Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial

Abstract

Purpose: In the phase II ELOQUENT-3 trial (ClinicalTrials.gov identifier: NCT02654132), elotuzumab combined with pomalidomide/dexamethasone (EPd) significantly improved progression-free survival (PFS) versus pomalidomide/dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma (RRMM) previously treated with lenalidomide and a proteasome inhibitor (PI). Here, we present the final overall survival (OS) results.

Methods: Patients with RRMM who had received ≥ 2 prior lines of therapy, with disease refractory to last therapy and either refractory or relapsed and refractory to lenalidomide and a PI were randomly assigned (1:1) to receive EPd or Pd. The primary end point was PFS per investigator assessment. ORR and OS were secondary end points planned to be tested hierarchically.

Results: A total of 117 patients were randomly assigned to EPd (n = 60) and Pd (n = 57). Among treated patients (EPd 60, Pd 55), there were 37 (61.7%) deaths in the EPd group and 41 (74.5%) in the Pd group, most commonly because of disease progression (EPd 41.7%, Pd 49.1%). Median (95% CI) OS was significantly improved with EPd (29.8 [22.9 to 45.7] months) versus Pd (17.4 [13.8 to 27.7] months), with a hazard ratio of 0.59 (95% CI, 0.37 to 0.93; P = .0217). OS benefit with EPd was observed in most patient subgroups. The safety profile of EPd was consistent with prior reports with no new safety signals detected.

Conclusion: EPd demonstrated a statistically significant improvement in OS versus Pd in patients with RRMM previously treated with lenalidomide and a PI who had disease refractory to last therapy. In this setting, ELOQUENT-3 is the first randomized study of a triplet regimen incorporating a monoclonal antibody and Pd to improve both PFS and OS significantly.

Conflict of interest statement

Mihaela Popa McKiver

Employment: Briston Myers Squibb

Stock and Other Ownership Interests: Briston Myers Squibb

Ying-Ming Jou

Employment: Bristol Myers Squibb/Celgene

Stock and Other Ownership Interests: Bristol Myers Squibb/Celgene

Paul G. Richardson

Consulting or Advisory Role: Takeda, Karyopharm Therapeutics, Oncopeptides, Sanofi, Jazz Pharmaceuticals, Secura Bio, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Regeneron, AstraZeneca

Research Funding: Celgene (Inst), Takeda (Inst), Bristol Myers Squibb (Inst), Oncopeptides (Inst), Karyopharm Therapeutics (Inst)

Dominik Dytfeld

Honoraria: Janssen, Celgene/Bristol Myers Squibb, Amgen, Takeda

Consulting or Advisory Role: Amgen, Janssen, Celgene/Bristol Myers Squibb, Takeda

Research Funding: Janssen, Celgene

Xavier Leleu

Honoraria: Janssen-Cilag, Celgene, Amgen, Novartis, Bristol Myers Squibb, Takeda, Sanofi, AbbVie, Merck, Roche, Karyopharm Therapeutics, CARsgen Therapeutics, Oncopeptides, GlaxoSmithKline

Consulting or Advisory Role: Janssen-Cilag, Celgene, Amgen, Takeda, Bristol Myers Squibb, Novartis, Merck, Gilead Sciences, AbbVie, Roche, Karyopharm Therapeutics, Oncopeptides, CARsgen Therapeutics, GlaxoSmithKline

Travel, Accommodations, Expenses: Takeda

David Yao

Employment: Bristol Myers Squibb, Janssen

Stock and Other Ownership Interests: Bristol Myers Squibb

Travel, Accommodations, Expenses: Bristol Myers Squibb, Janssen

Meletios A. Dimopoulos

Honoraria: Amgen, Takeda, Janssen-Cilag, Bristol Myers Squibb, Beigene

Consulting or Advisory Role: Amgen, Janssen-Cilag, Takeda, Bristol Myers Squibb, Beigene

Richard LeBlanc

Consulting or Advisory Role: Janssen, BMS Canada, Amgen, Sanofi, FORUS Therapeutics

Prianka Das

Employment: Bristol Myers Squibb/Celgene

Stock and Other Ownership Interests: Bristol Myers Squibb/Celgene (Inst)

Philippe Moreau

Honoraria: Celgene, Janssen-Cilag, Amgen, GlaxoSmithKline, AbbVie, Sanofi, Oncopeptides

Consulting or Advisory Role: Celgene, Janssen, Amgen, GlaxoSmithKline, Sanofi, AbbVie, Oncopeptides

Marc S. Raab

Honoraria: AbbVie, Bristol Myers Squibb/Celgene, Takeda, GlaxoSmithKline

Consulting or Advisory Role: Bristol Myers Squibb/Celgene (Inst), Amgen (Inst), GlaxoSmithKline (Inst), Janssen (Inst), Sanofi (Inst), Pfizer (Inst)

Research Funding: Bristol Myers Squibb/Celgene (Inst), Janssen (Inst), Sanofi (Inst), Novartis (Inst)

Travel, Accommodations, Expenses: AbbVie, Bristol Myers Squibb/Celgene, Takeda, GlaxoSmithKline, Amgen, Janssen, Sanofi, Pfizer

Jesús San-Miguel

Consulting or Advisory Role: Amgen (Inst), Celgene (Inst), Takeda (Inst), Bristol Myers Squibb (Inst), MSD (Inst), Novartis (Inst), Sanofi (Inst), Janssen (Inst), Roche (Inst), AbbVie (Inst), GlaxoSmithKline (Inst), Karyopharm Therapeutics (Inst), Secura Bio (Inst), Regeneron (Inst), Haemalogix (Inst)

No other potential conflicts of interest were reported

Figures

FIG 1.

Patient disposition (CONSORT diagram). AE, adverse event; EPd, elotuzumab plus pomalidomide/dexamethasone; Pd, pomalidomide/dexamethasone.

FIG 2.

OS (all randomly assigned patients). EPd, elotuzumab plus pomalidomide/dexamethasone; HR, hazard ratio; OS, overall survival; Pd, pomalidomide/dexamethasone.

FIG 3.

(A) OS in key patient subgroups. (B) Overall survival of patients receiving lenalidomide as their most recent prior line of therapy. NOTE: In (A), HR for the overall population was based on analysis stratified by ISS stage at study entry (I-II v III) and number of prior lines of therapy (2-3 v ≥ 4) at random assignment. HRs for the individual subgroups were based on unstratified analysis. EPd, elotuzumab plus pomalidomide/dexamethasone; HR, hazard ratio; ISS, International Staging System; LDH, lactate dehydrogenase; OS, overall survival; Pd, pomalidomide/dexamethasone; PI, proteasome inhibitor.