The Evolution of Chimeric Antigen Receptor T-Cell, Bispecific Antibodies and Antibody–Drug Conjugates for the Treatment of Multiple Myeloma

Modern immunotherapies are reshaping the treatment landscape of multiple myeloma (MM), offering the possibility of deeper responses and prolonged survival. Over the past 5 years, chimeric antigen receptor (CAR) T-cell therapies, bispecific antibodies (BsAb), and antibody-drug conjugates have been developed and approved, first in the relapsed/refractory MM setting and progressively in earlier lines of therapy, underscoring a shift toward their use across the entire disease course, including at diagnosis. Concurrently, novel therapeutic constructs, such as trispecific antibodies, dual-target CAR T-cells, and combinations of different T-cell-redirecting therapies or their integration with standard agents, are currently under investigation across the entire treatment landscape. Despite their remarkable efficacy, these therapies are associated with distinct and clinically relevant toxicities that require careful understanding and management. These include well-recognized adverse events associated with CAR T-cell therapies and BsAb, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as an increased risk of infections, additional neurologic complications, and the ocular toxicity observed with belantamab mafodotin. In this review, we discuss the efficacy and safety profiles of CAR T-cell therapies, BsAb, and belantamab mafodotin within the current MM treatment landscape, highlighting evidence from both clinical trials and real-world studies, and providing an overview of available data on therapeutic sequencing strategies.