Ixazomib and Elotuzumab in Multiple Myeloma

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Proteasome inhibitors are an integral part of the treatment strategy for patients with multiple myeloma. The biggest challenge currently facing the utilization of these treatments is that patients must travel to the clinic to receive an infusion or subcutaneous injection, suggests Shaji Kumar, MD. To address this, a new proteasome inhibitor, ixazomib, was developed.

Ixazomib has been studied in the relapsed setting as a single agent and has been shown to be active in patients who had previously been on bortezomib. In this trial, 90% of newly diagnosed patients had a response to the combination of ixazomib with lenalidomide and dexamethasone. It was well tolerated, with skin rash and gastrointestinal side effects.

In addition to the well-established class of proteasome inhibitors, monoclonal antibodies are beginning to show promise as potential treatments for patients with multiple myeloma. The monoclonal antibody elotuzumab, which targets the SLAMF7 receptor on the surface of almost all plasma cells, was the first of this class of agent to be successfully introduced into clinical trials, Sagar Lonial, MD, states.

As a single agent in multiple myeloma, elotuzumab induced stabilization of disease. When combined with lenalidomide and low-dose dexamethasone, there was an 80% response rate. There are 2 large randomized phase III trials that have completed accrual, says Lonial. One of them is a relapsed trial of elotuzumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone. The other trial studies transplant-ineligible patients with newly diagnosed multiple myeloma.

One of the current drawbacks with elotuzumab is its long infusion times, suggests James R. Berenson, MD. To address this, the safety of a quicker infusion is currently being studied.