Novel Agent Elotuzumab Added to Lenalidomide/Dexamethasone Extends Progression-Free Survival in Multiple Myeloma


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Sagar Lonial, MD

Elotuzumab in Multiple Myeloma

We are very excited about the fact that there was such a big difference in progression-free survival between the arms, and we attribute this to a novel first-in-class antibody.

—Sagar Lonial, MD

The monoclonal antibody elotuzumab, given with lenalidomide (Revlimid) and dexamethasone, extended progression-free survival by a median of 5 months, compared with lenalidomide/dexamethasone alone, in the eagerly awaited phase III ELOQUENT-2 trial, which will be presented at the 2015 ASCO Annual Meeting (abstract 8508, being presented June 2, 2015).1 The results were reported at a press briefing in advance of the meeting by Sagar Lonial, MD, Professor and Executive Vice Chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine, Atlanta.

“Elotuzumab, a monoclonal antibody with a novel immunotherapeutic mechanism of action, showed improved progression-free survival, with minimal added toxicity, in combination with lenalidomide/dexamethasone vs lenalidomide/dexamethasone alone,” Dr. Lonial reported. “We are very excited about the fact that there was such a big difference in progression-free survival between the arms, and we attribute this to a novel first-in-class antibody.” He added, “it was particularly striking that the difference between the elotuzumab and control groups seems to get bigger over time, which speaks to the power of this immune-based approach.”

“A unique attribute of elotuzumab is that it appears to have a dual mechanism of action, targeting the tumor cell and enhancing the activation of natural killer cells,” Dr. Lonial said. “Natural killer cells make the targeting of myeloma cells with elotuzumab more effective; it’s a double whammy on the tumor.”

Elotuzumab received breakthrough status from the U.S. Food and Drug Administration last year, in combination with lenalidomide and dexamethasone, for treating relapsed multiple myeloma.

ELOQUENT-2 Details

ELOQUENT-2 is the largest study of a monoclonal antibody in multiple myeloma and the first phase III trial showing a benefit using a targeted immune-based approach in treating this disease.

The study included 646 relapsed patients, who had received a median of two prior therapies, including bortezomib (Velcade, 70%), thalidomide (Thalomid, 48%), and lenalidomide (6%).  Subjects were randomly assigned to receive lenalidomide/dexamethasone (control group) or the same regimen plus elotuzumab. Elotuzumab was given at 10 mg/kg in weekly cycles 1 and 2 and then biweekly. Lenalidomide was given at 25 mg on days 1 to 21; dexamethasone was given weekly (40 mg on weeks when elotuzumab was given, 28 mg orally plus 8 mg intravenously). 

After a median follow-up of 24 months, elotuzumab significantly reduced the risk of disease progression and death by 30%. Median progression-free survival was 19.4 months with elotuzumab plus lenalidomide/dexamethasone, compared with 14.9 months with lenalidomide/dexamethasone (P = .0004). Progression-free survival was 68% in the elotuzumab arm vs 57% in the control arm at 1 year and 41% and 27%, respectively, at 2 years.

“What was striking about this progression-free survival curve, compared with many others you will see, is that the two curves don’t appear to come back together at longer follow-up. The idea of maintenance of benefit over time speaks to the power of an immune-based approach in cancer,” Dr. Lonial said.

The progression-free survival benefit with the three drugs was consistent across key subgroups, including patients with high-risk cytogenetic profiles, he added. The triplet also increased the objective response rate, a second primary endpoint, from 66% to 79% (P = .0002).

Toxicity

The three-drug combination was well tolerated. Grade 3-4 adverse events occurring in at least 15% of patients, for the elotuzumab arm vs the control arm, included neutropenia (25% vs 33%) and anemia (15% vs 16%). 

“The improvement in clinical parameters occurred without a significant increase in adverse events or toxicity,” he commented. “In fact, there was no reduction in quality of life for the group getting three drugs.”

As of the data cutoff (November 2014), 35% of the elotuzumab group and 21% of the control group remained on therapy. There were 210 deaths, including 94 in the elotuzumab arm and 116 in the control arm. ■

Disclosure: The study was funded by Bristol-Myers Squibb and AbbVie. Dr. Lonial reported having a consulting or advisory role with Bristol-Myers Squibb, Onyx, Celgene, Millennium, Janssen, and Novartis Healthcare A/S.

Reference

1. Lonial S, et al: 2015 ASCO Annual Meeting. Abstract 8508. To be presented June 2, 2015.

 


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