There has been tremendous progress made in multiple myeloma in the last decade, resulting in improved overall survival for all patients, including those with high-risk disease and those ineligible for transplantation. However, despite the addition of several novel agents, unprecedented response rates, and our ability to achieve complete remission in the majority of patients, the disease remains incurable in nearly all and will require repeated therapies. With many options available to the clinician, there is no simple or ideal sequence of treatments that has been established, so the choice of relapsed therapy is based on a series of factors that include response and tolerability of prior therapies, risk status, available novel agents, aggressiveness of relapse, renal function, performance status, cost, etc. This chapter provides practical guidance in selecting relapsed therapies structured through a series of 5 questions that can inform the decision. Specific emphasis is placed on the 2 most recent novel agents, carfilzomib and pomalidomide, but agents in development are also included.
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