Panelists discuss how managing a high-risk patient aged 64 years who progressed after 11 months on talquetamab with decreased B-cell maturation antigen (BCMA) surface expression presents challenging options, including switching to GPRC5D-targeting agents like talquetamab, pursuing clinical trials, or potentially using sequential bispecifics despite T-cell exhaustion concerns, while noting that the MonumenTAL-1 trial’s prior BCMA-directed therapy cohort showed promising 12-month progression-free survival, although the data are confounded by intervening therapies between treatments.