Abstract
Current treatment strategies have led to unpredictable improvements in the management of multiple myeloma (MM) over time. However, resistance to therapy, particularly regarding lenalidomide refractoriness and, more recently, daratumumab and lenalidomide refractoriness, even in the first-line setting, has become an increasingly significant issue in recent years. This resistance complicates the identification of the optimal treatment algorithm for patients with relapsed/refractory MM, particularly at first relapse. In this review, we focus on current strategies for MM patients progressing on or after lenalidomide-based and daratumumab-lenalidomide-based regimens. The forthcoming availability of next-generation immunotherapies, along with a deeper understanding of resistance mechanisms, is highly anticipated. Meanwhile, based on promising results from recent studies, the approval of novel drugs to expand the current therapeutic armamentarium against MM is bringing us closer to the goal of making a potential cure for the disease much more achievable in the hopefully near future.