Elotuzumab With Lenalidomide and Dexamethasone in Newly Diagnosed Multiple Myeloma

The study aimed to evaluate the effectiveness of Elotuzumab combined with lenalidomide and dexamethasone in improving progression-free and overall survival for newly diagnosed multiple myeloma patients ineligible for HSCT. ELOQUENT-1 was a phase 3 clinical trial conducted in 19 countries at 185 healthcare facilities, including oncology practices and research centers. The study enrolled patients 18 years or older diagnosed with untreated, symptomatic myeloma, who were not eligible for high-dose therapy plus HSCT, and had an ECOG performance status of 2 or lower. Using an interactive voice response system, the trial randomly allocated patients in a 1:1 ratio to receive either elotuzumab with lenalidomide and dexamethasone or lenalidomide and dexamethasone. The randomization was stratified by the patient’s ISS (ISS; stage I-II vs. III), age(<75 years vs ≥75 years), and ECOG performance status(0 vs 1-2). Patients in the elotuzumab group received the drug intravenously at a dosage of 10 mg/kg on specific days during cycles 1 and 2: 10 mg/kg on days 1, 8, 15, and 22; cycles 3 and 18: days 1 and 15; and cycles after that: 20 mg/kg on day 1. Patients in both treatment groups received 40 mg of dexamethasone on days 1, 8, and 15 of each cycle and 25 mg of lenalidomide orally on days 1 through 21 of each cycle. The study’s primary endpoint was progression-free survival, and the results were based on the intention-to-treat population, as per the European Society for Blood and Marrow Transplantation criteria. The trial has been completed and registered with ClinicalTrials.gov under the identifier NCT01335399.

From August 4, 2011, to June 19, 2014, 748 patients were randomly assigned to either receive elotuzumab plus lenalidomide and dexamethasone treatment (374 patients) or lenalidomide and dexamethasone treatment (374 patients). Of these, 742 patients received treatment, with 333 (90%) of 371 patients in the elotuzumab plus lenalidomide and dexamethasone group and 339 (91%) of 371 patients in the lenalidomide and dexamethasone group discontinued treatment. The median age of the patients was 73.0 years (interquartile range [IQR] 69.0-78.0), and 294 (39%) patients were 75 years or older. The majority of the patients were male (412 [55%]) and White (711 [95%]). After a minimum follow-up of 65.3 months, there was no significant difference in the median progression-free survival between the two treatment groups, with 31.4 months (95% confidence interval [CI] 26.2-36.8) in the elotuzumab plus lenalidomide and dexamethasone group compared to 29.5 months (23.5-34.3) in the lenalidomide and dexamethasone group (hazard ratio [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, occurring in 64 (17%) of 371 patients in the elotuzumab plus lenalidomide and dexamethasone group compared to 79 (21%) of 371 patients in the lenalidomide and dexamethasone group. Study drug toxicity was the reported cause of death in five (1%) patients in the elotuzumab plus lenalidomide and dexamethasone group and four (1%) patients in the lenalidomide and dexamethasone group.

Source:https://pubmed.ncbi.nlm.nih.gov/35550060/

Clinical Trial: https://clinicaltrials.gov/study/NCT01335399

Dimopoulos MA, Richardson PG, Bahlis NJ, Grosicki S, Cavo M, Beksaç M, Legieć W, Liberati AM, Goldschmidt H, Belch A, Magen H, Larocca A, Laubach JP, Petrucci MT, Reece D, White D, Mateos MV, Špička I, Lazaroiu M, Berdeja J, Kaufman JL, Jou YM, Ganetsky A, Popa McKiver M, Lonial S, Weisel K; ELOQUENT-1 investigators. 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 Jun;9(6):e403-e414. doi: 10.1016/S2352-3026(22)00103-X. Epub 2022 May 9. PMID: 35550060.