Elotuzumab, an immunostimulatory monoclonal antibody, was recently approved by the US Food and Drug Administration for the treatment of patients with RRMM. Elotuzumab has a dual mechanism of action, directly activating natural killer cells and initiating antibody-dependent, cell-mediated cytotoxicity targeted against myeloma cells, with minimal effect on normal tissues.
In the 2-year analysis of the phase 3 ELOQUENT-2 study, patients with relapsed/refractory multiple myeloma and 1 to 3 prior therapies were randomized 1:1 to elotuzumab plus lenalidomide/dexamethasone or lenalidomide/dexamethasone in 28-day cycles until their disease progressed or their toxicities limited further treatment. Primary end points were progression-free survival and overall response rate. Secondary and other end points included overall survival and health-related quality of life, as measured by assessing worst pain using the Brief Pain Inventory–Short Form (BPI-SF).
A total of 646 RRMM patients were randomized to 1 of the 2 treatment arms. Patients’ median age was 66 years (20% ≥75 years), 32% of patients had a 17p deletion, 10% had a t(4;14) mutation, the median prior number of therapies was 2, and 35% of patients were refractory to their last therapy.
The elotuzumab-containing regimen resulted in a significant 30% reduction in the risk for disease progression or death versus lenalidomide/dexamethasone (hazard ratio, 0.70; 95% confidence interval, 0.57-0.85; P = .0004); the addition of elotuzumab to lenalidomide/dexamethasone was well tolerated, with minimal added toxicity.
Grade 3-4 adverse events occurred in ≥15% of patients as follows:
|Adverse event (Grade 3 or 4)||Elotuzumab + lenalidomide/dexamethasone (n = 321)||Lenalidomide/dexamethasone (n = 325)|
|Lymphopenia||78% (n = 250)||49% (n = 159)|
|Neutropenia||35% (n = 112)||44% (n = 143)|
|Anemia||20% (n = 64)||21% (n = 68)|
|Thrombocytopenia||21% (n = 67)||20% (n = 65)|
Infections (any grade) occurred in 83% of patients in the elotuzumab plus lenalidomide/dexamethasone arm and 75% in the lenalidomide/dexamethasone arm. Infusion reactions (mostly grade 1-2) occurred in 11% of patients treated with elotuzumab plus lenalidomide/dexamethasone. With regard to patient-reported pain (BPI-SF), sustained improvement in worst pain was observed in patients who showed a clinically meaningful response to treatment, with more patients demonstrating sustained improvement in the elotuzumab plus lenalidomide/dexamethasone arm (n = 74) versus the lenalidomide/dexamethasone arm (n = 56).
These findings led investigators to conclude that the addition of elotuzumab to lenalidomide resulted in an effective and durable benefit, with minimal incremental toxicities associated with the addition of elotuzumab. Future studies will provide insight into the long-term benefits of elotuzumab plus lenalidomide/dexamethasone combination therapy.