European Commission Approves Empliciti Triple Combo for Advanced Multiple Myeloma

The European Commission (EC) has approved Empliciti (elotuzumab) in combination with Pomalyst (pomalidomide) and low-dose dexamethasone for the treatment of adults with relapsed and refractory multiple myeloma.

The therapy, collectively known as the EPd combo, is intended for patients who received at least two prior therapies, including Revlimid (lenalidomide) and a proteasome inhibitor (PI), and whose disease progressed while they were completing their last course of treatment.

In 2016, the EC approved Empliciti in combination with Revlimid and dexamethasone for the treatment of patients with multiple myeloma who had received at least one prior therapy. The EPd combo is the second Empliciti-based combination therapy approved for the treatment of multiple myeloma in the European Union.

“Multiple myeloma is a frequently recurring disease and the chance it will return after initial treatment is a heavy burden for patients to carry,” Fouad Namouni, MD, head of oncology development at Bristol-Myers Squibb, said in a press release. “We are proud that the European Commission has again recognized the role of Empliciti in helping European patients with multiple myeloma by approving a second Empliciti-based regimen in the relapsed and refractory setting.”

Empliciti is an antibody therapy co-developed by Bristol-Myers Squibb and AbbVie that binds to a protein called SLAMF7. This protein is found on the surface of myeloma cells and anti-tumor natural killer (NK) cells, a type of immune cells that recognize and destroy other cells or microbes seen as threats by the immune system.

The medication has two different mechanisms of action. It stimulates the immune system to fight myeloma by activating NK cells through SLAMF7, and helps tag cancer cells to be destroyed by NK cells by binding to them.

A few months ago, the Committee for Medicinal Products for Human Use (CHMP), a branch of the European Medicines Agency (EMA), recommended the approval of the triple combination for the treatment of patients with advanced multiple myeloma who had already been treated with at least two different therapies.

Following CHMP’s positive recommendation, the EC has decided to approve the EPd combo for the treatment of these patients in the E.U. The U.S. Food and Drug Administration (FDA) had already approved the EPd combo for the same indication in November 2018.

The approval was based on findings from the global, open-label, randomized, ELOQUENT-3 Phase 2 trial (NCT02654132).

The study assessed the effects of adding Empliciti to standard treatment with Pomalyst and low-dose dexamethasone (Pd combo) in 117 patients with relapsed or refractory multiple myeloma whose disease worsened despite treatment with at least two prior therapies.

Study participants were randomly assigned to either the EPd combo or the standard Pd combo in treatment cycles of 28 days, until disease progression or unacceptable toxicity. Key findings from the trial, presented by Bristol-Myers at the 23^rd European Hematology Association Congress in Stockholm last year, have shown that:

• The EPd combo significantly increased the time patients lived without their disease worsening compared to the Pd combo (10.3 months versus 4.7 months), lowering the risk of disease progression and death by 46%;
• The EPd combo doubled the response rate of patients compared to the Pd combo (53% versus 26%);
• The incidence of severe (grade 3) and life-threatening (grade 4) adverse events was similar in patients from both groups;
• Infections (any degree of severity) occurred in 65% of the patients from both groups;
• Severe or life-threatening neutropenia (27% versus 13%) and anemia (20% versus 10%) were more common among patients treated with the Pd combo than among those receiving the EPd combo;
• A higher proportion of patients in the Pd group had to discontinue treatment because of adverse events than in the EPd group (24% versus 18%).

This year, the company presented updated efficacy data from ELOQUENT-3 at the 24^th European Hematology Association Congress in Amsterdam.

Trial findings showed that after 18.3 months of follow-up, 67% of the patients in the EPd group were alive, whereas only 51% of those in the Pd group were alive. The median overall survival was 17.4 months in patients treated with the Pd combo and was not reached for those receiving the EPd combo, indicating the treatment response in the EPd group was more sustained.

“The approval of this elotuzumab-based triplet combination in the relapsed and refractory setting gives patients, and their doctors, a treatment alternative shown to have the potential to offer patients more time living without disease progression, coupled with a tolerable safety profile,” said Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens.