Despite recent advances, multiple myeloma remains an incurable disease for most patients, and initial remission will be followed by relapses requiring therapy. For many, there will be several remissions and relapses until resistance develops to all available therapies. With the introduction of several new agents, myeloma treatment has changed drastically, and there are new options for the management of relapsed or refractory disease, including new drug classes with distinct mechanisms of action and cellular therapies. However, resistance to major drug classes used in first-line remains the most critical factor for the choice of treatment at relapse. Continuous lenalidomide-based therapy is used extensively at first-line, and resistance to lenalidomide has become the key factor for the choice of salvage therapy. Daratumumab is increasingly used in first-line, and soon patients that relapse while on daratumumab will become a common challenge. Three-drug regimens are the standard approach to manage relapsed disease. Adding drugs with new mechanisms of activity can improve outcomes and overcomes class resistance, but, until now, while biology is important, it can offer only limited guidance for the choice of therapy.
© 2022 by The American Society of Hematology.