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.
References
Original article
Dimopoulos, M. A. et al. Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N. Engl. J. Med. 379, 1811–1822 (2018)
Further reading
Chari, A. et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood 130, 974–981 (2018)
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Killock, D. Second elotuzumab triplet efficacious in MM. Nat Rev Clin Oncol 16, 67 (2019). https://doi.org/10.1038/s41571-018-0137-5
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DOI: https://doi.org/10.1038/s41571-018-0137-5