Donor-derived CAR-T therapy improves the survival of relapsed B-ALL after allogeneic transplantation compared with donor lymphocyte infusion

Hum Cell. 2023 Sep;36(5):1716-1728. doi: 10.1007/s13577-023-00934-2. Epub 2023 Jul 7.

Abstract

Chimeric antigen receptor (CAR)-T cell therapy revolutionized treatment for various hematologic malignances. However, limited studies were reported to compare the efficacy and safety of CAR-T and donor lymphocyte infusion (DLI) for patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) after hematopoietic stem cell transplantation (HSCT) comprehensively. We conducted a single-center, retrospective comparative study that consisted of 12 patients who were treated with DLI (control group) and 12 patients treated with donor-derived CD19 CAR-T cells (experimental group, 6 patients also received CD22 or CD123 CAR-T cells sequentially) with 3 overlaps. The event-free survival (EFS) of patients in experimental group was superior to that of the control group: 516 days versus 98 days (p = 0.0415). Compared with 7 of 12 patients treated with DLI suffered grades III-IV acute graft versus host disease (aGVHD), one grade III aGVHD developed in patients treated with CAR-T therapy. No significant difference in the incidence of infection was identified between these two groups. Most patients in the experimental group had only mild cytokine release syndrome and none developed neurotoxicity. The univariate analysis of patients in the experiment group revealed that earlier CAR-T therapy for post-transplantation relapse was associated with better EFS. There was no significant difference in EFS between patients treated with dual-target CAR-T with those with single CD19 CAR-T. In this study, our data supported that donor-derived CAR-T therapy is a safe and potentially effective treatment for relapsed B-ALL after HSCT and may be superior to DLI.

Keywords: Acute graft versus host disease rate; B-cell acute lymphoblastic leukemia; CAR-T cell therapy; Donor lymphocyte infusion; Immunology.

MeSH terms

  • Antigens, CD19
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / therapy
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Lymphocytes
  • Receptors, Chimeric Antigen*
  • Retrospective Studies
  • Transplantation, Homologous / adverse effects

Substances

  • Receptors, Chimeric Antigen
  • Antigens, CD19