International Journal Publication | Dr. Jing PAN and Prof. Xiaoming Feng's Teams Report Phase 1/2 Trial of Autologous CD19 CAR-T Therapy in Pediatric and Adult SLE

Summary: The team led by Dr. Jing PAN at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, together with Prof. Xiaoming Feng's team at Hangzhou Normal University, published the results of a phase 1/2 clinical trial of autologous CD19 CAR-T therapy in pediatric and adult systemic lupus erythematosus (SLE) in Molecular Therapy. The study enrolled 18 patients, including 15 children. At month 6, 14 patients achieved DORIS-defined remission; among the 15 pediatric patients, 11 achieved DORIS remission. Anti-dsDNA antibodies became negative in 88.9% of patients who were positive at baseline. The safety profile was generally favorable, with only mild cytokine release syndrome (CRS) and neurotoxicity reported and no grade 3 or higher infections. The findings provide important clinical evidence supporting the potential of CD19 CAR-T therapy to help some patients with SLE achieve sustained remission without long-term immunosuppressive medication.

For people living with systemic lupus erythematosus (SLE), long-term dependence on immunosuppressive therapy can bring cumulative toxicity, while disease flares may still recur. Achieving durable remission without continuous medication therefore remains an important unmet need in SLE care.

Recently, the team led by Dr. Jing PAN, who holds appointments at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, and Beijing GoBroad Hospital, collaborated with Prof. Xiaoming Feng's team at the School of Basic Medical Sciences, Hangzhou Normal University, to publish a study in Molecular Therapy titled "Autologous CD19 CAR-T cell therapy for pediatric and adult systemic lupus erythematosus: a phase 1/2 trial." The study reports detailed safety and efficacy data from a phase 1/2 clinical trial of autologous CD19 CAR-T therapy in pediatric and adult patients with SLE. The results suggest that CD19 CAR-T therapy can induce deep clinical remission in many patients after immunosuppressive drugs are discontinued, supporting further exploration of sustained medication-free remission.

SLE is a chronic autoimmune disease that can affect multiple organ systems. Its pathogenesis is driven in part by abnormally active autoreactive B cells, which continuously produce autoantibodies against nuclear antigens such as double-stranded DNA. This immune dysregulation can trigger systemic inflammation and progressive tissue damage involving organs such as the kidneys, liver, lungs, and skin. Pediatric SLE is often more severe than adult-onset disease. To maintain disease control, many patients require long-term or even lifelong glucocorticoids and other immunosuppressive therapies, which can increase the risk of infection and other complications; in children, prolonged treatment may also affect growth and development. Although B-cell-targeted monoclonal antibodies are available, durable medication-free remission remains difficult to achieve. In recent years, CAR-T therapy has shown strong clinical activity in hematologic malignancies and is increasingly being explored in autoimmune diseases. However, previous studies in SLE have generally involved small numbers of patients, creating a need for larger and more rigorous clinical trials to better define who may benefit and how durable the effect may be.

The study had two stages: dose escalation (phase 1) and dose expansion (phase 2). The main endpoints in phase 1 were the type and incidence of dose-limiting toxicities (DLTs) within 28 days after infusion, as well as the severity and incidence of adverse events (AEs) within 30 days. In phase 2, the primary endpoints were objective response rates at months 3 and 6, defined by the proportion of participants achieving an SRI-4 response. To identify an appropriate treatment dose while balancing safety and efficacy, the investigators used the TITE-BOIN12 trial design.

A total of 18 patients with SLE were enrolled. All had previously failed at least two immunosuppressive therapies, such as glucocorticoids, mycophenolate mofetil, or belimumab. The cohort included 15 children and 3 adults and represented a broad range of disease manifestations: 8 patients had lupus nephritis (LN), 2 had autoimmune hemolytic anemia (AIHA), and 1 had immune thrombocytopenia (ITP). To explore the value of earlier intervention, the study also included 3 patients with relatively low baseline disease activity (SLEDAI-2K score <4) but a high level of medication dependence. The starting dose in phase 1 was 1 x 10^6 CAR-T cells/kg. No dose-limiting toxicity was observed at this dose, and it received the highest overall benefit-risk score under the TITE-BOIN12 algorithm. It was therefore selected as the recommended phase 2 dose.

In this SLE study, treatment-related immune toxicity was generally mild. Thirteen patients developed grade 1 cytokine release syndrome (CRS), mainly presenting as fever. Three patients experienced mild grade 1 neurotoxicity (ICANS), including headache. No grade 3 or higher infections were reported. Fifteen patients developed grade 3 or higher cytopenias, but all subsequently recovered to grade 2 or lower.

Among the 15 evaluable patients with baseline SLEDAI-2K scores >=4, 12 achieved an SRI-4 response at month 6. Across all 18 patients, 14 achieved DORIS-defined remission at month 6, 2 reached lupus low disease activity state (LLDAS), and 2 did not respond. The cohort was predominantly pediatric: among the 15 children, 11 achieved DORIS remission, 2 reached LLDAS, and 2 did not respond at month 6. Among the 8 patients with lupus nephritis, 5 achieved DORIS remission, 1 reached LLDAS, and 2 did not respond. Some patients with class IV-V lupus nephritis who had not responded at month 3 showed improvement by month 6. Among 7 patients with proteinuria at baseline, 4 had proteinuria levels fall below 0.5 g/24 h by month 6. In all 4 patients with low complement levels at baseline, C3 and/or C4 returned to the normal range within 30 days. Of 9 patients who were positive for anti-dsDNA antibodies at baseline, 8 became negative, and 7 remained negative during follow-up. With a median follow-up of 10.2 months, 13 of the 14 patients who initially achieved DORIS remission, together with both patients who reached LLDAS, maintained remission or low disease activity without ongoing immunosuppressive therapy; one patient experienced disease relapse.

Overall, this phase 1/2 trial - which included patients with manifestations such as ITP, AIHA, and lupus nephritis - provides preliminary evidence that autologous CD19 CAR-T therapy can be both feasible and effective in SLE. The findings also suggest that cellular therapy before irreversible organ damage develops may help slow disease progression and reduce patients' long-term exposure to immunosuppressive treatment and its associated toxicity.