Be cautious to adopt a second CAR T-cell infusion after failure of CD19/CD22 cocktail CAR T-cell therapy in relapsed/refractory B-NHL

Chimeric antigen receptor (CAR) T-cell infusion (CTI) therapy has emerged as a breakthrough therapy in relapsed/refractory B-cell non-Hodgkin's lymphoma (R/R B-NHL), but a substantial number of patients still suffer treatment failure. Data on disease history, subsequent salvage therapies, and outcomes of patients who face treatment failure after the first CTI (CTI1) have not been reported in detail or systematically studied. Here, a retrospective analysis was performed on a total of 61 R/R B-NHL patients in whom salvage therapies were adopted after CTI1 treatment failure, with their clinical characteristics, subsequent management and outcomes described in detail. The results suggested that second-time CTI (CTI2) used as salvage therapy after failure of CTI1 could achieve a better transient overall response rate (ORR) than other salvage treatments (non-CTI2) in only a minority of patients (8/27 vs. 2/34, P=0.014). Nevertheless, the non-CTI2 group showed better event-free survival (EFS) (P = 0.007) and overall survival (OS) (P = 0.048) than the CTI2 group, with a median follow-up of 6.7 months vs. 4.7 months. In addition, univariate and multivariate analyses showed that only the status of the tumor at disease onset was an independent risk factor for survival; salvage therapy after CTI1 treatment failure was not. The adverse effects of CTI2 treatment were generally similar to those of non-CTI2 treatment, but the infection-related mortality was considerably higher. In conclusion, the prognosis of patients who fail CTI1 therapy is very poor regardless of the subsequent salvage therapies, and clinicians should be cautious about adopting CTI2 treatment after failure of treatment with the CD19/22 cocktail CTI1 in R/R B-NHL. Large-scale prospective studies are warranted, and new strategies are urgently needed to prevent treatment failure and improve the survival of B-cell lymphoma patients in future.