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Elotuzumab combination extends PFS for certain patients with relapsed, refractory multiple myeloma
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The addition of the elotuzumab to pomalidomide and dexamethasone conferred a significant PFS benefit among certain patients with relapsed or refractory multiple myeloma, according to results of a randomized phase 2 trial published in The New England Journal of Medicine.
The combination also induced a higher overall response rate than pomalidomide and dexamethasone alone.
Elotuzumab (Empliciti; Bristol-Myers Squibb, AbbVie) is an immunostimulatory monoclonal antibody that binds to signaling lymphocytic activation molecule F7, a glycoprotein that is highly expressed on the surface of myeloma cells, natural killer cells and some immune cells but not on normal tissues.
“The combination of elotuzumab and pomalidomide [Pomalyst, Celgene] may have synergistic clinical effects in patients with multiple myeloma that relapsed after treatment with lenalidomide [Revlimid, Celgene] or is refractory to lenalidomide,” Meletios A. Dimopoulos, MD, professor and chairman of the department of clinical therapeutics at the National and Kapodistrian University of Athens School of Medicine, and colleagues wrote. “These clinical data confirm the findings of preclinical studies in mice, which showed that elotuzumab, pomalidomide and dexamethasone synergize to kill myeloma cells.”
The multicenter, open-label study included 117 patients with multiple myeloma. All patients had an ECOG performance score of 0 to 2.
Researchers assigned patients 1:1 to elotuzumab plus pomalidomide and dexamethasone (n = 60; median age, 69 years, 32% men) or pomalidomide and dexamethasone alone (n = 57; median age, 66 years, 35% men). Randomization was stratified according to number of previous lines of therapy and disease stage at time of enrollment.
Patients had undergone a median three prior therapies (range, 2-8), and 68% of patients in the elotuzumab group and 72% in the control group had multiple myeloma that was refractory to both lenalidomide and a proteasome inhibitor.
Investigator-assessed PFS — defined as the time from randomization to the first occurrence of disease progression or death from any cause — served as the primary endpoint. ORR and OS served as secondary endpoints.
Treatment was administered in 28-day cycles until disease progression, unacceptable toxicity or withdrawal of consent.
After minimum follow-up of 9.1 months, median PFS as assessed by independent review committee was 10.3 months (95% CI, 6.5-not reached) in the elotuzumab group and 4.7 months (95% CI, 2.8-7.6) in the control group (HR = 0.54; 95% CI, 0.34- 0.86).
The ORR was 53% in the elotuzumab group and 26% in the control group (OR, 3.25; 95% CI, 1.49- 7.11).
Grade 3 or 4 adverse events occurred among 57% of patients in the elotuzumab group and 60% in the control group. The most common adverse events were neutropenia (13% vs. 27%), anemia (10% vs. 20%) and hyperglycemia (8% vs. 7%). Infections of any grade were reported among 65% of all patients.
Treatment was discontinued because of disease progression among 43% of the elotuzumab group and 56% of the control group.
“The results thus far are encouraging, but extended followup is warranted to determine longterm efficacy and safety outcomes, including the final analysis of overall survival,” Dimopoulos and colleagues wrote. – by John DeRosier
Reference:
Dimopoulos M, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1805762
Disclosure: This study was funded by Bristol-Myers Squibb and AbbVie. Dimopoulos reports honoraria from advisory board participation with Amgen, Bristol-Myers Squibb, Celgene, Janssen and Takeda. Please see the study for all authors’ relevant financial disclosures.