory analysis, a total of 40 (67%) patients were alive in the EPd arm and 29 (51%) patients were alive in the Pd arm (HR 0.54; 95% CI: 0.30 to 0.96). Median OS was not reached for the EPd treatment arm.
Treatment-related Grade 3-4 adverse events (AEs) were comparable between EPd and Pd groups. Any-grade infections occurred in 65% of patients in both arms. Rates of the most commonly occurring Grade 3-4 hematologic AEs, neutropenia and anemia, were 13% and 10%, respectively, for patients receiving EPd and 27% and 20%, respectively, for patients receiving Pd, despite longer exposure within the EPd arm and similar dose intensity of pomalidomide between arms. AEs led to discontinuation in 18% of patients in the EPd arm, compared with 24% of patients in the Pd arm.
The U.S. Food and Drug Administration (FDA) approved EPd for the treatment of adult patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a PI, in November 2018.
Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.