Autologous CD19 CAR T Cells(Marino Biotechnology)

In an article in this issue of the Journal, Kretschmann et al. present data on the preparation of anti-CD19 CAR T cells for use in systemic lupus erythematosus (SLE), thus expanding the potential applications of CAR T cells beyond B cell malignancies.SLE is an autoimmune disease that has remained an enigma, for which reliable and effective treatments are still unavailable.In that light, the current study by Kretschmann et al. provides important information given the patients′ previous therapy with immunosuppressive medications and concerns about chronic activation by autoantigens.Following trans- duction with an anti-CD19 CAR, whose components matched those of Tisagenlecleucel (Kymriah), and 12 days of in vitro expansion, sufficient CAR T cell product was recovered from each of the SLE patients to proceed with the CAR T cell administration.

CD28‐based CD19 chimaeric antigen receptor‐modified (CAR‐)Tcells were recently FDA‐approved for adult acute lymphoblastic leukaemia (ALL). We report long‐term outcome of 37 children and young adults treated with autologous CD19 CAR‐T cells. The complete remission rate was 86%, of which 71% were polymerase chain reaction (PCR) minimal residual disease (MRD)‐negative, 14% were MRD‐negative by flow cytometry, and 14% were PCR MRD‐positive. 26 patients proceeded to subsequent haematopoietic stem cell transplant (HSCT). 11 patients had a CD19‐postive relapse (eight post HSCT and three without) and one had a CD19‐negative relapse. All relapse events occurred within two years from cell therapy. With a median follow‐up of three years, the median event‐free survival (EFS) is 17 months and the median overall survival (OS) is not reached. The three‐year EFS is 41% and OS is 56%. Patients with >5% blasts in the bone marrow prior to lymphodepletion had an inferior EFS. All patients with a PCR MRD‐positive result at day 28 had relapsed after CAR‐T‐cell therapy. A prior HSCT did not significantly affect outcome, but a consolidative transplant after achieving remission improved long‐term results. Overall, prelymphodepletion disease burden and molecular MRD negativity following CAR‐T cells are predictors of long‐term outcome following CD19 CAR‐T‐cell therapy for ALL.