Mantle cell lymphoma transformation to CD19-negative classic Hodgkin lymphoma as a novel mechanism of escape from CD19 chimeric antigen receptor T cell therapy.

Mantle cell lymphoma (MCL) is a mature B cell neoplasm characterized by the CCND1::IgH t(11;14) translocation. The process of MCL clonal evolution remains poorly understood. In this report, we describe a rare case of a patient with blastoid variant MCL who developed clonally related classic Hodgkin lymphoma (CHL), following CD19 chimeric antigen receptor T cell (CAR T cell) therapy. A 65-year-old man was initially diagnosed with blastoid variant MCL with a concurrent TP53 deletion. He was treated with chemotherapy followed by CD19 CAR T cell therapy with significant clinical response. Eight months later, he developed a recurrence with numerous CD19-negative, pleomorphic cells with Hodgkin and Reed-Sternberg-like (HRS-like) phenotype. The previously described blastoid MCL component was eradicated. Fluorescence in situ hybridization (FISH) testing confirmed CCND1::IgH t(11;14) in the HRS-like tumor cells, indicating a clonal relationship to the original MCL. Loss of CD19 expression is a known mechanism of resistance in CD19 CAR T cell therapy in B cell lymphomas. A notable feature of the HRS-like cells in this case is the gain of markers associated with CHL, such as CD30 and CD15. This immunophenotypic shift highlights the concept of lymphoma plasticity, where the tumor cells evolve in response to selective pressures, such as CAR T cell therapy.