Low-dose, CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has shown efficacy and is well-tolerated in pediatric patients suffering from systemic lupus erythematosus (SLE). The findings from a phase 1/2 study evaluating MC-1-50 CAR T cells were shared at The American Society of Nephrology (ASN) Kidney Week 2024 in San Diego, California, from October 23 to 26, by Xue He from the Children’s Hospital of Zhejiang University School of Medicine.
The research team highlighted that while recent advancements suggest CAR T-cell therapy could be beneficial for treating SLE, there is still a critical lack of data specific to pediatric patients. They used the PRIMCAR manufacturing platform to develop the MC-1-50 CAR T cells, with most study participants undergoing preconditioning with fludarabine and cyclophosphamide for three days. In some cases, dosages were adjusted due to infections or intolerance.
As of August 2024, the study had infused 11 participants with MC-1-50, using doses from 0.3×10^5/kg to 3×10^5/kg. The majority experienced grade 1 cytokine release syndrome (81.8%) and grade 1 immune effector cell-associated neurotoxicity syndrome (18.2%). Notably, there were no unexpected adverse events reported.
Among the participants, five have been followed for over three months, with four achieving positive Systemic Lupus Erythematosus Responder Index responses. One participant demonstrated significant improvements in overall health indicators, including a decline in serum creatinine levels and increased urine output.
The researchers noted that CAR T-cell expansion occurred across all dose levels, and B cells were notably eliminated shortly after infusion, reconstituting mainly as naive B cells in the subsequent months. This study contributes valuable data regarding the use of CAR T-cell therapy in pediatric SLE patients.
Additionally, Kyverna Therapeutics, a pioneer in CAR T-cell therapy for autoimmune diseases, presented findings on their investigational KYV-101 across various indications, including SLE, lupus nephritis, and others. The outcomes varied, with some patients experiencing durable responses while others faced disease recurrence. The safety profile remains manageable, and further maturation of the data is needed to fully understand the durability of these responses.
Peter Maag, CEO of Kyverna, commented on the burgeoning interest in harnessing cell therapies for autoimmune diseases, emphasizing their potential as a significant advancement in treatment approaches.