Beyond Remission: Risk-Adapted Maintenance and Mechanism-Guided Salvage After CAR T-Cell Therapy for Multiple Myeloma

B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy can induce deep responses in relapsed or refractory multiple myeloma, yet relapse remains frequent. Neither post-infusion maintenance nor salvage after CAR T-cell failure has an established standard.

This review synthesizes pivotal trials, real-world cohorts, and translational studies into a risk-adapted framework for longitudinal care. Relapse biology, target modulation, CAR T-cell persistence, immune reconstitution, measurable residual disease (MRD), and imaging are integrated to guide structured observation, time-limited maintenance, pre-emptive intervention, and salvage. Preventive treatment is defensible only when the estimated risk posed by residual disease exceeds the competing risks of infection, cytopenia, and delayed immune recovery. At relapse, treatment selection should begin with clinical tempo, disease compartment, contemporary expression of BCMA, G protein-coupled receptor class C group 5 member D (GPRC5D), and Fc receptor-homolog 5 (FcRH5), prior target pressure, and host immune fitness.

Structured observation is appropriate for many patients with sustained MRD negativity, no extramedullary disease, and recovering immune function. Persistent or rising MRD, residual lesions, aggressive disease biology, or unfavorable CAR T-cell kinetics should prompt early trial referral rather than automatic chronic therapy. Salvage may involve BCMA retargeting, a switch to GPRC5D or FcRH5, conventional cytoreduction, radiotherapy, antibody-drug conjugates, bispecific antibodies, or a second cellular platform. Future trials should assess progression-free survival together with infection-free survival, treatment-free interval, immune recovery, quality of life, and responsiveness to subsequent salvage.