Antonio Palumbo, MD
The European Commission approved elotuzumab (Empliciti) for use in combination with lenalidomide (Revlimid) and dexamethasone for patients with multiple myeloma following progression on at least 1 prior therapy.
The approval was based on data from the phase III ELOQUENT-2 trial, in which the elotuzumab combination had a 3-year progression-survival rate of 23% versus 15% compared with lenalidomide/dexamethasone alone. An interim overall survival (OS) analysis showed a non-statistically significant 23% reduction in the risk of death with the addition of elotuzumab (HR, 0.77; 95% CI, 0.61-0.97; P
= .0257). The final survival analysis is still pending, Bristol-Myers Squibb and Abbie, the codevelopers of elotuzumab, noted in a statement.
“As multiple myeloma is largely incurable and is often characterized by a cycle of remission and relapse, there is a critical need for new therapies for patients that work in unique and innovative ways,” Antonio Palumbo, MD, an investigator on ELOQUENT-2 and chief of the Myeloma Unit in the Department of Oncology at the University of Torino in Torino, Italy. “In clinical trials, Empliciti in combination with lenalidomide and dexamethasone delivered a significant benefit in progression-free survival compared to lenalidomide and dexamethasone alone, which could make a meaningful difference in the lives of patients struggling with this serious disease.”
The open-label phase III ELOQUENT-2 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. Across the study, patients received 40 mg of oral dexamethasone in weeks without elotuzumab. In weeks in the experimental arm when elotuzumab 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 2 prior 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). 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. The addition of elotuzumab to lenalidomide/dexamethasone reduced the risk of disease progression or death by 32% (HR, 0.68; 97.61% CI, 0.55-0.85; P = .0001).
The 1-year PFS rate for the elotuzumab versus control arm was 68% versus 56%, respectively, with the difference in 2-year PFS rates increasing to 39% versus 26%. 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 78.5% with elotuzumab and 65.5% for the control group (P = .0002). The median time to next therapy was 33.35 months versus 21.22 months, respectfully (HR, 0.62; 95% CI, 0.50-0.77).
The most frequently reported all-grade adverse events (AEs) in the elotuzumab arm versus the control arm were diarrhea (59.2% vs 49.3%), pyrexia (43.0% vs 27.7%), fatigue (40.0% vs 34.7%), cough (33.2% vs 20.3%), nasopharyngitis (29.5% vs 27.7%), upper respiratory tract infection (25.2% vs 22.7%), lymphopenia (17.6% vs 13.6%), headache (17.2% vs 9.6%), pneumonia (15.6% vs 12.9%) and herpes zoster (10.0% vs 5.7%). The most common grade 3/4 AEs in the treatment versus control arms were lymphopenia (12.7% vs 7.4%), pneumonia (10.5% vs 8.1%), fatigue (6.4% vs 6.2%), diarrhea (3.7% vs 3.1%) and deep vein thrombosis (3.5% vs 1.7%).
AE-related discontinuations occurred in 8.7% of the elotuzumab arm and 12.9% of the control arm. Infusion reactions, all of which were grade ≤3, were reported in 10% of patients in the elotuzumab arm. Infusion reactions caused discontinuations in 1% of patients.
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 approved elotuzumab in November 2015 for use in combination with lenalidomide (Revlimid) and dexamethasone for patients with multiple myeloma following the failure of 1 to 3 prior therapies.
“Empliciti represents an important new treatment option for patients with multiple myeloma and healthcare providers who are treating this cancer in Europe,” Michael Severino, MD, executive vice president of Research and Development and chief scientific officer at AbbVie, said in statement. “AbbVie is proud to be part of the team that developed Empliciti and pleased to be partnering with Bristol-Myers Squibb to bring this new therapy to previously treated multiple myeloma patients.”