Autologous anti-CD19 CAR-T-cell therapy (TC BioPharm)

In the immunocompromised setting, recipients of solid-organ or hematopoietic stem-cell transplants carry an increased risk of post-transplant lymphoproliferative disorder (PTLD). Burkitt lymphoma (BL) PTLD is a rare form of monomorphic B-cell PTLD, which lacks a standard best treatment. Here, we report the successful treatment of refractory BL-PTLD with autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. A male patient was diagnosed with BL-PTLD, with an increasing Epstein-Barr virus (EBV) viral load, at 21 months after undergoing living liver transplantation from his mother due to neonatal biliary atresia. After 10 cycles rituximab +/− intensive chemotherapy and surgical tumor resection, the tumors significantly advanced. Next-generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded tumor tissue, revealing one mutation in exon 5, TP53: p.A159 V, which may be associated with chemo-resistance. Thus, treatment was started with autologous anti-CD19 CAR T-cell therapy. We administered 9.0 × 106/kg autologous anti-CD19 CAR T-cells, after conditioning with cyclophosphamide and fludarabine. Unexpectedly, the patient experienced only mild (Grade II) cytokine release syndrome (CRS) without neurotoxicity. Finally, he went into complete remission (CR), and has achieved 16-month event-free survival to date. In addition, liver function has remained stably within the normal range without any immunosuppressive therapy. The literature includes only five previously reported BL cases treated with CAR T-cell therapy. In conclusion, the present case suggests that autologous anti-CD19 CAR T-cell therapy may represent a new therapeutic option for some cases of refractory BL-PTLD. Clinical trial number: ChiCTR2000032211.

Pediatric Philadelphia chromosome-like (Ph-like) acute B-lymphoblastic leukemia (B-ALL), a high-risk subset of B-ALL characterized by a gene expression profile similar to that of Ph-positive ALL, has extremely poor outcome after a relapse following autologous chimeric antigen receptor (CAR)-T and haploidentical (haplo) hematopoietic stem cell transplantation(HSCT)therapy. with very limited treatment options. Donor-derived CAR T-cell therapy, the most vital advanced anticancer technology, may be a promising salvage strategy for patients with Ph-like B-ALL. Here, we presented a relapsed and refractory case of a child with Ph-like B-ALL after autologous anti-CD19 CAR T-cell therapy followed by haplo-HSCT. She successfully achieved the fourth complete remission (CR4) and maintained CR for five months after the sequential infusion of donor-derived anti-CD22 and anti-CD19 CAR T cells, with mild CRS side effects and no obvious graft-versus-host disease. A donor-derived anti-CD22 and -CD19 CAR T-cell therapy combined with a sequential infusion strategy may provide a promising alternative treatment strategy as effective and safe salvage therapy for children with recurrent and refractory Ph-like B-ALL after autologous CD19-directed CAR T-cell therapy followed by haplo-HSCT.