Elotuzumab/Pomalidomide Prolongs PFS in Pretreated Multiple Myeloma

Meletios A. Dimopoulos, MD

The addition of elotuzumab (Empliciti) to pomalidomide (Pomalyst) and dexamethasone cut the risk of disease progression or death by 46% compared with pomalidomide and dexamethasone alone for patients with relapsed/refractory multiple myeloma, according to findings from the phase II ELOQUENT-3 trial reported at the 2018 EHA Congress.

Median progression-free survival (PFS) was 10.3 months (95% CI, 5.6-not evaluable) with the elotuzumab combination compared with 4.7 months (95% CI, 2.8-7.2) with pomalidomide plus dexamethasone (HR, 0.54; 95% CI, 0.34-0.86; P = .0078). The objective response rate (ORR) was 53% (95% CI, 40%-66%) with elotuzumab compared with 26% (95% CI, 16%-40%) in the control arm (odds ratio, 3.25; 95% CI, 1.49-7.11; P = .0029). The rate of very good partial response or better was 20% versus 9%, with and without elotuzumab, respectively.

“ELOQUENT-3 is the first randomized trial comparing the standard of care, pomalidomide and low-dose dexamethasone, with and without the addition of a monoclonal antibody,” said lead author Meletios A. Dimopoulos, MD, professor and chair of the Department of Clinical Therapeutics at the National Kapodistrian University of Athens in Athens, Greece. “These data support the hypothesis that the addition of elotuzumab to pomalidomide and dexamethasone elicits a synergistic effect and significantly prolongs the PFS of heavily pretreated patients with myeloma, regardless of the number of prior therapies.”

The phase II ELOQUENT-3 study enrolled 117 patients with relapsed/refractory multiple myeloma who were randomized to the elotuzumab combination (n = 60) or pomalidomide and dexamethasone alone (n = 57). Elotuzumab was administered at 10 mg/kg intravenously each week during cycles 1 and 2 and at 20 mg/kg every 4 weeks thereafter. Pomalidomide was given at 4 mg orally on days 1 to 21 of each cycle plus dexamethasone weekly at 40 mg for patients ≤75 years of age or 20 mg for those >75 years.

Eligible patients had received ≥2 prior lines of therapy, including lenalidomide and a proteasome inhibitor (PI); patients receiving prior pomalidomide were excluded from the study. The median age of patients was 67 years and they had received a median of 3 prior treatments (range, 2-8). Prior treatments included bortezomib (100%), lenalidomide (99%), carfilzomib (21%), ixazomib (6%), and daratumumab (3%). More than half of patients (55%) had undergone stem cell transplantation and most patients were refractory to lenalidomide (87%), a PI (80%), or both (70%).

The primary objective of the study was investigator-assessed PFS and secondary endpoints included ORR and overall survival (OS). At the February 21, 2018, database lock, the median follow-up was 9.1 months, and 40% of patients receiving the elotuzumab combination remained on treatment compared with 20% in the control arm.

Although OS results remained immature they suggested a trend favoring elotuzumab. At the analysis, there was a 38% reduction in the risk of death in the elotuzumab arm compared with the control group (HR, 0.62; 95% CI, 0.30-1.28). At the data cutoff, there were 13 deaths in the elotuzumab arm and 18 in the control arm.

Disease progression was the main cause of treatment discontinuation and occurred in 43% of patients in the elotuzumab arm compared with 56% in the control group. Discontinuation due to adverse events (AEs) occurred in 18% of patients in the elotuzumab arm compared with 24% for the control group.

The rates of grade 3/4 neutropenia and anemia were lower with elotuzumab versus the control arm, despite longer exposure (median number of cycles 9 versus 5). Pomalidomide dose intensity was similar between groups. Grade 3/4 neutropenia was experienced by 13% of patients in the elotuzumab group compared with 27% for the control arm and grade 3/4 anemia occurred in 10% versus 20% of patients, respectively. All-grade infections occurred in 65% of patients in both treatment arms. Five percent of patients in the elotuzumab group experienced infusion reactions that were grade 1/2 in severity.

“At the cutoff date, more patients remained on elotuzumab versus pomalidomide, and patients on elotuzumab demonstrated improved PFS and response rates. We believe that elotuzumab, if approved by regulatory authorities, could be an important treatment option for patients with relapsed or refractory multiple myeloma whose disease has progressed after lenalidomide or a proteasome inhibitor,” said Dimopoulos.

In the United States, elotuzumab was initially approved in November 2015 in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who received 1 to 3 prior therapies. In May 2016, elotuzumab was also approved by the European Commission in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma following progression on 1 prior therapy.

Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus pomalidomide/dexamethasone (EPd) vs Pd for treatment of relapsed/refractory multiple myeloma (RRMM): results from the phase 2, randomized open-label ELOQUENT-3 study. Presented at: 2018 EHA Congress; June 14-17, 2018; Stockholm, Sweden. Abstract LB2606.

<<< 2018 European Hematology Association Congress

Elotuzumab is an immunostimulary monoclonal antibody that specifically targets the signalling lymphocyte activation molecule family member 7 (SLAMF7), which is expressed as a surface protein on myeloma cells, natural killer (NK), and plasma cells. Elotuzumab has a dual mechanism of action to directly stimulate the immune system via NK activation and to directly target SLAMF7 on myeloma cells for activated NK destruction via ADCC toxicity.