Relapsed, Refractory Multiple Myeloma Progression Free Survival Prolonged with Drug Combo

Elotuzumab in combination with bortezomib and dexamethasone prolongs the progression free survival of patients with relapsed or refractory multiple myeloma (RRMM), according to the study “Randomized phase 2 study of elotuzumab plus bortezomib/dexamethasone (Bd) versus Bd for relapsed/refractory multiple myeloma,” recently published in Blood.

Current choices of care for the treatment of RRMM for new and current patients, include bortezomib in combination with dexamethasone (Bd), though a cure for the disease is currently available and patients eventually relapse or become drug resistant.

Immuno-oncology therapies hold potential for long-term survival benefits. Elotuzumab is an immunostimulatory monoclonal antibody that targets SLAMF7, a glycoprotein highly expressed in myeloma cells. The agent was approved in November, 2015 to be used in combination with lenalidomide and dexamethasone.

“Elotuzumab showed enhanced activity when combined with bortezomib in a preclinical myeloma model,” Dr. Andrzej Jakubowiak, PhD, professor of medicine and director of the myeloma program at The University of Chicago Medicine, and colleagues wrote according to a news release. “In a phase 1 dose-escalation safety study, IV elotuzumab plus bortezomib and dexamethasone was well tolerated in patients with relapsed or refractory multiple myeloma, with an overall response rate of 48% and median time to progression of 9.5 months, which suggests improved activity compared with bortezomib alone.”

The researchers conducted a proof-of-concept, open-label, Phase 2 study in which 150 patients with RRMM were randomly assigned to received elotuzumab with bortezomib and dexamethasone (EBd) or bortezomib and dexamethasone (Bd) until disease progression or unacceptable toxicity was reached. Primary endpoint was progression-free survival (PFS); secondary and exploratory endpoints included overall response rate (ORR) and overall survival (OS).

Patients treated with elotuzumab achieved longer median PFS (9.7 months vs. 6.9 months). These data equated to a 28% reduction in the risk for progression or death compared with the standard of care alone —  and the study met its primary endpoint.

Of the patients treated with elotuzumab, 13 who were homozygous (carried the same two forms of a gene) for the high-affinity FcRIIIa V (VV) allele  (variant form of a gene) demonstrated a median PFS of 22.3 months, while 24 who were homozygous for the low-affinity FcRIIIa F (FF) allele demonstrated a median PFS of 9.8 months. Patients homozygous for the V allele assigned standard of care had a median PFS of 8.2 months.

The ORR for patients assigned elotuzumab was 66%, compared with 63% among patients assigned standard of care. Thirty-six percent of patients in the elotuzumab arm and 27% of patients in the standard of care arm achieved a very good partial response or better.

Patients assigned elotuzumab had a median duration response of 11.4 months compared with 9.3 months for standard of care.

The researchers reported one-year OS based on 40 deaths. Rates of one-year OS were 85% in the elotuzumab arm and 74% in the standard of care arm.

A two-year analysis based on 60 deaths showed a two-year OS rate of 73% for elotuzumab and 66% for standard of care.

Follow-up for mature OS data remains ongoing.

Researchers wrote in the study: “Further investigation of elotuzumab with a proteasome inhibitor, including carfilzomib or ixazomib, is warranted.”

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