A collaboration between Bristol-Myers Squibb and AbbVie Biotherapeutics is making possible a Phase 3 clinical study to treat patients with refractory multiple myeloma. The treatment, lenalidomide and dexamethasone with elotuzumab, has so far shown excellent safety and efficacy data in Phase 1b-2 studies, giving new hope to patients who otherwise have only a five-year overall survival rate.
“Combination therapy may be key to overcoming drug resistance and improving long-term treatment outcomes,” explained Sagar Lonial, MD, lead author of a paper to describe the methods of the ongoing Phase 3 trial. Current treatments, including lenalidomide with dexamethasone, generally use proteasome inhibitors and immunomodulatory drugs, but patients often relapse on these treatments. The researchers at Bristol-Myers Squibb and AbbVie believe adding the first-in-class humanized immunoglobulin G1 immunostimulatory monoclonal antibody, otherwise known as elotuzumab, will enhance the efficacy of lenalidomide and dexamethasone.
As a monoclonal antibody, elotuzumab specifically targets the signaling lymphocytic activation molecule F7 (SLAMF7) on the surface of myeloma cells. Healthy cells do not express SLAMF7, making elotuzumab an excellent candidate for mediating myeloma cell destruction by stimulating the immune system against myeloma cells.
Explained thoroughly in the article, “Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma,” which was published in the journal The New England Journal of Medicine, the group’s clinical study, “Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma (ELOQUENT – 2),” will continue to test the safety and efficacy of adding elotuzumab to patients’ treatment regimens. Over 600 patients are enrolled in the study, which is estimated to be completed in May 2016 for primary outcome measures.
During the study, patients are treated with lenalidomide, dexamethasone, and elotuzumab or with only lenalidomide and dexamethasone. Since elotuzumab is a protein, it is administered via IV injection, while lenalidomide and dexamethasone are available in oral formulations. Interim analysis of progression-free survival (a co-primary endpoint) showed a higher percentage of surviving patients in the elotuzumab group than the non-elotuzumab group after one and two years of treatment. Similarly, the length of progression-free survival was greater in the elotuzumab group.
“Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death,” explained Dr. Lonial. Considering the low rates of survival, this new therapeutic treatment may greatly improve the lives of multiple myeloma patients.