Tandem CD19/CD22 chimeric antigen receptor T-cell therapy (CAR T-cell therapy) uses a single construct engineered to recognise both CD19 and CD22 on malignant B cells. This dual-targeting approach is designed to address relapse driven by antigen loss after CD19-only CAR T by allowing tumour elimination even if one of the target antigens is absent.

The study, led by Antonio Pérez-Martínez, MD, PhD, head of the Pediatric Hemato-Oncology Department and the Advanced Cell Therapy Unit, La Paz University Hospital, Madrid, Spain, and colleagues, was published in The Lancet eBioMedicine.

Initial findings in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia showed eight complete remissions out of 10 patients by day 28, with seven achieving minimal residual disease negativity.

At 18 months, the overall survival was approximately 70%, indicating a potentially durable benefit in this high-risk group.

Although longer-term multicentre data are needed, the initial results suggest that tandem CD19/CD22 CAR T may provide deeper and more durable remissions. Tandem or dual CAR T cells reinfuse genetically modified T lymphocytes that recognise both CD19 and CD22. Targeting two antigens is intended to prevent tumour escape through downregulation or loss of a single antigen and may lower the risk for relapse compared with single-target CAR T approaches.

In an interview with El Médico Interactivo, part of the Medscape Professional Network, Pérez-Martínez said, “The study enrolled children and adolescents younger than 18 years with CD22-positive and/or CD19-positive B-cell lymphoblastic leukaemia that was relapsed or refractory after all available lines of therapy, including tisagenlecleucel and/or transplant, and who were clinically stable to receive CAR T.”

After two patients with CD19-negative disease did not respond, eligibility was limited to those with CD19-positive and CD22-positive blasts.

The treatment strategy combines tandem CD19/CD22 CAR T with consolidative haematopoietic stem cell transplant. Pérez-Martínez noted that “patients require close clinical, immunological, and haematological monitoring to detect relapse, late toxicity, and posttransplant complications.”

The most frequent acute toxicities were cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, both of which are generally reversible.

The long-term effects were less severe than those seen with intensive chemotherapy and were mainly related to previous treatments.

In the long term, complications appear to be less severe than those seen with intensive chemotherapy and are mainly related to prior treatments.

Pérez-Martínez noted that “persistent hypogammaglobulinaemia, risk for infection, and mild neurocognitive impairment in some cases have been observed.”

“We are developing CAR T-cell constructs targeting CD7, CD45, and CD30, with potential applications in acute T-cell leukaemias, juvenile myelomonocytic leukaemia, acute myeloid leukaemia, and Hodgkin lymphoma,” Pérez-Martínez said.

This story was translated from El Medico Interactivo.