Second-Generation Agents in Relapsed Multiple Myeloma

Agents used to treat relapsed multiple myeloma include bortezomib, a first generation proteasome inhibitor, and lenalidomide, an early immunomodulatory drug (IMiD), states Kenneth Anderson, MD. The second-generation of agents approved for treatment of relapsed disease include pomalidomide, a new IMiD, and carfilzomib, a new proteasome inhibitor with a greater depth and duration of proteasome inhibition than its predecessor bortezomib, adds Anderson. Additionally, in February 2015, the first-in-class histone deacetylase (HDAC) inhibitor panobinostat was approved as a treatment for relapsed multiple myeloma.

Treatment history, whether the patient has high-risk disease, and the presence of comorbidities should be considered when selecting therapy, says Anderson. Lenalidomide and bortezomib are typically used first-line, while pomalidomide and carfilzomib are second-line treatment options. Panobinostat would likely be reserved for patients whose myeloma returns following several lines of therapy that may include pomalidomide or carfilzomib, explains Anderson. Panobinostat is a broad-acting HDAC that has a high level of activity even in relapsed/refractory disease, but is also associated with certain toxicities.

The phase III ENDEAVOR trial compared bortezomib plus dexamethasone with carfilzomib, dose-escalated up to 56 mg/m², plus dexamethasone, in relapsed disease. The study demonstrated that progression-free survival was doubled in the carfilzomib arm (18.7 months) versus the bortezomib arm (9.4 months). ENDEAVOR demonstrated that carfilzomib is very active in the relapsed setting and was well-tolerated, says Anderson. More recent data, adds Anderson, has suggested a high level of response with carfilzomib earlier in the disease course.