Rapid normalization of platelet counts in patients with refractory thrombocytopenia associated with systemic lupus erythematosus (SLE) following treatment with allogeneic dual-target CD19/BCMA CAR T-cell therapy (QT-019B)

Abstract Background Systemic lupus erythematosus with immune thrombocytopenia (SLE-ITP) is a severe condition associated with poor prognosis and increased mortality. A significant proportion of patients fail to respond or relapse after standard therapies, underscoring the need for novel treatments. Previous reports have shown that autologous aCD19 CAR T-cell therapy can induce deep remission in refractory SLE, including a case of SLE-ITP that responded with profound B-cell depletion (Li, et al. N Engl J Med 2024). However, autologous CAR-T cells have limitations for widespread use because of their high cost and complex manufacturing processes. To overcome these challenges, we developed an allogeneic CAR-T product targeting both CD19 and BCMA, QT-019B, designed to achieve immune reset by thoroughly eliminating autoantibody-producing cells. Methods In this investigator-initiated trial (NCT06941129), we used QT-019B to eliminate autoantibody-producing cells at all stages. Using a “3+3” dose escalation approach, six patients with refractory SLE-ITP received a single infusion of QT-019B after lymphodepleting conditioning with fludarabine and cyclophosphamide. Results Four patients have completed the dose-limiting toxicity (DLT) observation period (three at a dose of 1e6.kg and one at 3e6.kg), while two patients are still undergoing DLT observation at a dose of 3e6.kg. Among the first four patients who completed the DLT observation with follow-up periods of 5, 4, 3, and 3 months, we noted robust in vivo expansion of the CAR T-cells in all patients, accompanied by complete elimination of pathogenic autoantibodies. Three out of four patients achieved a prompt and durable complete response (CR), with platelet counts restoring to normal levels within one month and maintaining that normalization. Patient 1 reached a Cmax of 58,957 copies/µg DNA on Day 14 and was the only non-responder. She had pre-existing aplastic anemia, as shown by her bone marrow smear and biopsy, which likely explains the lack of rapid platelet recovery despite effective depletion of B-cells and plasma cells. Notably, at the latest follow-up in early July 2025 (Month 4), this patient demonstrated improvement in her bone marrow, resulting in a stable and increasing platelet count. Patient 2 reached a Cmax of 10,645 copies/µg DNA on Day 10. Her baseline platelet count was 33×10^9/L, defined as the most recent test result prior to lymphodepletion. From Day 12 onward, her platelet count increased rapidly and remained stable through the latest follow-up. Notably, all autoantibodies that were positive at baseline (ANA, dsDNA, SSA60, and GPIIb/IIIa) became negative by Day 28 and have stayed negative. Patient 3 reached a Cmax of 19,396 copies/µg DNA on Day 11. Her platelet count, which was initially low at 7×10^9/L, quickly returned to normal starting from Day 10 and remained stable through the most recent follow-up. Importantly, all autoantibodies that were positive at baseline (ANA and GPIIb/IIIa) turned negative by Day 28 and have remained negative. Patient 4 reached a Cmax of 45,673 copies/µg DNA on Day 11. Her baseline platelet count was 33×10^9/L. Beginning on Day 11, her platelet count rose rapidly and stayed stable through the latest follow-up. All autoantibodies that were positive at baseline (ANA and GPIb/IX) became negative by Day 28 and have remained negative. Furthermore, all patients who responded were able to discontinue most glucocorticoids and other immunosuppressive medications following CAR T-cell therapy. The treatment was generally well tolerated: only Patient 1 had mild (grade 1) cytokine release syndrome, and no other major CAR T-related side effects or serious infections have been reported to date. At the ASH meeting, we will present combined data from all six patients, including evidence of immune reset, such as flow cytometry. Additionally, we will provide single-cell RNA sequencing data from both bone marrow and peripheral blood samples of at least one patient. Conclusions In conclusion, the allogeneic dual-target anti-CD19/BCMA CAR T-cell therapy (QT-019B) demonstrated encouraging pharmacokinetics, pharmacodynamics, safety, and efficacy in this limited group of patients with refractory SLE-ITP. QT-019B led to high CR rates and enabled patients to become medication-free, offering a compelling reason to advance QT-019B in investigational new drug application (IND) trials and to investigate QT-019B for other difficult-to-treat autoimmune disorders.