According to interim results of the phase III, randomized, open-label ELOQUENT-2 study, elotuzumab may offer a new treatment option for patients with relapsed multiple myeloma. Adding the immune-based therapy to standard lenalidomide and dexamethasone (ELO+LEN+DEX) extended the duration of remissions by about five months, on average, compared with standard treatment alone.
“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 Sagar Lonial, MD, 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 in Atlanta, Georgia. Dr. Lonial presented the study results at the American Society of Clinical Oncology annual meeting.
The monoclonocal antibody elotuzumab targets SLAMF7 and kills myeloma cells – with minimal effect on normal tissue. In 2014, the U.S. FDA granted a breakthrough therapy designation to elotuzumab in combination with LEN+DEX to treat patients with relapsed multiple myeloma, based on promising results from earlier-phase trials. 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.
In the study, Dr. Lonial and colleagues randomized 646 patients with relapsed/refractory multiple myeloma 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 del(17p).
At the data cut-off point on November 4, 2014, 35 percent of patients in the ELO+LEN+DEX cohort and 21 percent of patients in the control group remained on therapy. Discontinuation of treatment was mostly 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 survival [OS], treatment with the elotuzumab combination was associated with a nearly five-month median increase in PFS over the control group (HR=0.70 95% CI 0.57-0.85; p=0.0004):
- PFS: 19.4 (95% CI 16.6-22.2) vs. 14.9 (95% CI 12.1-17.2)
- One-year PFS: 68 percent vs. 57 percent
- Two-year PFS: 41 percent vs. 27 percent
Overall response rates were also higher in the ELO+LEN+DEX group: 79% (95% CI 74-83) versus 66% (95% CI 60-71; p=0.0002).
On the safety side, grade 3 to 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: del(17p) and t[4;14]. These patients appeared to benefit from elotuzumab as much as patients with average risk. Unfortunately, conventional therapies tend to be less effective in those high-risk patients, making ELO a welcome addition to their treatment options.
“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.
Ongoing clinical trials are exploring the possibility of incorporating elotuzumab into therapies for patients with newly diagnosed multiple myeloma and testing various combinations of elotuzumab and existing treatments.
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, Chicago, Illinois, June 2, 2015.