Low-Dose CAR-T Shows Efficacy in Pediatric Systemic Lupus Erythematosus

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Low dose, CD19-targeted chimeric antigen receptor (CAR) T-cells were well-tolerated and showed efficacy in pediatric patients with systemic lupus erythematosus (SLE).¹

Data from a phase 1/2 study (NCT06222853) evaluating MC-1-50 CAR T cells were presented at The American Society of Nephrology (ASN) Kidney Week 2024 in San Diego, California, held October 23-26, by Xue He, Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

“Recent advancements indicate that CAR T cell therapy shows promise for treating SLE, there remains a significant lack of data in pediatrics,” He and coinvestigators wrote in their abstract.1

He and colleagues manufactured MC-1-50 CAR T cells with the PRIMCAR manufacturing platform. Most participants received preconditioning with fludarabine (30 mg/m2) and cyclophosphamide (300 mg/m2) daily for 3 days. Investigators reduced dosages in some participants due to infections or intolerance.

As of August 2024, the investigators had infused 11 participants with MC-1-50. With doses ranging from 0.3×10^5/kg cells to 3×10^5/kg cells. Grade 1 cytokine release syndrome (CRS) occurred in 9 participants (81.8%) and grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 2 participants (18.2%). No unexpected adverse events (AE) or serious AEs were reported.¹

Five participants have follow-up for over 3 months and 4 have achieved Systemic Lupus Erythematosus Responder Index (SRI-4) responses. The fifth participant had persistent proteinuria at 3 months but achieved normalization in all other active indicators, with her serum creatinine levels declining from a peak of 786 to 169μmol/L and her urine output increasing from 50-100ml/day to 1000mL/day.¹

He and colleagues noted that the other participants have had varying degrees of improvement and CAR T-cell expansion was observed in all dose levels. B cells were rapidly eliminated within 7 days after infusion and reconstituted, mostly as naive B-cells, in most participants by the second month.

The research adds important data on the use of CAR T-cells in pediatric patients with SLE. One of the pioneers in the space of CAR T-cells for autoimmune disease, Kyverna Therapeutics, recently presented data on its investigational KYV-101 CAR T-cell therapy across indications including SLE, lupus nephritis (LN), myasthenia gravis, multiple sclerosis, and IgG4-related disease.²

The data were a mixed bag, with the patients with MG and the longest follow-up maintaining her durable immunomodulator-free response while another patient treated with LN experienced disease recurrence at 5 months posttreatment, despite having an initial disease response. KYV-101 continued to have a manageable safety profile, with 25 cases of CRS and 3 cases of ICANS, all below grade 3. The data need to mature in order to look closer into factors of durability in patients’ responses.²

"CAR T-cell therapies are rapidly establishing themselves as the new North star in the autoimmune disease treatment universe," Peter Maag, PhD, the chief executive officer of Kyverna, said in a statement.² "We are seeing rising interests in unlocking the full potential of cell therapies in rheumatological and neurological B-cell driven autoimmune diseases."

REFERENCES
1. Liu Q, He X, Zhang Y, Liu F, Wang J, Mao J. Safety and Efficacy of Low-Dose CD19-Targeted CAR T Cells in Refractory Pediatric Systemic Lupus Erythematosus (SLE). Presented at: ASN Kidney Week 2024; San Diego, California; October 23-26. Abstract SA-OR100

2. Maag P. Anti-CD19 CAR T-cell therapy in rheumatologic autoimmune diseases and beyond. Presented at:EULAR European Congress of Rheumatology 2024, held June 12-15, in Vienna, Austria.