Results from the phase II ELOQUENT-3 trial demonstrate that the combination of elotuzumab plus pomalidomide and dexamethasone extended progression-free survival (PFS) compared with pomalidomide and dexamethasone alone in patients with multiple myeloma (MM) that was refractory and/or relapsed following treatment with lenalidomide and a proteasome inhibitor (PI). The findings, which were published in the New England Journal of Medicine, also confirm the previously reported safety profile of this three-drug regimen, suggesting that the approach could represent an alternative triplet regimen for patients with lenalidomide-refractory disease.
In ELOQUENT-3, Meletios A. Dimopoulos, MD, of National and Kapodistrian University of Athens in Greece, and co-authors evaluated the safety and efficacy of elotuzumab plus pomalidomide and dexamethasone, compared with pomalidomide and dexamethasone alone in 117 patients with previously treated MM. Patients were enrolled from March 2016 through April 2017 at 43 sites in Europe, North America, Japan, and Australia.
All participants had received at least two prior therapies and had disease that was considered refractory to PI, lenalidomide, and the most recent treatment; patients with relapsed and refractory disease must have achieved at least a partial response (PR) to previous treatment with PI or lenalidomide or both but must also have had disease that progressed within six months and was refractory to last treatment.
After randomization by number of previous lines of therapy (2-3 or ≥4) and International Staging System disease stage at enrollment:
- 57 patients received pomalidomide (4 mg/day on days 1-21 of each cycle) plus dexamethasone (40 mg/week for patients ≤75 years or 20 mg/week for patients >75 years)
- 60 patients received pomalidomide and dexamethasone plus elotuzumab (10 mg/kg on days 1, 8, 15, and 22 during cycles 1-2 and 20 mg/kg on day 1 of each cycle thereafter)
Treatment was given in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent.
“The characteristics of the two treatment groups were generally well balanced at baseline,” the researchers noted, with a median of three previous lines of therapy (range = 2-8) in both groups. “In all, 68 percent of the patients in the elotuzumab group and 72 percent in the control group had MM that was refractory to both lenalidomide and a PI.”
At the time of data cutoff (February 2018), patients were followed for a minimum of 9.1 months. During the follow-up period, 40 percent of elotuzumab-treated patients and 20 percent of the control group were continuing to receive their assigned treatment.
Disease progression was the most common cause for treatment discontinuation (43% of elotuzumab-treated patients and 56% of control patients). Overall, patients received a median of nine treatment cycles (interquartile range [IQR] = 4-13) in the elotuzumab group and five (IQR = 3-10) in the control group.
Median PFS, per investigator assessment (primary endpoint), was significantly longer in the elotuzumab group (10.3 months [range = 5.6 months to not reached] vs. 4.7 months [range = 2.8-7.2 months]), which represented a 46-percent lower risk of disease progression or death with elotuzumab (hazard ratio [HR] = 0.54; 95% CI 0.34-0.86; p=0.008).
Elotuzumab also appeared to increase overall response rates (defined as ≥PR) compared with the control group (53% vs. 26%; p value not reported). The median duration of response was not reached (range = 8.3 months to not reached) in the elotuzumab group and was 8.3 months (range = 4.6 to not reached) in the control group. See the TABLE for all response data.
Overall survival data were immature at the time of the analysis, though the authors noted a signal “favoring the elotuzumab group was observed (HR=0.62; 95% CI 0.30-1.28; p value not reported).”
During study follow-up, 13 patients (22%) in the elotuzumab group and 18 (32%) in the control group died, mainly due to disease progression. None of these deaths were considered related to the study drug.
The most common any-grade adverse events (AEs; reported in ≥15% of patients) included:
- infections (65% with elotuzumab and 65% with control)
- anemia (25% and 36%)
- neutropenia (23% and 31%)
- constipation (22% and 11%)
- hyperglycemia (20% and 15%)
- diarrhea (18% and 9%)
- thrombocytopenia (15% and 18%)
Grade 3 or 4 AEs were reported in 57 percent of the patients in the elotuzumab group and in 60 percent in the control group, the most common of which were hematologic AEs (neutropenia, 13% and 27%; anemia, 10% and 20%). Serious AEs occurred at a similar rate (53% and 55% in the elotuzumab and control groups, respectively). This included one patient who developed a second primary cancer in one patient.
Overall, the toxicity profile with this elotuzumab-based regimen was consistent with that reported with other elotuzumab- and pomalidomide-containing regimens.
The efficacy and safety outcomes observed in this trial suggest that elotuzumab plus pomalidomide and dexamethasone represents an alternative treatment option to other pomalidomide and dexamethasone–based regimens. “However, caution is warranted when comparing results across trials,” the authors concluded.
The findings of ELOQUENT-3 are limited by the small patient population, and extended follow-up is warranted to determine long-term efficacy and safety outcomes, including the final analysis of overall survival. Future trials also are needed to compare outcomes between elotuzumab regimens containing lenalidomide or pomalidomide.
The authors report relationships with Bristol-Myers Squibb and AbbVie, which sponsored the trial.
Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med. 2018;379:1811-22.