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Adding the monoclonal antibody elotuzumab (Empliciti) to lenalidomide (Revlimid) and dexamethasone failed to improve outcomes for patients with newly diagnosed, transplant-ineligible multiple myeloma, a phase III trial showed.

The so-called ELOQUENT-1 study failed to meet its primary endpoint. Over a median follow-up of 70.6 months, progression free survival (PFS) was 31.4 months with the elotuzumab-based combination versus 29.5 months with lenalidomide and dexamethasone alone (HR 0.93, 95.71% CI 0.77-1.12, P=0.44), reported Meletios Dimopoulos, MD, of the University of Athens School of Medicine in Greece, and colleagues.

PFS rates were comparable between the elotuzumab arm and control arm in years 1 to 4, and a similar 26% and 25%, respectively, at year 5. As for the study's other secondary endpoints, the overall response rates were 83% and 79% (P=0.22); and median overall survival was 60.4 months versus 57.6 months (P=0.89), they noted in

The results of this trial failed to replicate the positive results from ELOQUENT-2, which showed that elotuzumab plus lenalidomide and dexamethasone resulted in statistically significant improvements in PFS (19.4 months vs 14.9 months with lenalidomide and dexamethasone) and overall survival (48.3 months vs 39.6 months, respectively) in patients with relapsed multiple myeloma who received one to three previous lines of therapy.

In an , Cyrille Touzeau, MD, PhD, of University Hospital Hôtel-Dieu in Nantes, France, noted that there are no clear explanations for the contrasting results between the two trials, pointing out that similar results have been seen with other anti-myeloma agents. For example, the superiority of carfilzomib (Kyprolis) over bortezomib (Velcade) reported in the relapsed setting in the phase III was not seen in older patients with newly diagnosed multiple myeloma in the phase III and trials.

Thus, he observed, the combination of daratumumab (Darzalex) plus lenalidomide and dexamethasone, which improved PFS in the phase III MAIA trial, remains the gold standard of treatment for older patients with newly diagnosed disease.

A possible explanation for the contrasting results between the ELOQUENT trials could be "less favorable efficacy or safety in the older population characterized by higher frailty and comorbidities," Touzeau suggested. "Possibly the insufficient elotuzumab antitumor activity could also explain the negative results of ELOQUENT-1. As opposed to anti-CD38 monoclonal antibodies, elotuzumab does not induce substantial anti-myeloma activity as a single drug."

ELOQUENT-1 was conducted across 19 countries and included 748 patients (median age 73, 55% men, 95% white) with newly diagnosed, untreated, symptomatic multiple myeloma who were assigned 1:1 to receive either elotuzumab plus lenalidomide and dexamethasone or lenalidomide and dexamethasone alone from August 2011 to June 2014. All patients were ineligible for hematopoietic stem cell transplant due to advanced age or comorbidities.

The median time to response was 1.1 months in the elotuzumab group versus 1.9 months in the control group. Median time to best response was also similar between groups (5.6 months vs 4.7 months), as was median duration of response (33.2 months vs 33.1 months).

The most common grade 3/4 treatment-related adverse event was neutropenia (17% of the elotuzumab group vs 21% of the control group), while study drug toxicity was the reported cause of death in five patients and four patients, respectively.

Dimopoulos and colleagues noted that while disease progression was the main factor in treatment discontinuation for patients receiving lenalidomide and dexamethasone (38% vs 31% of the elotuzumab group), a greater proportion of patients in the elotuzumab group had adverse events leading to discontinuation (42% vs 35%).

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