How I treat relapsed multiple myeloma

Despite recent advances multiple myeloma remains an incurable disease for most of the 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 remain 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 standard approach to manage relapsed disease. Adding drugs with new mechanisms of activity can improves outcomes and overcomes class resistance but, until now, while the biology is important, can offer only limited guidance for the choice of therapy.