Transformation to Plasmablastic Lymphoma Following CD19-Directed CAR T Cell Therapy for Refractory Diffuse Large B...

Plasmablastic lymphoma is a rare, aggressive large B cell lymphoma characterized by plasmablastic morphology, terminal B cell (plasma cell) differentiation, frequent loss of conventional B cell markers, and poor clinical outcomes. Although classically associated with immunodeficiency and Epstein-Barr virus (EBV) infection, plasmablastic lymphoma has also been described as an uncommon mechanism of relapse after CD19-directed chimeric antigen receptor T cell (CAR-T) therapy. We report a 69-year-old man with a remote history of chronic lymphocytic leukemia/small lymphocytic lymphoma and subsequent refractory diffuse large B cell lymphoma (DLBCL) who developed rapidly progressive, CD19-negative plasmablastic lymphoma approximately 1 month after CD19-directed CAR-T therapy. Although DLBCL was of a nongerminal-center phenotype with expression of pan-B markers including CD19 and lack of CD138, the post-CAR-T transformed lymphoma demonstrated acquisition of plasmablastic morphology and CD138 expression, loss of pan-B markers and negative for EBV by in situ hybridization and HHV8 by immunostaining. Fluorescence in situ hybridization (FISH) on the plasmablastic lymphoma showed a MYC::IGH fusion and low-level MYC copy gain that were absent in the antecedent DLBCL. Disease dissemination was later confirmed on left pleural fluid cytology a few days before the patient passed away. This case highlights EBV and HHV8 negative plasmablastic transformation as a rare but important post-CAR-T relapse pattern and underscores the need for repeat biopsy, comprehensive paired immunophenotyping, and molecular studies in patients with atypical progression after cellular therapy.