Beyond Remission: Risk-Adapted Maintenance and Mechanism-Guided Salvage After CAR T-Cell Therapy for Multiple Myeloma
- 1Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China
Abstract
Background: 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.
Main Text: 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.
Conclusions: 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.
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BibTeX
@article{su2026beyond,
title = {{Beyond Remission: Risk-Adapted Maintenance and Mechanism-Guided Salvage After CAR T-Cell Therapy for Multiple Myeloma}},
author = {Shuai Su and Sijia Yan and Jiaying Wu and Yi Xiao},
journal = {Stem Cell Reviews and Reports},
year = {2026},
month = sep,
doi = {10.1007/s12015-026-11228-z},
url = {https://doi.org/10.1007/s12015-026-11228-z},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Beyond Remission: Risk-Adapted Maintenance and Mechanism-Guided Salvage After CAR T-Cell Therapy for Multiple Myeloma
AU - Shuai Su
AU - Sijia Yan
AU - Jiaying Wu
AU - Yi Xiao
PY - 2026
DA - 2026/09/02
JO - Stem Cell Reviews and Reports
DO - 10.1007/s12015-026-11228-z
UR - https://doi.org/10.1007/s12015-026-11228-z
AB - Background: 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. Main Text: 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. Conclusions: 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.
SN - 2629-3269
SN - 2629-3277
ER -