The extended 4-year follow-up results of the ELOQUENT-2 trial

Multiple myeloma is the second most common hematologic malignancy accounting for approximately 18% of all hematologic malignancies in the United States in 2016 [1]. Although the introduction of proteasome inhibitors and immunomodulatory agents in the treatment landscape of the disease has significantly improved the patients outcomes and has extended overall survival, multiple myeloma still remains incurable and all patients will eventually relapse. Therefore, the need for novel and effective therapeutic strategies is more than imperative. Under this prism, agents with novel mechanisms of action are combined with the standard regimens in order to overcome the drug resistance phenomenon and provide deep and durable responses also reflecting an advantage in overall survival. Elotuzumab is a humanized IgG1 monoclonal antibody targeting the signaling lymphocytic activation molecule F7 (SLAMF7), which is expressed on myeloma cells and natural killer cells but not on normal tissues [2]. Elotuzumab has a dual mechanism of action, by causing directly myeloma cell death through activation of natural killer cells or via antibody-dependent cellular cytotoxicity [2, 3]. It was demonstrated that the combination of elotuzumab with lenalidomide and dexamethasone (EloRd) further enhanced the activation of natural killer cells and subsequent myeloma cell death [4]. This triplet combination was evaluated in the randomized phase 3 ELOQUENT-2 trial compared to lenalidomide-dexamethasone (Rd) in patients with relapsed/refractory multiple myeloma (RRMM) who had received 1 to 3 prior lines of therapy and had documented disease progression after their most recent therapy [5]. The primary endpoints were progression free survival (PFS) and overall response rate (ORR). Overall survival (OS) was a secondary endpoint, while other exploratory endpoints included duration of response and safety. In previous analyses of the study at 2 and 3 years follow up, EloRd reduced the relative risk of disease progression or death by 30% and 27% respectively [5,6]. Among patients receiving the triplet combination the PFS rates demonstrated sustained relative improvements of 52% and 44% at 2 and 3 years respectively [5,6]. It was also demonstrated that the greatest PFS benefit was in favor of patients with a time from diagnosis longer or equal to the median of 3.5 years and especially for those with 1 prior line of therapy [5, 6]. These data probably indicate that slow progressors may particularly benefit from the addition of elotuzumab to Rd. Based on the survival benefit observed with elotuzumab