Elotuzumab, a novel anti-SLAMF7 monoclonal antibody, extended multiple myeloma (MM) patients’ duration of remission by about five months, on average, compared with standard treatment alone, according to interim results of the phase III, randomized, open-label ELOQUENT-2 study presented at the 2015 American Society of Clinical Oncology Annual Meeting.1
ELOQUENT-2 is the largest study of a monoclonal antibody in multiple myeloma and the first phase III trial demonstrating benefit using a targeted immune-based approach to treating the disease.
“It appears that for patients with relapsed multiple myeloma who would otherwise be offered lenalidomide and dexamethasone, the addition of this new targeted drug makes the outcomes even better,” said lead study author and presenter Sagar Lonial, MD, professor and executive vice chair of the Department of Hematology and Medical Oncology of Emory University School of Medicine in Atlanta, Georgia.
The results were later published in The New England Journal of Medicine.2
In the analysis, Dr. Lonial and colleagues randomized 646 patients with relapsed/refractory MM to either ELO+LEN+DEX (n=321) or LEN+DEX (n=325). All patients were treated in 28-day cycles until disease progression or unacceptable toxicity.
Patients had been treated with one to three prior therapies, with a median of two prior therapies, which included bortezomib (70%), thalidomide (48%), and lenalidomide (6%). Notably, 35 percent were refractory to their last therapy, and 32 percent of patients had del17p.
At the data cut-off point, 35 percent of patients in the elotuzumab group and 21 percent of patients in the control group remained on therapy. Discontinuation of treatment was largely attributable to disease progression (42% in the ELO+LEN+DEX group and 47% in the LEN+DEX group).
Patients were followed for a median of 24 months, with an independent review committee monitoring and assessing treatment response and disease progression.
Focusing on the primary endpoints of progression-free survival (PFS) and overall response rate (ORR), treatment receiving the elotuzumab combination had a nearly five-month median increase in PFS over the control group (HR=0.70; 95% CI 0.57-0.85; p=0.0004; TABLE).
On the safety side, grade 3 or 4 adverse events (≥15%) in the ELO+LEN+DEX and LEN+DEX groups were neutropenia (25% vs. 33%) and anemia (15% vs. 16%). Exposure-adjusted infection rates were the same in both arms, and infusion reactions occurred in 10 percent of patients in the ELO group – most of which were grade 1 or 2 reactions. A total of 210 deaths occurred: 94 in the ELO+LEN+DEX group and 116 in the LEN+DEX group.
Importantly, Dr. Lonial noted, the PFS benefit was consistent across two key subgroups with high-risk genetic features: del17p and t[4;14]. These patients appeared to benefit from elotuzumab as much as patients with average risk.
“It was particularly striking that the difference between the elotuzumab and control groups seems to get bigger over time, which really speaks to the power of this immune-based approach,” Dr. Lonial added.
- Lonial S, Dimopoulos MA, Palumbo A, et al. ELOQUENT-2: A phase III, randomized, open-label study of lenalidomide (Len)/dexamethasone (dex) with/without elotuzumab (Elo) in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Abstract #8508. Presented at the 2015 American Society of Clinical Oncology Annual Meeting; June 2, 2015; Chicago, IL.
- Lonial S, Dimopoulos MA, Palumbo A, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621-31.
|TABLE. Rates of Primary Endpoints among ELOQUENT-2 Participants|
|Elotuzumab + lenalidomide + dexamethasone (N=321)||Lenalidomide + dexamethasone (N=325)|
|Progression-free survival (PFS), months||19.4 (95% CI 16.6-22.2)||14.9 (95% CI 12.1-17.2)|
|One-year PFS||68% (95% CI 63-73)||57% (95% CI 51-62)|
|Two-year PFS||41% (95% CI 35-47)||27% (95% CI 22-33)|
|Overall response rate||79% (95% CI 74-83)||66% (95% CI 60-71)|