Determinants of primary resistance to BCMA bispecifics in multiple myeloma. High levels of sBCMA, low BCMA surface abundance, unfavorable E:T ratios, suboptimal dosing, and baseline T-cell exhaustion collectively mediate primary refractoriness to BCMA×CD3 antibodies but may be unleashed by therapeutic intervention. CELMoDs, cereblon E3 ligase modulatory drugs; GSI, γ-secretase inhibition; IMiDs, immunomodulatory drugs. Professional illustration by Somersault18:24.