Pseudoprogression After Axi-cel in Primary Refractory PMBCL Following Failed Bridging: Case Report and Management Considerations

Primary mediastinal large B-cell lymphoma (PMBCL) is a rare, aggressive lymphoma with limited therapeutic options in the relapsed or refractory setting. Axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, has shown promising efficacy; yet treatment decisions remain challenging in patients with rapidly progressive disease and high tumor burden. We report a 29-year-old woman with primary chemotherapy-refractory PMBCL who developed fulminant extranodal disease progression despite radiotherapy and systemic bridging therapy (BT) prior to planned axi-cel infusion. Following CAR T-cell therapy, she experienced grade 2 cytokine release syndrome (CRS) and grade 3 immune effector cell–associated neurotoxicity syndrome (ICANS), alongside clinical deterioration and radiological findings suggestive of disease progression. Notably, pronounced CAR T-cell expansion preceded biochemical improvement and subsequent radiological tumor regression, consistent with pseudoprogression rather than true treatment failure. Despite initially misleading clinical and imaging findings in the context of suboptimal baseline conditions, the patient achieved a durable complete remission and remains disease-free 23 months post-CAR T-cell therapy, with excellent quality of life. This case highlights the critical importance of recognizing immune-mediated flare phenomena to guide clinical decision-making and avoid premature treatment discontinuation or misclassification of therapeutic failure.