Zosia Chustecka

May 15, 2015

An innovative investigational agent that targets natural killer (NK) cells has shown benefit in the treatment of multiple myeloma, the first time that an immune approach has been shown to work in this disease.

The novel product, elotuzumab (Bristol-Myers Squibb/AbbVie), is a monoclonal antibody that targets the cell-surface protein SLAMF7, which is found both on myeloma cells and on NK cells. It offers a two-pronged attack on cancer by targeting myeloma cells directly and by enhancing the NK cells' ability to kill myeloma cells.

"It's a bit of a double whammy," commented lead study author Sagar Lonial, MD, chief medical officer of the Winship Cancer Institute of Emory University and professor and executive vice chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta.

Dr Lonial was speaking at a presscast ahead of the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting, where a phase 3 study with the new drug will be presented. The study is known as ELOQUENT-2 (NCT01239797).

In that phase 3 trial, conducted in 646 patients with relapsed multiple myeloma, adding elotuzumab to standard therapy with lenalidomide (Revlimid, Celgene) and dexamethasone extended the duration of remission by a median of 5 months, compared with standard therapy alone (median progression-free survival was 19.4 months vs 14.9 months).

"It was particularly striking that the difference between the elotuzumab and control groups seems to get bigger over time, which really speaks to the power of this immune-based approach," Dr Lonial commented. This separation of the curves and the maintenance of benefit over time has been seen with other immune-based approaches, such as program death inhibitors, he added.

Elotuzumab has been granted breakthrough product designation for this use (in combination with lenalidomide and dexamethasone in relapsed multiple myeloma) by the US Food and Drug Administration.

The patients who were eligible for this trial had relapsed or refractory myeloma, but they were still in the early phase of their disease, Dr Lonial explained, having had been treated with one to three prior therapies (median was two; range was one to four). The prior therapies included bortezomib (Velcade, Janssen) in 70% of cases, thalidomide (Thalomid, Celgene) in 48%, and lenalidomide in 6%.

Dr Lonial said that adding elotuzumab to the standard therapy did not significantly increase the adverse events that were reported. Overall, the drug was well tolerated and did not deteriorate patient's quality of life or exacerbate symptom burden, and there was no detrimental effect on quality of life.

Mild infusion reactions (mostly grade 1/2) occurred after the first few doses in 10% of patients in the elotuzumab group, the researchers note.

Grade 3/4 adverse events that were reported in at least 15% patients included neutropenia (25% in the elotuzumab group vs 33% with standard therapy) and anemia (15% vs 16%). The exposure-adjusted infection rate was the same in both groups, the researchers note. Infusion reactions occurred in 10% of patients in the elotuzumab group.

The researchers also note that among the trial participants, two subgroups of patients with high-risk features ─ with the genetic abnormalities del(17p) and t(4;14) — appeared to benefit from elotuzumab as much as patients with average risk. Conventional therapies tend to be less effective in those high-risk patients, they add.

ASCO President-Elect Julie M. Vose, MD, MBA, commented: "We've made much headway over the past decade in understanding and treating multiple myeloma, the third most common blood cancer. This study is an innovative approach — one that combines the precision of a targeted, immune-based therapy with traditional myeloma therapy. The results are very encouraging, giving renewed hope to patients who have relapsed."

The study was funded by Bristol-Myers Squibb and AbbVie. Dr Lonial reports consulting or advisory roles with Onyx, Celgene, Bristol-Myers Squibb, Millennium, Janssen, and Novartis Healthcare. Several of his coauthors report relationships with various pharmaceutical companies, and four are employees of AbbVie or Bristol-Myers Squibb. Dr Vose reports receiving honoraria from sanofi-aventis; serving in consulting or advisory roles with Kite Pharma, Foundation Medicine, Seattle Genetics, Bank of America, KEW Group, and Bioconnections; receiving research funding from Bristol-Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Incyte Corporation, Janssen Biotech, Inc., Pharmacyclics, and US Biotest; and receiving expenses from Kite Pharma and Foundation Medicine.

American Society of Clinical Oncology (ASCO) 2015 Annual Meeting: Abstract 8508. To be presented on June 2, 2015.


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