STOCKHOLM –Adding the monoclonal antibody elotuzumab to pomalidomide and dexamethasone nearly doubled the overall response rate and median progression-free survival in patients with relapsed/refractory multiple myeloma compared with pomalidomide and dexamethasone alone, results of the phase 2 ELOQUENT-3 trial showed.
After a minimum follow-up of 9.1 months, median progression-free survival (PFS) for 60 patients assigned to receive elotuzumab (Empliciti), pomalidomide (Pomalyst), and dexamethasone (EPd) was 10.3 months, compared with 4.7 months for 60 patients assigned to pomalidomide and dexamethasone (Pd). This difference translated into a hazard ratio (HR) of 0.54 (P = .0078) favoring EPd, reported Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens (Greece).
“The study met its primary endpoint, which was specifically designed to detect a large treatment effect in a relatively small sample of patients. Elotuzumab with pomalidomide and dexamethasone showed a significant and clinically meaningful 46% reduction in the risk of progression or death,” he said at the annual congress of the European Hematology Association.
Elotuzumab is an immunoglobulin G (IgG) monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7) expressed on multiple myeloma cells. Pomalidomide, an immunomodulator, may act synergistically with elotuzumab through several different mechanisms to increase killing of multiple myeloma cells, Dr. Dimopoulos said.
In ELOQUENT-3, patients with relapsed or refractory multiple myeloma after 2 or more prior lines of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor and no prior pomalidomide were enrolled and randomly assigned to receive either pomalidomide 4 mg orally on days 1-21 of each 28-day cycle plus oral dexamethasone 40 mg equivalent weekly, or to the same regimen plus intravenous elotuzumab 10 mg/kg weekly for cycles 1 and 2, and 20 mg/kg every 4 weeks for cycle 3 and subsequent cycles.
The trial met its primary endpoint of investigator-assessed PFS, with a 46% reduction in the risk of progression or death with EPd compared with Pd.
An analysis of PFS by subgroups showed that EPd was significantly superior to Pd for patients younger than 65 years, those with International Staging System stage I-II at study entry, patients with lactate dehydrogenase levels below 300 IU/L at baseline, patients who had two or three prior lines of therapy vs. four or more, and those who had disease that was refractory to both lenalidomide and a proteasome inhibitor.
EPd was also associated with a trend toward better PFS in an analysis combining patients with high-risk cytogenetics (deletion 17p or translocation 14;16) or high LDH levels, with a median of 7.7 months compared with 3.6 months for Pd. However, the HR, 0.55, was not statistically significant, likely because of the small sample size.
Similarly, the elotuzumab-containing combination showed a nonsignificant trend toward better PFS among patients without high risk disease, with a median PFS not reached, vs. not reached, vs. 4.7 months for patients treated with Pd.
The overall response rate with EPd was 53%, compared with 26% for Pd (odds ratio 3.5, P = .0029). The responses in the elotuzumab arm consisted of 8% complete response, 12% very good partial responses, and 33% partial responses. The respective rates in the Pd group were 2%, 7%, and 18%.
The median duration of response with EPd was not reached at the time of the database lock, compared with 8.3 months with Pd.
A preliminary analysis of overall survival showed a trend favoring EPd (13 deaths out to 22 months of follow-up, compared with 18 deaths out to 20 months in the Pd arm; HR 0.62, nonsignificant).
There were five treatment-related deaths in the EPd arm, and eight in the Pd arm. Grade 1 or 2 infusion reactions occurred in three patients in the EPd arm.
Other adverse events were comparable between the arms, with 57% of patients in the EPd arm and 60% in the Pd arm having at least one grade 3 or 4 adverse event.
“The hematologic toxicity was driven by pomalidomide and low-dose dexamethasone. For unclear reasons, there was less grade 3 or 4 neutropenia with the addition of elotuzumab to pomalidomide/dexamethasone, and also the infection rate was lower in the EPd arm,” Dr. Dimopoulos said.
SOURCE: Dimopoulos MA et al. EHA Congress, Abstract LB2606.