Patients with previously treated multiple myeloma responded well to therapy with the monoclonal antibody elotuzumab in combination with lenalidomide and low-dose dexamethasone, with a high objective response rate and longer progression-free survival (PFS) in those who received the dose being taken into phase III studies.
The data from the small, randomized, open-label phase II study were jointly announced by Bristol-Myers Squibb and AbbVie and were also presented June 15 at the 18th Annual Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
Elotuzumab is a humanized monoclonal antibody that targets a cell-surface protein called CS1 that is highly expressed on multiple myeloma cells. The drug is able to induce cell breakdown and death in certain cancerous cells.
In this study, 73 patients with relapsed or refractory multiple myeloma were randomized 1:1 to receive elotuzumab in a dose of either 10 mg/kg or 20 mg/kg (intravenous infusion on days 1, 8, 15, and 22 of a 28-day cycle for two cycles and then on days 1 and 15 of any remaining cycles) in combination with lenalidomide 25 mg once daily on days 1 through 21 and dexamethasone 40 mg once weekly. Patients received treatment until their disease progressed or they experienced unacceptable toxicity. The primary endpoint of the study was objective response rate (ORR), with progression-free survival (PFS) and safety as secondary endpoints.
Among the patients who received the 10 mg/kg dose of elotuzumab (n=36), the median PFS was 33 months after a median follow-up of 20.8 months (95% CI, 14.9 – NA), with an ORR of 92%, the companies reported. This is the dose that will be used in ongoing phase III trials with elotuzumab. The median PFS was 18 months in the 20 mg/kg arm of the study (n=37) after a median follow-up of 17.1 months (95% CI, 12.912 – 32.361), and the ORR was 76%.
According to the companies, the safety data were consistent with previously reported results from this trial. Most treatment-emergent adverse events occurred within 18 months of initiating therapy; the most common grade 3 or 4 adverse events for the 10 mg/kg and 20 mg/kg arms, respectively, were lymphopenia (26% and 9%), neutropenia (21% and 22%), thrombocytopenia (21% and 17%), anemia (13% and 12%), leukopenia (8% and 7%), hyperglycemia (5% and 12%), pneumonia (8% and 5%), diarrhea (10% and 5 %), fatigue (8% and 9%), and hypokalemia (8% and 5%). Two patients died during the study, as was previously reported at the 2012 Annual Meeting and Exposition of the American Society of Hematology.
“There remains a high unmet medical need for patients with multiple myeloma, the second most common blood cancer, as many may relapse and stop responding to currently available treatments,” said Thierry Facon, MD, professor of Hematology in the Service des Maladies du Sang at the University of Lille in France, and lead investigator in the study, in a statement. “The phase II data on elotuzumab are encouraging and support further evaluation in phase III trials.”
The combination of elotuzumab with lenalidomide and low-dose dexamethasone is being further studied in two phase III trials. In the ELOQUENT-1 trial (NCT01335399), patients with previously untreated multiple myeloma will receive lenalidomide and low-dose dexamethasone with or without elotuzumab. The ELOQUENT-2 trial (NCT01239797) will investigate its use in relapsed or refractory disease patients.