Case Report: Compromised response of memory-formed bystander T cells after CD19 CAR-T cell therapy following CD20 bispecific antibody therapy

T-cell redirection using chimeric antigen receptor (CAR)-T cells and/or bispecific antibody (BsAb) has been recognized as a new therapeutic option for relapsed/refractory large B-cell lymphoma. Bystander T cells in the body can affect immune responses after the treatment; however, their memory T-cell characteristics and antigen-specific responses still remain undefined. Here, we focused on memory-formed bystander T cells, and considered their viral-specific responses in a relapsed/refractory diffuse large B-cell lymphoma patient who developed adenoviral hemorrhagic cystitis as an uncommon complication after CD19 CAR-T cell therapy following CD20 BsAb therapy. After BsAb therapy, effector memory T cells were the predominant population in the patient's peripheral blood, achieving a complete response without unwanted viral infection. Although memory T-cell phenotypes remained unchanged for 8 weeks after pausing of BsAb therapy, it was found that bystander central/effector memory T cells had newly and successfully developed in the peripheral blood after sequential CAR-T cell therapy. Importantly, this patient did not develop any common viral infections during the course of treatment, such as reactivation of cytomegalovirus; however, adenoviral cystitis occurred even in the presence of memory T cells in the periphery after CAR-T cell therapy but not during BsAb therapy. These findings appear to suggest a difference between memory T-cell responses during BsAb therapy and those following CAR-T cell therapy, providing an important opportunity to reconsider memory-formed but newly-developed bystander T cells and their antigen-specific T-cell responses after CAR-T cell therapy.