Emerging Therapies in Multiple Myeloma

A large proportion of patients with multiple myeloma have activating mutations in the Ras/MAP kinase pathway, which provides a strong rationale to examine the use of agents that are inhibitors along this pathway, states Andrew Spencer, MD. Another pathway that is important in multiple myeloma is the PI3K/Akt pathway, he adds. There is preclinical evidence that Akt inhibitors can be effective in this disease, and these targeted agents need to be fully explored, perhaps with a proteasome inhibitor/immunotherapy backbone, to better determine which patients are most likely to benefit from them, Spencer notes.

Ixazomib is a second-generation oral proteasome inhibitor that has been evaluated for the treatment of relapsed and refractory patients with multiple myeloma. Data have shown ixazomib to be effective even in patients previously treated with bortezomib, lenalidomide, and other second-generation proteasome inhibitors, remarks Maria-Victoria Mateos, MD, PhD. The agent is also being evaluated in newly diagnosed patients and as a maintenance therapy, she adds.

There are two monoclonal antibodies that have shown promise in multiple myeloma, notes Jatin J. Shah, MD. In the phase III ELOQUENT trials, elotuzumab, which targets SLAM7, showed activity in combination with lenalidomide and dexamethasone in both newly diagnosed and relapsed/refractory patients. Daratumumab, which targets CD38, has efficacy in combination with lenalidomide and dexamethasone, and as monotherapy in later-line settings. These two agents work in different ways, adds Shah, and have the potential to be practice-changing.