CAR-T and Bispecific Antibodies: The New Standard for Relapsed and Refractory Multiple Myeloma, or Reserved for Late-Line Salvage Therapy?

The treatment of relapsed and refractory multiple myeloma has improved substantially in the last 5–10 years based on the development and use of several novel classes of drugs and drug combinations. These advances have led to improvements in progression-free and overall survival as well as quality of life. The general tendency has been to advance drugs/combinations that have performed well in advanced disease to the earlier line settings (frontline, first/early relapse). There are several triplet drug combinations that, when used as part of first or early relapse, can provide remission durations of 3 years or longer. More recently, impressive responses have been seen with the use of targeted immunotherapeutics (chimeric antigen receptor T-cells and bispecific antibodies) in heavily pretreated patients with MM. These treatments, however, have been associated with some new and occasionally severe toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and severe infections, including opportunistic infections and profound cytopenias. These potential toxicities bring into question whether these immune-targeting drugs should remain as late-line therapeutics or whether the high single-agent overall response rates mandate that these agents be used in earlier line settings. Herein, the authors provide a point and counterpoint about the future use of these agents.