In 2015, the FDA approved the anti-SLAMF7 antibody elotuzumab, lenalidomide and dexamethasone triplet regimen for the treatment of relapsed and/or refractory multiple myeloma (RRMM) after ≥1 prior line of therapy. Now, data from the randomized, open-label, phase II ELOQUENT-3 trial demonstrate the efficacy of a different elotuzumab-containing triplet in the lenalidomide-refractory setting.

ELOQUENT-3 involved 117 patients with RRMM after ≥2 previous treatments, including a proteasome inhibitor as well as lenalidomide, in a population with a poor prognosis. Indeed, in this trial, control treatment with the FDA-approved pomalidomide and dexamethasone (Pd) regimen resulted in an investigator-assessed overall response rate (ORR) of 26% and median progression-free survival (PFS) of 4.7 months. However, adding elotuzumab to form the EPd triplet increased the ORR to 53% and the median PFS to 10.3 months (HR 0.54, 95% CI 0.34–0.86; P = 0.008), and was corroborated upon blinded, independent review. Notably, the PFS benefit of EPd was consistent across key high-risk patient subgroups. At 40% maturity, overall survival data revealed an intriguing trend favouring EPd (HR 0.62, 95% CI 0.30–1.28).

Infection and grade 3–4 adverse events were similarly common with EPd and Pd. Interestingly, however, EPd was associated with lower rates of neutropenia (13% versus 27%), anaemia (10% versus 20%) and treatment discontinuation (18% versus 24%). Only 3 patients had EPd-infusion reactions.

On 6 November 2018, the FDA approved EPd for this indication. Another triplet regimen consisting of the anti-CD38 antibody daratumumab plus Pd is approved in the same setting and has been associated with an ORR of 60% and a median PFS of 8.8 months, suggesting similar efficacy to EPd, but also with high rates of neutropenia (80%) and infusion reactions (50%). Additional trials are needed to compare the safety and efficacy of these triplets.