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EPd Triplet Therapy Boosts Survival in R/R MM Vs. Pd

October 27, 2022

November 2022

Treatment with elotuzumab plus pomalidomide/­dexamethasone (EPd) resulted in a significant reduction in the risk of death compared with pomalidomide/dexamethasone (Pd) in patients with relapsed or refractory multiple myeloma (R/R MM) who had previously received lenalidomide and a proteasome inhibitor (PI). This suggests the triplet regimen may offer clinically valuable benefits when used as a third-line or later treatment, according to findings from the phase II ELOQUENT-3 trial published in the Journal of Clinical Oncology.

Researchers said these results complement the final overall survival (OS) results from ELOQUENT-2, which demonstrated a benefit of elotuzumab plus lenalidomide/dexamethasone in improving OS compared with lenalidomide/dexamethasone in patients with R/R MM who had received one to three prior lines of treatment.

However, the investigators explained, previous research has not yet shown a benefit with elotuzumab-based combinations in patients with newly diagnosed MM, suggesting these combinations have not shown benefit as early-line treatment.

Patients were randomly assigned to receive EPd (n=60) or Pd (n=57), stratifying assignments based on the number of prior lines of treatment. Treatment was administered in 28-day cycles until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent.

Treatment with EPd consisted of intravenous elotuzumab 10 mg/kg once daily on days one, eight, 15, and 22 during cycles one and two, as well as 20 mg/kg on day one of each cycle thereafter. Both treatment groups received oral pomalidomide 4 mg once daily on days one through 21 of each cycle. Additionally, oral dexamethasone 40 mg or 20 mg was administered once weekly in patients older than 75 years, except on days when elotuzumab was administered and patients in the elotuzumab group received dexamethasone both orally (28 mg in patients 75 years or younger or 8 mg in patients older than 75) and intravenously (8 mg).

Progression-free survival (PFS), per investigator assessment, was the study’s primary endpoint. Additionally, the researchers evaluated overall response rate (ORR) and OS as secondary endpoints.

The median ages of patients in the EPd and Pd groups were 68.5 and 66.0 years, respectively. Patients in each group received a median of three previous lines of therapy. Most patients – 68.3% in the EPd group and 71.9% in the Pd group – had disease that was refractory to both lenalidomide and a PI. Lenalidomide was received as the last line of therapy in more patients in the EPd group, but patients assigned to Pd had a higher rate of high-risk disease and worse renal function.

A total of 37 deaths in the EPd group (61.7%) and 41 deaths in the Pd group (74.5%) were reported in the treated population. Deaths were most commonly a result of disease progression, which was reported in 41.7% of patients in the EPd arm and 49.1% in the Pd group.

Based on a primary analysis, researchers reported a significant improvement in PFS with EPd versus Pd (hazard ratio [HR] = 0.54, 95% CI 0.34-0.86; p=0.008). After a minimum follow-up of 9.1 months, the median PFS was 10.3 months in the EPd group compared to 4.7 months in the Pd group.

The median OS also significantly improved with EPd versus Pd (29.8 vs. 17.4 months, respectively), with an HR of 0.59 (95% CI 0.37-0.93; p=0.0217) that corresponded with a 41% reduction in the risk of death with EPd relative to Pd. The OS rates were also higher with EPd at one year (79% vs. 68%), two years (63% vs. 44%), and three years (39% vs. 29%). The benefit of EPd versus Pd on OS was observed consistently across subgroups with respect to age, refractory disease, and previous number of treatment lines.

Regarding safety, the investigators stated that “the safety profile of EPd was consistent with prior reports,” and the researchers detected no new safety signals associated with the triplet regimen.

The primary limitation of the study included its small sample size, which the researchers suggested limits the interpretability of the subgroup analyses on OS.

Any conflicts of interest declared by the authors can be found in the original article.

Reference

Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus pomalidomide and dexamethasone for relapsed/refractory multiple myeloma: final overall survival analysis from the randomized phase II ELOQUENT-3 trial [published online ahead of print, 2022 Aug 12]. J Clin Oncol. doi: 10.1200/JCO.21.02815.

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