Elotuzumab Effective, Safe for Relapsed, Refractory Myeloma

November 27, 2015

Adding elotuzumab to lenalidomide and dexamethasone for the treatment of relapsed or refractory multiple myeloma appears to result in better efficacy and safety.

Adding elotuzumab, a humanized monoclonal antibody targeting SLAMF7, to lenalidomide and dexamethasone for the treatment of relapsed or refractory multiple myeloma resulted in efficacy and safety that seems better than that previously reported with lenalidomide and dexamethasone alone, according to the results of the phase II Study 1703 published in Lancet Haematology.

“Elotuzumab, a novel immunotherapeutic antibody, shows clinical efficacy in patients with relapsed multiple myeloma at both 10 mg/kg and 20 mg/kg doses in combination with lenalidomide and dexamethasone, possibly due to activation of the innate immune system to selectively kill myeloma cells,” wrote researchers led by Paul G. Richardson, MD, of Dana-Farber Cancer Institute in Boston. “This combination provided clinically meaningful benefit in these patients, as measured by the proportion of patients who achieved an overall response, with more than half of patients showing a high-quality response.”

The phase II study randomly assigned 73 patients to elotuzumab 10 mg/kg (n = 73) or 20 mg/kg (n = 37) combined with lenalidomide and dexamethasone. The primary endpoint of the study was the proportion of patients who achieved an objective response.

At the data cutoff, 84% of patients had achieved an objective response: 92% with the 10 mg/kg dose and 76% with the 20 mg/kg dose. Forty-two percent of patients had a very good partial response (47% with the 10 mg/kg dose and 38% with the 20 mg/kg dose) and 27% had a partial response (28% with the 10 mg/kg dose and 27% with the 20 mg/kg dose). The researchers noted that the trial was not designed to detect differences between the 10 mg/kg and 20 mg/kg dosages.

“Tolerability was generally equivalent between the two doses, with similar occurrences and severity of adverse events, serious adverse events, and infusion reactions,” the researchers wrote.

Seventy-eight percent of patients experienced grade 3 or 4 adverse events. The most common grade 3 or 4 events were lymphopenia (21%) and neutropenia (19%). No treatment-related deaths occurred in either dosage group.

Based on these results, Richardson and colleagues concluded that elotuzumab “has the potential to be an important addition to the multiple myeloma treatment arsenal, for which alternative options with differing mechanisms of action, and the ability to complement existing combination strategies, are urgently needed.”

In September, elotuzumab was granted US Food and Drug Administration priority review based on data from the ELOQUENT-2 trial, a phase III study that looked at elotuzumab combined with lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone. The trial showed that patients with refractory or relapsed multiple myeloma who were treated with the elotuzumab combination had significantly greater reductions in risk for disease progression or death.  

In an editorial that accompanied the results by Richardson and colleagues, Antonio Palumbo, MD, of the University of Torino, Italy, wrote: “The results of the phase Ib/II study, and particularly those of the ELOQUENT-2 study, suggest that the combination of elotuzumab plus lenalidomide/dexamethasone could be one of the new standards of care for patients with relapsed or refractory multiple myeloma, with no additional toxic effects. Longer follow-up is needed to assess whether a subgroup of patients might have a very prolonged duration of remission. Additionally, further evidence is needed to support the role of treatment strategies that combine cytoreduction and tumor immunosurveillance for multiple myeloma, as already used for other tumors.”