Bristol-Myers Squibb
Elotuzumab Photo courtesy of
STOCKHOLM—Adding elotuzumab (E) to treatment with pomalidomide (P) and low-dose dexamethasone (d) can produce “clinically meaningful” results in patients with relapsed/refractory multiple myeloma (MM), according to an investigator for the ELOQUENT-3 trial.
In this phase 2 trial, patients who received EPd had double the overall response rate (ORR) and median progression-free survival (PFS) of patients who received Pd.
Additionally, adverse events (AEs) were comparable between the treatment arms.
Meletios Dimopoulos, MD, of National and Kapodistrian University of Athens in Greece, presented these results as a late-breaking abstract (LB2606) at the 23rd Congress of the European Hematology Association (EHA).
The research was sponsored by Bristol-Myers Squibb.
The ELOQUENT-3 trial enrolled MM patients who had refractory or relapsed and refractory MM. They had to have received lenalidomide and a proteasome inhibitor (PI).
The patients were randomized to receive EPd (n=60) or Pd (n=57) in 28-day cycles until disease progression or unacceptable toxicity.
Pomalidomide was given orally at 4 mg on days 1 to 21 of each cycle. In the Pd arm, dexamethasone was given as a 20 mg (for patients older than 75) or 40 mg (75 and younger) tablet weekly.
In the EPd arm, dexamethasone was split between oral (8 mg, 20 mg, or 40 mg tablets) and intravenous doses (8 mg or 28 mg).
Elotuzumab was given at 10 mg/kg intravenously weekly for the first 2 cycles and 20 mg/kg monthly from cycle 3 on.
Patient characteristics
The patients’ median age was 69 (range, 43-81) in the EPd arm and 66 (range, 36-81) in the Pd arm. They were a median of 4.8 years (EPd) or 4.4 years (Pd) from diagnosis.
The median number of prior therapies was 3 (range, 2-8) in both groups.
Ninety percent of patients in the EPd arm and 84% of those in the Pd arm were refractory to lenalidomide. Seventy-eight percent and 82%, respectively, were refractory to a PI. And 68% and 72%, respectively, were refractory to both lenalidomide and a PI.
Treatment duration
Dr Dimopoulos noted that twice as many patients remained on treatment with EPd compared to Pd at the time of database lock (February 21, 2018). Forty percent of EPd patients (n=24) and 20% of Pd patients (n=11) were still on treatment at that time.
Patients’ primary reason for treatment discontinuation was disease progression—43% of EPd recipients and 56% of Pd recipients. Two percent of EPd recipients and 4% of Pd recipients withdrew due to treatment-related toxicity. Four percent of patients in the Pd arm (and none in the EPd arm) withdrew due to maximum clinical benefit.
The median number of treatment cycles was 9 (range, 4-13) in the EPd arm and 5 (range, 3-10) in the Pd arm.
Efficacy
The ORR was 53% in the EPd arm and 26% in the Pd arm. The odds ratio was 3.25 (P=0.0029).
Eight percent of patients in the EPd arm had a complete response or stringent complete response, as did 2% of patients in the Pd arm.
The median duration of response was 8.3 months in the Pd arm and has not been reached in the EPd arm.
“Elotuzumab with pomalidomide and dexamethasone showed a significant and clinically meaningful 46% reduction in the risk of progression or death,” Dr Dimopoulos said.
The median PFS was 10.3 months with EPd and 4.7 months with Pd (hazard ratio=0.54, P=0.0078).
Although overall survival data are not yet mature, there was a trend favoring EPd over Pd (hazard ratio=0.62). There were 13 deaths in the EPd arm and 18 deaths in the Pd arm.
Safety
Dr Dimopoulos said AEs were comparable between the treatment arms. He pointed out that neutropenia was less common with EPd compared to Pd, despite similar pomalidomide dose intensity. And exposure-adjusted hematologic AEs and infections were lower with EPd than with Pd.
Ninety-seven percent of patients in the EPd arm and 95% in the Pd arm had at least 1 AE.
Grade 3-4 nonhematologic AEs (in the EPd and Pd arms, respectively) included constipation (2% and 0%), hyperglycemia (8% and 7%), bone pain (3% and 0%), dyspnea (3% and 2%), fatigue (0% and 4%), respiratory tract infection (0% and 2%), and upper respiratory tract infection (0% and 2%).
Grade 3-4 hematologic AEs (in the EPd and Pd arms, respectively) included anemia (10% and 20%), neutropenia (13% and 27%), thrombocytopenia (8% and 5%), and lymphopenia (8% and 2%).
Grade 3-4 AEs of special interest (in the EPd and Pd arms, respectively) included infections (13% and 22%), vascular disorders (3% and 0%), cardiac disorders (7% and 4%), and neoplasms (2% and 11%).
There were 5 grade 5 AEs in the EPd arm and 8 in the Pd arm.
In the EPd arm, grade 5 AEs included infection (n=3), cardiac failure, and general physical health deterioration.
In the Pd arm, grade 5 AEs included malignant neoplasm progression (n=4), infection, multiple organ failure and infection, myocardial infarction, and plasma cell myeloma.