Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed, transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomised, phase 3 trial.

BACKGROUND

Elotuzumab plus lenalidomide and dexamethasone has shown improved progression-free and overall survival versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. We aimed to assess these regimens in patients with newly diagnosed multiple myeloma who are ineligible for haematopoietic stem-cell transplantation (HSCT).

METHODS

ELOQUENT-1 is an open-label, multicentre, randomised, phase 3 trial conducted at 185 hospitals, oncology practices, and research centres in 19 countries. Eligible patients were aged 18 years or older with newly diagnosed, untreated, symptomatic myeloma and not candidates for high-dose therapy plus HSCT, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower. Patients were randomly assigned (1:1) to receive elotuzumab plus lenalidomide and dexamethasone or lenalidomide and dexamethasone using an interactive voice response system, stratified by the International Staging System (ISS; stage I-II vs III), age (<75 years vs ≥75 years), and ECOG performance status (0 vs 1-2). Patients in the elotuzumab plus lenalidomide and dexamethasone group received elotuzumab administered intravenously at 10 mg/kg on days 1, 8, 15, and 22 during cycles 1 and 2, days 1 and 15 during cycles 3-18, and then at 20 mg/kg on day 1 for subsequent cycles. In both treatment groups, patients received 25 mg lenalidomide orally on days 1-21 of each cycle and 40 mg dexamethasone on days 1, 8, 15, and 22 of each cycle. The primary endpoint was progression-free survival, as per the primary definition from European Society for Blood and Marrow Transplantation criteria in all randomly assigned patients (intention-to-treat population). This study is registered with ClinicalTrials.gov, NCT01335399 (completed).

FINDINGS

Between Aug 4, 2011, and June 19, 2014, 748 patients were randomly assigned (374 in each treatment group) and 742 patients received treatment (333 (90%) of 371 in the elotuzumab plus lenalidomide and dexamethasone group vs 339 (91%) of 371 in the lenalidomide and dexamethasone group discontinued treatment). The median age of patients was 73·0 years (IQR 69·0-78·0), 294 (39%) patients were 75 years or older. Most patients were White (711 [95%]) and male (412 [55%]). At a minimum follow-up of 65·3 months, the median progression-free survival was not significantly different between the groups: 31·4 months (95% CI 26·2-36·8) in the elotuzumab plus lenalidomide and dexamethasone group versus 29·5 months (23·5-34·3) in the lenalidomide and dexamethasone group (HR 0·93, 95·71% CI 0·77-1·12; stratified log-rank p=0·44). The median follow-up was 70·6 months (IQR 35·1-79·2). The most common grade 3-4 treatment-related adverse event was neutropenia (64 [17%] of 371 vs 79 [21%] of 371). Study drug toxicity was the reported cause of death in five (1%) versus four (1%) patients.

INTERPRETATION

Elotuzumab plus lenalidomide and dexamethasone did not significantly improve progression-free survival versus lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for HSCT. Although these data contribute to the treatment landscape, further research is needed to find ways to improve treatments in the front-line setting.

FUNDING

Bristol Myers Squibb.

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests MAD received personal fees from and served on advisory boards for Amgen, Bristol Myers Squibb, BeiGene, Janssen, and Takeda. PGR received personal fees from AstraZeneca, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Oncopeptides, Protocol Intelligence, Regeneron, Sanofi, Secura Bio, and Takeda; and grant funding from Bristol Myers Squibb, Celgene, Karyopharm, Oncopeptides, and Takeda. NJB received personal fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Janssen, Karyopharm, Pfizer, and Sanofi; and grant funding from Celgene. MC received personal fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Sanofi, and Takeda; and speakers bureau from Celgene and Janssen. MB served on speakers bureau for Amgen, Celgene, Janssen, Oncopeptides, Sanofi, and Takeda; and on advisory boards for Amgen, Celgene, Janssen, Sanofi, and Takeda. AML received grant funding, personal fees, and non-financial support from Bristol Myers Squibb; grant funding from AbbVie, Archigen, BeiGene, Celgene, FibroGen, GlaxoSmithKline, Janssen, Karyopharm, Novartis, MorphoSys, Onconova, Oncopeptides, Pfizer, Roche, Sanofi, Servier, Takeda, and Verastem; personal fees from AbbVie, Celgene, Incyte, Janssen, Novartis, and Servier; and non-financial support from AbbVie, Janssen, Novartis, Roche, Sanofi, Takeda, and Verastem. HG received grant funding or provision of investigational medicinal products, or both, from Amgen, Bristol Myers Squibb, Celgene, Chugai, the Dietmar Hopp Foundation, Janssen, Johns Hopkins University, and Sanofi; research support from Amgen, Bristol Myers Squibb, Celgene, Chugai, Janssen, Incyte, Molecular Partners, Merck Sharp and Dohme, Mundipharma, Novartis, Sanofi, and Takeda; has served on advisory boards for Adaptive Biotechnology, Amgen, Bristol Myers Squibb, Celgene, Janssen, Sanofi, and Takeda; and received honoraria from Amgen, Bristol Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Novartis, and Sanofi. AL received personal fees from Amgen, Bristol Myers Squibb, Celgene, Janssen, and GlaxoSmithKline, and Takeda. MTP received personal fees from Amgen, Bristol Myers Squibb, Janssen-Cilag, Celgene, GlaxoSmithKline, Karyopharm, Roche, Sanofi, and Takeda; and travel support from Amgen, Bristol Myers Squibb, Janssen-Cilag, Celgene, Sanofi, and Takeda. DW received personal fees from Amgen, Antengene, Bristol Myers Squibb, Janssen, Karyopharm, Sanofi, and Takeda. M-VM received personal fees from AbbVie, Adaptive, Amgen, Bluebird Bio, Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Seagen, and Takeda. IS received personal fees from GlaxoSmithKline; and personal fees and non-financial support from Amgen, Bristol Myers Squibb, Celgene, Janssen-Cilag, Novartis, Sanofi, and Takeda. JB received research funding from AbbVie, Acetylon, Amgen, Bluebird Bio, Bristol Myers Squibb, Celgene, Celularity, CRISPR Therapeutics, EMD Serono, Genentech, GlaxoSmithKline, Ichnos Sciences, Incyte, Janssen, Lilly, Novartis, Poseida, Sanofi, Takeda, and Teva; and consultancy fees from Bluebird Bio, Bristol Myers Squibb, Celgene, CRISPR Therapeutics, Janssen, Kite Pharma, Legend Biotech, Secura Bio, and Takeda. JLK has received grant funding from Bristol Myers Squibb, AbbVie, Bristol Myers Squibb, Celgene, Fortis Therapeutics, Genentech, Janssen, Sanofi Genzyme, and Sutro Biopharma; and personal fees from AbbVie, Bristol Myers Squibb, Celgene, Genentech, Incyte, Janssen, Pharmacyclics, Sanofi Genzyme, Tecnofarma, and TG Therapeutics. AG and MPM are employees of Bristol Myers Squibb. SL received research support from Bristol Myers Squibb, Celgene, Janssen, and Takeda; served on advisory boards for AbbVie, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Novartis, and Takeda; and was a member of the board of directors for TG therapeutics. KW received grant funding from Celgene, Amgen, Celgene, Janssen, and Sanofi; and personal fees from AbbVie, Amgen, Adaptive Biotech, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Oncopeptides, Roche, Sanofi, and Takeda; and non-financial support from Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Sanofi, and Takeda. All other authors declare no competing interests.