Michael Giordano, MD
The FDA has granted elotuzumab (Empliciti) a priority review for use in combination therapy in patients with multiple myeloma following the failure of one or more prior therapies, according to Bristol-Myers Squibb and AbbVie, the co-developers of the drug.
A separate regulatory filing for the same indication was accepted and given an accelerated review by the European Medicines Agency (EMA) in late July. The FDA and EMA reviews will both be based primarily on data from the phase III ELOQUENT-2 trial, with supporting data coming from the phase II study CA204-009.
“Bristol-Myers Squibb is delighted by the approach both agencies have taken to review the Empliciti applications as it underscores the unmet medical need in the treatment of multiple myeloma and the role Immuno-Oncology may play,” Michael Giordano, MD, senior vice president, head of Oncology Development, Bristol-Myers Squibb, said in a statement. “The acceptance of our applications by the FDA and EMA brings Bristol-Myers Squibb’s Immuno-Oncology science a step closer to helping patients with hematologic malignancies.”
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 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 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 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 (range, 1-3) including bortezomib (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 (hazard ratio [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%.
Sagar Lonial, MD
“What I think is quite striking about this progression-free survival curve...is that the two curves do not appear to come back together with longer follow-up,” lead author Sagar Lonial, MD, said when discussing the results during a presscast held in advance of the ASCO 2015 Annual Meeting.
“This idea of the maintenance of benefit over time really speaks to the power of an immune-mediated based approach when we treat cancer. We’ve seen this, for instance, with PD-1 and other immune-based approaches,” added Lonial, who is chief medical officer of the Winship Cancer Institute of Emory University, and professor and executive vice chair of the Department of Hematology and Medical Oncology of Emory University School of Medicine.
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
= .0002). The OS data for the trial are not yet mature.
Elotuzumab was well-tolerated overall, according to Lonial. “The improvement in clinical parameters occurred without a significant increase in adverse events or toxicities. In fact, there was no reduction in quality of life for the group receiving the three drugs.”