Cytomegalovirus–Cell‐Mediated Immunity Assays for the Prevention and Management of Cytomegalovirus in Transplant Recipients and Patients Receiving Cellular Therapies

CMV cell–mediated immunity (CMV–CMI) testing has emerged as a promising tool to refine CMV risk stratification and inform prevention strategies in transplant recipients, while recent data assess its role in novel cellular therapies. By identifying patients with robust CMV‐specific immune responses, these assays can reduce unnecessary antiviral exposure and support individualized decisions on prophylaxis and preemptive therapy. The strongest evidence comes from the solid organ transplant (SOT) setting, where immune‐guided strategies can safely shorten prophylaxis duration, particularly in kidney and lung transplantation. In allogeneic hematopoietic cell transplant (HCT) recipients, CMV–CMI could also guide prophylaxis discontinuation and post‐prophylaxis surveillance, although data remain more limited and its added value beyond established clinical markers unclear. In chimeric antigen receptor (CAR)‐T‐cell therapy recipients, CMV–CMI reaches a nadir at Week 2 post‐infusion and recovers by Week 4, defining a window of increased vulnerability during which most CMV reactivation occurs. Assessment at this timepoint may help identify high‐risk patients; however, the clinical impact of CMV reactivation, and as a result the need for preventive strategies, remain unclear in this setting. Importantly, the major strength of CMV–CMI lies in its consistently high negative predictive value of robust T‐cell responses, while its ability to pinpoint highest‐risk patients remains limited. Its widespread use is hindered by assay discordance, limited geographic access, and unproven cost‐effectiveness. Despite these limitations, CMV–CMI remains the best‐studied strategy for individualized CMV management; further standardization and prospective validation are needed to define its role in increasingly complex immunocompromised populations. image