Outcome after chimeric antigen receptor (CAR) T‐cell therapy failure in large B‐cell lymphomas

Summary This study retrospectively evaluated the outcome of salvage therapy in 51 patients who failed axicabtagene ciloleucel or tisagenlecleucel for relapsed/refractory large B‐cell lymphomas. Of these patients, 22 (43%) were enrolled in clinical trials (glofitamab or loncastuximab tesirine + ibrutinib), whereas 29 received standard therapies (lenalidomide [Len], checkpoint inhibitors [CPIs], ibrutinib [I], chemoimmunotherapy and radiotherapy) or supportive care. Overall, 26 of 39 (67%) treated patients received a treatment based on immunotherapy (glofitamab, CPI, Len) that was mainly represented by bispecific antibody ( n = 18). In this subgroup, plasma samples were collected and analysed for circulating tumour DNA (ctDNA) using cancer‐personalized profiling by deep sequencing (CAPP‐seq). The study found that patients with high ctDNA had poor outcomes. At a median follow‐up of 11.7 months, the estimated 12‐month overall survival (OS) was 35%. Factors adversely affecting the prognosis in the multivariable model were the absence of response to CAR T‐cell therapy (HR: 3.08; p = 0.0109) and a diagnosis other than PMBCL and t‐FL (HR: 4.54; p = 0.0069). The outcome of patients failing CAR T cells is poor and requires further investigation.