Relapsed/refractory patients

European Commission approves elotuzumab plus pomalidomide and low-dose dexamethasone for relapsed and refractory multiple myeloma

On 28th August 2019, the European Commission (EC) approved the combination of elotuzumab (E) - a SLAMF7-directed immunostimulatory antibody - with pomalidomide (P) and low-dose dexamethasone (d; EPd) for the treatment of adult patients with relapsed and refractory (R/R) multiple myeloma (MM) who have received at least two previous therapies, including lenalidomide and a proteasome inhibitor (PI), and have demonstrated disease progression on the last treatment.1

The approval of the EPd triplet regimen was based on the results of the phase II ELOQUENT-3 trial (previously reported by the MM Hub). In this trial, 117 heavily pretreated patients with R/R MM were randomized to either EPd (n=60) or standard-of-care Pd (n=57), in 28-day cycles, until disease progression or intolerable toxicity.  Results demonstrated that EPd had doubled both median progression-free survival (PFS; primary endpoint) and overall response rate (ORR; secondary endpoint) compared with Pd:1

  • Median investigator-assessed PFS: 10.25 months (95% CI: 5.59–not estimable [NE]) with EPd vs 67 months (95% CI: 2.83–7.16) with Pd
    • 46% risk reduction of disease progression (HR 0.54; 95% CI: 0.34–0.86; p=0.0078) after a minimum follow-up of 9.1 months
  • ORR: 53.3% (95% CI: 40.0–66.3) with EPd compared with 26.3% (95% CI: 15.5–39.7; p=0.0029) with Pd

Serious adverse events (SAEs) were experienced by 22% of patients in the EPd arm vs 15% with Pd. The most frequent SAEs in the EPd arm compared with the Pd arm were pneumonia (13% vs 11%) and respiratory tract infection (7% vs 3.6%). The most common AEs occurring in ≥20% of patients treated with EPd and Pd, respectively, were constipation (22% vs 11%) and hyperglycemia (20% vs 15%).

Updated data from the ELOQUENT-3 trial, with a minimum of 18.3 months of follow-up, were presented earlier this year at the 24th Congress of the EHA.2 In the extended follow-up, EPd was associated with a 46% reduction in the risk of death vs Pd (HR 0.54, 95% CI 0.30–0.96). Median OS was not reached (24.9–NE) with EPd vs 17.4 months (13.8–NE) with Pd. OS rates (EPd vs Pd) were 68% with EPd vs 49% with Pd. Safety results were consistent with the primary analysis, with no new safety signals.

Approval history

In November 2018, the U.S. Food and Drug Administration (FDA) approved EPd for the treatment of adult patients with MM. The MM hub also reported the updated efficacy results with a minimum follow-up of 18.3 months that were presented at the 24th Congress of the EHA, 2019.3

Elotuzumab was initially approved by the U.S. Food and Drug Administration (FDA) in 2015 in combination with lenalidomide (R) and dexamethasone (ERd) for the treatment of patients with MM who have received 1–3 prior therapies (ELOQUENT-2; NCT01239797). In 2018, elotuzumab was approved by the FDA in a new combination, with pomalidomide and dexamethasone, for the treatment of patients with MM who have received at least two prior therapies, including lenalidomide and a PI (ELOQUENT-3). The EC subsequently approved ERd and EPd indications in 2016 and 2019, respectively. 

References
  1. Bristol-Myers Squibb. European Commission approves Empliciti® (elotuzumab) plus pomalidomide and low-dose dexamethasone (EPd) for the treatment of patients with relapsed and refractory multiple myeloma. https://news.bms.com/press-release/corporatefinancial-news/european-commission-approves-empliciti-elotuzumab-plus-pomalid [Accessed 28 August 2019]
  2. Dimopoulos M. et al., Elotuzumab plus pomalidomide and dexamethasone for relapsed/refractory multiple myeloma: efficacy results after additional follow-up of the phase 2, randomized ELOQUENT-3 study. Poster presented at: 24th congress of the European Hematology Association (EHA); June 15 2019; Amsterdam, NL. Poster #PS1370
  3.  BusinessWire. European Commission approves Empliciti® (elotuzumab) plus pomalidomide and low-dose dexamethasone (EPd) for the treatment of patients with relapsed and refractory multiple myeloma. https://www.businesswire.com/news/home/20190827005768/en/European-Commission-Approves-Empliciti-elotuzumab-Pomalidomide-Low-Dose [Accessed 28 August 2019]
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