Triplet Regimen Failed to Improve Outcomes in Newly Diagnosed MM

The addition of elotuzumab to lenalidomide and dexamethasone did not improve progression-free survival (PFS) compared with lenalidomide and dexamethasone alone in patients with newly diagnosed multiple myeloma (MM) who are ineligible for hematopoietic stem cell transplantation (HSCT), according to results of the ELOQUENT-1 trial.

This information comes despite the fact that the three-drug combination improved both PFS and overall survival in the relapsed/refractory setting. The researchers said the reasons for the failure to improve outcomes in the newly diagnosed setting are “unknown and likely multifactorial”.

The open-label, phase III trial included 748 patients from 19 countries. Patients had newly diagnosed disease and were not candidates for high-dose therapy plus HSCT. Patients were randomized to receive elotuzumab plus lenalidomide and dexamethasone or lenalidomide and dexamethasone alone. The median patient age was 73 years, and 39% of patients were aged 75 years or older.

With a minimum follow-up of 65.3 months, the median PFS was not significantly different between the two treatment groups (31.4 months with elotuzumab vs 29.5 months without; hazard ratio=0.93; 95% CI, 0.77-1.12).

The researchers noted that the time to an accumulation of events required for PFS analysis was 65 months compared with the estimated time of 29 months.

The overall response rate was 83% with elotuzumab compared with 79% without elotuzumab. Median time to best response and mediation duration of response were similar for both treatment groups.

Treatment with elotuzumab plus lenalidomide and dexamethasone was well-tolerated and showed no new safety signals.

“The negative results from first-line trials of elotuzumab plus lenalidomide and dexamethasone, carfilzomib-based studies (including carfilzomib plus lenalidomide and dexamethasone), and ixazomib plus lenalidomide and dexamethasone studies might reflect the broader difficulty of showing treatment superiority in the newly diagnosed setting, possibly because of differences in disease biology, higher clinical burden of disease, and larger differences in outcomes needed to show a treatment effect,” the researchers wrote.

Dimopoulos MA, Richardson PG, Bahlis NJ, et al. Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomized, phase 3 trial. Lancet Haematol. 2022. doi:10.1016/ S2352-3026(22)00103-X