Elotuzumab in Relapsed/Refractory Multiple Myeloma

Elotuzumab is a monoclonal antibody being evaluated for patients with relapsed or refractory multiple myeloma, says Madhav Dhodapkar, MD. It targets the SLAMF7 protein, which is expressed on myeloma cells but also expressed on natural killer (NK) cells. This allows elotuzumab to directly engage the myeloma cell via antibody-dependent cell-mediated cytotoxicity as well as activate NK cells to promote killing of myeloma cells.

The phase III clinical trial, ELOQUENT-2, randomized individuals with multiple myeloma to receive elotuzumab with lenalidomide and dexamethasone or lenalidomide and dexamethasone. Patients who received the triplet demonstrated improved progression free survival, notes Dhodapkar. At a median follow-up of 2 years, PFS with the elotuzumab regimen was 19.4 months versus 14.9 months with lenalidomide and dexamethasone alone (HR, 0.70; P = .0004). The 2-year PFS rates were 41% and 27%, in the elotuzumab and control arms, respectively.

The primary adverse events (AE) with elotuzumab are infusion reactions, which are common all monoclonal antibodies, comments Dhodapkar. In the ELOQUENT-2 trial, grade 3/4 AEs occurring in ≥15% of patients in the elotuzumab versus control arm were neutropenia (25% vs 33%) and anemia (15% vs 16%).

A phase II clinical study assessed the use of bortezomib and dexamethasone with and without elotuzumab in relapsed/refractory multiple myeloma and showed a comparable reduction in the risk of progression with the addition of elotuzumab as was seen in the ELOQUENT-2 trial (HR, 0.72). The overall activity of elotuzumab, bortezomib, and dexamethasone appears to be comparable to elotuzumab, lenalidomide, and dexamethasone, suggests, Dhodapkar.

Bortezomib is a significantly immunosuppressive drug, adds Ivan Marques Borrello, MD. One of the interesting findings with elotuzumab is that it was not very effective as a single agent, but it has shown good efficacy in combination with other agents. Moving forward, clinical trials will need to address whether patients should stop taking these immunotherapy-based agents or if treatment should be continued, notes Borrello.