Donor- and patient-derived interleukin 6 knockdown CD19-targeted chimeric antigen receptor T cells exhibit similar efficacy and safety in treating relapsed B-cell acute lymphoblastic leukemia patients after allogeneic hematopoietic stem cell transplantation.
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BACKGROUND AIMS: Chimeric antigen receptor (CAR) T-cell therapy has significantly improved the prognosis of relapsed B-cell acute lymphoblastic leukemia (B-ALL) patients with recurrent disease after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, whether to use donor- or patient-derived CAR T cells has not yet been clarified. METHODS: This was a retrospective analysis to compare the efficacy and safety of donor- and patient-derived super and safe CD19-targeted CAR T cells. RESULTS: No significant difference was found between the donor-derived (n = 18) and patient-derived (n = 16) CAR T-cell subgroups in terms of efficacy. Complete remission/complete remission with incomplete count recovery rate (94.4% versus 75.0%, P = 0.1642), duration of response (median, 633.0 versus 373.0 days, P = 0.8562), overall survival (median, 67.12 months versus undefined, P = 0.061) and event-free survival (median, 17.0 versus 12.42 months, P = 0.773) were comparable. With regard to safety, the incidence (55.6% versus 62.5%, P = 0.7385) and severity (P = 0.1802) of cytokine release syndrome were similar, as were the serum levels of interleukin 6 (median, 30.8 versus 40.0 pg/mL, P = 0.8329) and ferritin (median, 3788.6 versus 1781.3 μg/L, P = 0.3552). The incidence of acute graft-versus-host disease was significantly higher in the donor-derived super and safe CAR T-cell subgroup (33.33% versus 0.00%, P = 0.0198). The peak level of CAR T-cell amplification (median, 114 169 versus 316 000 copies, P = 0.2204) and the day reaching the peak (median, 9.5 versus 9.5 days, P = 0.8143) were both similar. CONCLUSIONS: B-ALL patients who relapse after allo-HSCT may benefit from either donor- or patient-derived CAR T-cell therapy, but the risk of graft-versus-host disease may be higher for donor-derived products.