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The definition of double-refractory disease is evolving over time, and can vary from country to country, says Maria-Victoria Mateos, MD, PhD. The classical definition refers to patients refractory to bortezomib and thalidomide and/or lenalidomide—the first generation proteasome inhibitors and immunomodulatory agents (IMiDs). With the availability of second-generation proteasome inhibitors and IMiDs, the challenge is, says Mateos, finding new agents with different mechanisms of action for this heavily pretreated population.
A whole range of options are emerging for patients with multiple myeloma, states Andrew Spencer, MD. There is a great deal of excitement regarding the use of monoclonal antibodies, such as elotuzumab and anti-CD38 antibodies, and with epigenetic modifying agents, in multiple myeloma, he adds. Panobinostat, a histone deacetylase (HDAC) inhibitor, was recently approved in the United States and in Europe. The available evidence suggests that HDAC inhibitors also have the potential to be combined with other agents, notes Spencer.