Timing Referral, Holding Therapy, and Bridging Therapy Definitions

Timing referral for chimeric antigen receptor (CAR) T-cell therapy is critical when patients with multiple myeloma experience relapse or progressive disease. Doris Hansen, MD, and Prerna Mewawalla, MD, discuss referral in the setting of rising immunoglobulin light chains and a new lesion on imaging, emphasizing referral as early as possible, ideally at first relapse or sooner when a clinical trial may be appropriate. They explain that the timing of holding therapy depends on the pace of disease progression and whether a patient can safely wait for consultation and T-cell collection. Holding therapy is used between relapse and apheresis to stabilize disease while avoiding lymphotoxic treatments that could compromise T-cell manufacturing. Bridging therapy occurs after apheresis and before CAR T-cell infusion, when T-cell engagers can be used because the cells have already been collected. Talquetamab is discussed as a favored bridging option because it targets G-protein-coupled receptor class C group 5 member D (GPRC5D) rather than B-cell maturation antigen (BCMA). Alkylators remain another option, although cytopenias may occur.