Use of elotuzumab with conventional therapy linked to improved survival in multiple myeloma patients

1. Adding elotuzumab to the conventional lenalidomide and dezamethasone was associated with a 30% reduction in the risk of disease progression or death in relapsed or refractory multiple myeloma (MM) patients.

2. The clinical benefit appears to be greater in patients with a higher burden of disease. Further investigations are warranted.

Evidence Rating Level: 1 (Excellent)      

Study Rundown: Most patients with MM have a relapse and overall survival is approximately 5 years. Lenalidomide and dexamethasone are used in combination as a standard regiment in patients with relapsed or refractory disease. Elotuzumab is a first-in-class humanized immunoglobulin G1 immunostimulatory antibody that enables selective killing of myeloma cells while minimally effecting healthy tissue. Three drug combination therapies are becoming more popular for treatment of MM but toxic side effects may be cause for limited use. A phase 2 trial used a combination of elotuzumab with lenalidomide and dexamethasone with promising results.

This phase 3 randomized controlled trial, called ELOQUENT-2 specifically evaluated whether using a three drug combination of elotuzumab, lenalidomide, and dexamethasone together instead of lenalidomide and dexamethasone alone was efficacious and safe. A total of 646 participants from 168 sites underwent randomization. At the 2 year follow-up, the rate of progression-free survival was significantly higher in the combination group. Subgroup analyses showed that the greatest benefit in progression-free survival occurred among patients that had been diagnosed with MM for 3.5 years or more with a median survival of 26 months. There were no significant differences between the two groups in overall health-related quality of life.

Click to read the study, published today in NEJM

Relevant Reading: Lenalidomide plus Dexamethasone for Relapsed or Refractory Multiple Myeloma

In-Depth [randomized controlled trial]: This was a phase 3, open-label, multicenter trial. 646 participants were randomly assigned in a 1:1 ratio to receive either the combination of elotuzumab with lenalidomide and dexamethasone or receive the traditional therapy of lenalidomide and dexamethasone regimen group. There were no significant differences between the two groups for baseline patient characteristics. The rate of progression-free survival in the combination group was higher at the 1 year and the 2 year follow-ups (68% vs. 57% and 41% vs. 27%, respectively). The median progression-free survival was significantly higher in the combination group compared to the control (19.4 months vs. 14.9; HR = 0.70; 95% CI, 0.57 – 0.85; p<0.001). Therefore participants showed a 30% reduction in the risk of disease progression or death as compared with the control group. This benefit was observed in a subgroup analysis of patients that were 65 years of age or older, those with resistance to most recent line of therapy, with prior exposure to borezomib/immunomodulatory drugs, with prior stem cell transplantation, with the del(17p) variant, or with a creatinine clearance of <60ml/min. The greatest benefit was observed among participants whom MM had been diagnosed ≥3.5 years prior to recruitment (HR=0.55; 95% CI, 0.44 – 0.70; p<0.001). There were no significant effects on patients’ pain or health-related quality of life in the combination group.

In this study, more than 1/3 of the participants had resistance to prior therapy including bortezomib or thalidomide. The study had a higher proportion of patients (30%) that had a high-risk cytogenic profile (defined as positive results for t(4;14) or t(14;16) or at least 60% cells with del(17p).

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