Elotuzumab boosts response in relapsed, refractory multiple myeloma

By Shreeya Nanda, Senior medwireNews Reporter

Addition of the immunostimulatory antibody elotuzumab to the combination of lenalidomide and dexamethasone improves progression-free survival (PFS) and the overall response rate (ORR) in patients with relapsed or refractory multiple myeloma, research suggests.

Elotuzumab targets signalling lymphocytic activation molecule F7 (SLAMF), a glycoprotein expressed on myeloma but not healthy cells, explain the researchers, adding that the findings show that “direct activation and engagement of the innate immune system to selectively kill myeloma cells can provide clinically meaningful and statistically significant improvements in treatment outcomes.”

Of the 646 multiple myeloma patients with relapsed or refractory disease enrolled in the ELOQUENT-2 phase III trial, 321 received elotuzumab in addition to lenalidomide and dexamethasone while the remaining 325 were given lenalidomide and dexamethasone alone.

After a median follow-up of 24.5 months, median PFS was 19.4 months in the elotuzumab group and 14.9 months in the control group, a statistically significant difference, with a hazard ratio for progression or death of 0.70.

For patients in the elotuzumab group, the 1- and 2-year PFS rates were 68% and 41%, respectively – these compared with rates of 57% and 27% in the control patients.

The PFS benefit accorded by addition of elotuzumab remained consistent across various subgroups, including patients aged 65 years or older, those previously treated with bortezomib or immunomodulatory agents and those with a high-risk cytogenetic profile.

The ORR was also significantly higher in the elotuzumab than in the control treatment arm, at 79% versus 66%. But fewer patients in the elotuzumab group achieved a complete response compared with the control group (4 and 7%, respectively).

Pain severity and health-related quality of life were not significantly adversely affected by the addition of elotuzumab to lenalidomide and dexamethasone, “despite being a three-drug regimen that included an intravenous drug and a premedication regimen”, note Sagar Lonial, from Emory University School of Medicine in Atlanta, Georgia, USA, and co-authors.

Overall, serious adverse events occurred in 65% of patients in the elotuzumab treatment arm and 57% of those given the control therapy.

Lymphocytopenia was the most common haematological adverse event of grade 3 or 4 in either group, occurring in 77% and 49% of patients in the elotuzumab and control groups, respectively. And neutropenia was the second most frequent, reported in 34% and 44% of patients, respectively.

The research, published in The New England Journal of Medicine, was reported simultaneously at the 2015 annual meeting of the American Society of Clinical Oncology, held in Chicago, Illinois.

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