Overall survival was significantly improved when elotuzumab was added to pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma previously treated with lenalidomide and proteasome inhibitors
Survival outcomes were significantly improved when elotuzumab (Ninlaro) plus pomalidomide (Pomalyst)/dexamethasone was given to patients with relapsed/refractory multiple myeloma who have previously been treated with lenalidomide (Revlimid) and a proteasome inhibitor vs pomalidomide/dexamethasone alone, according to final OS findings from the phase 2 ELOQUENT-3 trial (NCT02654132) published in the Journal of Clinical Oncology.
In patients given the triplet regimen, the median overall survival (OS) was 29.8 months (95% CI, 22.9-45.7) compared with 17.4 months (95% CI, 13.8-27.7) in the doublet regimen arm (HR, 0.59; 95% CI, 0.37-0.93; P = .0217). At 1-year, the OS rates were 79% vs 68%, 63% vs 44% at 2 years, and 39% vs 29% at 3 years in the triplet and doublet arms, respectively.
A total of 60 patients were randomly assigned to the elotuzumab plus pomalidomide/dexamethasone arm and 57 to the pomalidomide/dexamethasone arm. Patients received a median of 3 previous lines of therapy, with 68.3% of patients in the triplet arm being refractory to lenalidomide and a proteasome inhibitor vs 71.9% in the doublet arm.
Treatment discontinuation occurred in 96.7% of patients in the triplet arm vs 98.2% in the doublet arm. The main reason for discontinuation was disease progression including 70.0% of those in the triplet arm vs 70.9% in the doublet arm. Of the patients receiving the triplet regimen, 80.0% reached a relative dose intensity (RDI) of 90% or higher with elotuzumab. Moreover, pomalidomide was well balanced with 51.7% vs 49.1% having achieving an RDI of 90 or more. Among the 93 patients 75 years or younger, RDI of 90 or more was achieved in 40.8% vs 45.5%, and in those older than 75, 63.6% vs 54.5% of those in the triplet and doublet arms, respectively, achieved an RDI of 90 or more.
The minimum follow-up was 45 months, with 78 deaths occurring during that time. Disease progression was the most common cause of the death with 41.7% of patients dying in the elotuzumab plus pomalidomide/dexamethasone group vs 49.1% in the pomalidomide/dexamethasone group.
The subgroup analysis showed similar OS results across both arms. The median OS for patients 75 or older in the triplet arm was 34.4 months vs 14.7 months in the doublet arm (HR, 0.36; 95% CI, 0.13-1.01). For those who were refractory to lenalidomide and a proteasome inhibitor, the median OS was 28.3 months vs 17.4 months in each respective group (HR, 0.74; 95% CI, 0.44-1.25). Those who were refractory to 4 or more lines of prior therapy, the median OS was 29.8 months in the triplet arm vs 16.0 months in the doublet arm (HR, 0.42; 95% CI, 0.20-0.89). Among those who received lenalidomide as their most recent line of therapy, the median OS was 32.0 months vs 20.8 months in each arm, respectively (HR, 0.55; 95% CI, 0.29-1.04). In patients who had received prior stem-cell transplant, the median OS was 26.6 months vs 27.7 months (HR, 1.05; 95% CI, 0.58-1.90) for patients in the elotuzumab plus pomalidomide/dexamethasone and pomalidomide/dexamethasone arm, respectively.
Anemia was the most common adverse effect (AE) of any grade with 28.3% of patients experiencing it in the triplet arm and 38.2% in the doublet arm, as well as neutropenia which occurred 26.7% vs 30.9% of patients, respectively. Grade 3/4 AEs that were most common included neutropenia (15.0% vs 27.3%) and anemia (11.75 vs 21.8%) in the triplet and doublet arms, respectively. In the triplet arm, 70.0% of patients experienced serious AEs vs 60.0% in the doublet arm, the most common of which were respiratory tract infection (8.3% vs 5.5%) and pneumonia (6.7% vs 9.1%). In the elotuzumab plus pomalidomide/dexamethasone arm, 70.0% of patients experienced infections vs 65.5% in the pomalidomide/dexamethasone arm, of which 25.0% vs 21.8%, respectively, were grade 3/4.
In relation to study treatment, the most common any-grade AEs were neutropenia (20.0% vs 21.8%), and hyperglycemia (20.0% vs 12.7%) in the triplet and doublet arms, respectively. Secondary primary malignancies such as prostate cancer, pancreatic adenocarcinoma, and basal cell carcinoma occurred in 6.7% of patients in the triplet arm, with 3.6% of patients in the doublet arm experiencing cholangiocarcinoma or invasive breast carcinoma.
Grade 1/2 infusion-related reactions occurred in 2 patients during the first treatment cycle. Treatment discontinuation because of AEs occurred in 18.3% of patients in the elotuzumab plus pomalidomide/dexamethasone arm and 23.6% in the pomalidomide/dexamethasone arm, while 11.7% of patients and 10.9% discontinued because of grade 3/4 AEs.
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. J Clin Oncol. Published online August 12, 2022. doi:10.1200/JCO.21.02815