Top Takeaways from ASH: ELOQUENT-2 trial results of elotuzumab demonstrate immune effects

Elotuzumab, the third drug to be approved by the FDA for multiple myeloma in a 2-week span in November 2015, is the first immunostimulatory monoclonal antibody to demonstrate a notable improvement in efficacy without an increase in toxicity.

Updated results of the ELOQUENT-2 trial – a phase 3, randomized, open-label study – presented at the ASH Annual Meeting and Exposition focused on 3-year follow-up data. Results of the ELOQUENT-2 trial were one of several studies presented that focused on triple therapy combinations for multiple myeloma.

“Elotuzumab (Empliciti, Bristol-Myers Squibb) is a novel monoclonal antibody against this antigen known as [Signaling Lymphocytic Activation Molecule F7 (SLAMF7)],” said John Sweetenham, MD, chief medical editor of hematology for HemOnc Today and senior director of clinical affairs and executive medical director at Huntsman Cancer Institute at University of Utah. “This agent was added to other standard agents in a triple therapy combination and it produced very high response rates.”

ELOQUENT-2

The 3-year safety and efficacy follow-up data from Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens School of Medicine in Athens, Greece, and colleagues presented at ASH included 646 patients with relapsed and/or refractory multiple who had been treated with a median of 2 prior therapies. The median age of patients was 66 years, with 20% over the age of 75 years, and 35% of study participants were refractory to their last line of therapy.

Patients were randomly assigned to elotuzumab in combination with lenalidomide (Revlimid, Celgene) and dexamethasone (n = 321) or lenalidomide and dexamethasone (n = 325). At the data cutoff point, 29% of patients in the elotuzumab, lenalidomide and dexamethasone group remained on treatment vs. 15% of patients in the lenalidomide-dexamethasone group. Continued improvement in worst pain, as measured by the Brief Pain Inventory - Short Form scale, was noted in patients who achieved an overall response rate. Discontinuation was due primarily to disease progression in both the elotuzumab, lenalidomide and dexamethasone (46%) and the lenalidomide-dexamethasone (51%) arms.

Grade 3 to 4 adverse events were reported in ≥ 15% of patients and included lymphopenia, neutropenia, anemia and thrombocytopenia. Infections of any grade occurred in 83% of patients in the elotuzumab, lenalidomide and dexamethasone arm and 75% in the lenalidomide-dexamethasone arm. Infusion reactions, most of which were Grade 1–2, occurred in 11% of patients treated with elotuzumab, lenalidomide and dexamethasone.

There were 263 deaths during treatment follow-up. One hundred twenty-three (47%) were reported in the elotuzumab, lenalidomide and dexamethasone arm and 140 (53%) were reported in the lenalidomide and dexamethasone arm.

Results emphasize role of triple therapy, immune effects

Like daratumumab (Darzalex, Janssen), another recently approved agent for multiple myeloma, elotuzumab is a monoclonal antibody, but “it works in a slightly different way,” according to Mitchell R. Smith, MD, PhD, director of the Lymphoid Malignancy Program at Cleveland Clinic Taussig Cancer Institute.

“[Elotuzumab] doesn’t have much single-agent activity,” Smith told Healio.com. “It seems to act as an immune-modulating enzyme, so it needs to be given with other standard treatments.”

Sweetenham called the activity against SLAMF7 “quite interesting.”

“[Elotuzumab] … probably has immune effects as well as directly acting upon myeloma cells,” he said.

The efficacy of elotuzumab is clear, according to Smith, but the way in which the drug will be delivered in combination with other agents is not yet as well-defined.

In addition to elotuzumab and daratumumab, ixazomib (Ninlaro, Takeda Pharmaceuticals) was also approved for multiple myeloma in November 2015. The approval of these agents, and the results presented at ASH, highlight the theme that “three drugs are better than two,” according to Sweetenham.

Ajai Chari, MD, associate professor of medicine – hematology and medical oncology, at the Icahn School of Medicine at Mount Sinai, commented on the results of ELOQUENT-2 in the broader context of the recently approved agents for multiple myeloma.

“For the two groups of patients that continue to have inferior outcomes in the current era – genomically high-risk patients and the elderly – the monoclonal antibodies are particularly exciting for different reasons – a novel immunologic mechanism of action and tolerability, respectively,” Chari said. “We also heard … that elotuzumab could be combined with bortezomib [Velcade] and improved efficacy. So, if you had to pick one thing that really was the biggest splash, it was the combination of monoclonal antibodies with our currently approved drug classes to demonstrate not only safety, but improved efficacy.” – by Julia Ernst, MS 

Reference:

Dimopoulos MA, et al. Abstract 28. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Disclosure: Dimopoulos reports receiving honoraria from Amgen, Celgene, Genesis, Janssen, Janssen-Cilag, Novartis and Onyx. Please see the abstract for a list of all other researchers’ relevant financial disclosures.