Emerging Concepts in the Treatment of Multiple Myeloma - Episode 1

Introduction: Monoclonal Antibodies in Multiple Myeloma

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The phase III ELOQUENT-1 and -2 trials are assessing the use of lenalidomide plus dexamethasone with or without elotuzumab as a treatment for patients with multiple myeloma in the newly diagnosed and relapsed/refractory setting. In the ELOQUENT-2 trial, the elotuzumab triplet demonstrated a higher response rate compared with lenalidomide and dexamethasone alone, which has translated into a 30% reduction in the risk of disease progression for individuals with relapsed/refractory multiple myeloma, says Noopur Raje, MD.

In findings presented at the 2015 ASCO Annual Meeting from the ELOQUENT-2 study, the median progression-free survival (PFS) with the elotuzumab regimen was 19.4 months versus 14.9 months with lenalidomide and dexamethasone alone (HR = 0.70; P = .0004). The objective response rate (ORR) was 79% with elotuzumab versus 66% in the control arm (P = .0002). Overall survival (OS) data for the trial are not yet mature.

This is a new milestone in multiple myeloma, comments Raje, noting that monoclonal antibodies can be piggybacked on any combination approach in myeloma once adverse events, such as infusion reactions, are managed. In the study, 10% of patients receiving elotuzumab experienced infusion reactions, the majority of which were grade 1/2 and manageable.

In addition to the ELOQUENT-2 study, the ongoing phase III ELOQUENT-1 trial is examining the elotuzumab plus lenalidomide and dexamethasone regimen in the frontline setting for relapsed/refractory multiple myeloma. Additionally, other monoclonal antibodies are also being explored for patients with multiple myeloma, including daratumumab, an anti-CD38 antibody.

In a phase II trial, single-agent daratumumab showed double-digit response rates in patients with heavily pretreated multiple myeloma, states Jatin J. Shah, MD. In this study, the ORR was 29.2% and the 1-year OS rate was 65%. The duration of response of 7.4 months and PFS of 3.7 months confirms that daratumumab has high single-agent activity, says Heather J. Landau, MD. Patients in this study had received a median of 5 prior therapies over a median of 4.8 years.

With the availability of these very effective agents, the question going forward will be how to fit them into induction, consolidation, and maintenance strategies for patients with multiple myeloma, says Morie A. Gertz, MD. An added benefit is that monoclonal antibodies are not associated with as much toxicity as other options. Given the data presented thus far, it seems likely that monoclonal antibodies will move quickly to the frontline because of their ability to combine well with treatments without adding additional toxicity, suggests Rafael Fonseca, MD.