T-cell–redirecting bispecific antibodies represent a new standard of care for the treatment of triple-class refractory myeloma patients. Here, 2-[ 18 F]FDG PET/CT imaging was performed on a 61-year-old woman with relapsed myeloma to determine metabolic response to talquetamab, a GPRC5DxCD3-bispecific antibody. At day 28, monoclonal (M) component assessment confirmed very good partial response (97% monoclonal protein reduction), whereas 2-[ 18 F]FDG PET/CT imaging revealed early bone flare-up phenomena. At day 84, bone marrow aspirate, M-component assessment, and 2-[ 18 F]FDG PET/CT demonstrated complete response, confirming the early flare-up hypothesis.