Blinatumomab in Refractory Active Childhood Systemic Lupus Erythematosus

Inclusion Criteria:

Participants must meet all the following criteria to be eligible for enrollment:

1. Age: ≥ 5 years old.

2. Diagnosis: Diagnosed with systemic lupus erythematosus (SLE) based on the 2019EULAR/ACR classification criteria.

3. Positive Antibody: At least one of the following antibodies positive within 12months before screening or during the screening period:

• Antinuclear antibody (ANA) ≥ 1:80.

• Anti-double-stranded DNA (anti-dsDNA) antibody above the upper limit of normal (ULN).

• Anti-Smith (Anti-Sm) antibody above the ULN.

4. Treatment Resistance: Inadequate response to at least three of the following:

• Oral corticosteroids (OCS),

• Antimalarials,

• Conventional immunosuppressants (e.g., cyclophosphamide, mycophenolate mofetil,azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide),

• Biologics (e.g., TULIP-2, belimumab, rituximab). At least one treatment mustinvolve immunosuppressants or biologics.

5. SLEDAI-2000 Score: ≥ 6 based on the SLEDAI-2000 scoring system.

6. Stable Standard Treatment: Currently receiving one or more of the followingtreatments at a stable dose:

• OCS: ≤ 20 mg/day of prednisone or equivalent, with the dose stable for at least 7 days prior to the first dose of study medication.

• Antimalarials: Dose stable for at least 7 days prior to the first dose.

• Conventional immunosuppressants: Stable dose for at least 6 weeks beforescreening and throughout the study.

7. Laboratory Parameters:

• Absolute lymphocyte count (ALC) ≥ 0.5 × 10⁹/L.

• Peripheral CD19+ B cell count ≥ 25 cells/μL.

• Absolute neutrophil count (ANC) ≥ 0.5 × 10⁹/L.

• Hemoglobin ≥ 80 g/L.

• Platelet count ≥ 75 × 10⁹/L.

• Left ventricular ejection fraction (LVEF) ≥ 55% with no significant ECGabnormalities.

• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m².

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN;total bilirubin ≤ 2 × ULN.

• No severe pulmonary lesions, SpO₂ ≥ 92%.

8. Contraception: Female participants of childbearing potential must have a negativeurine pregnancy test and agree to use effective contraception during the study andfor 1 year after infusion.

9. Informed Consent: The participant and their legal guardian must provide writteninformed consent, demonstrating understanding of the study objectives andwillingness.

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded:

1. Central nervous system disease: active or unstable lupus-related neuropsychiatricdisease within 60 days, including epilepsy, confusion, cerebrovascular events, etc.;

2. Acute severe nephritis: renal replacement therapy within 3 months before thescreening period or ongoing, or significant kidney disease that, in the opinion ofthe investigator, may occur and lead to the need for high-dose glucocorticoid (prednisone dose ≥ 1 mg/kg/d or equivalent of other hormones), cyclophosphamide orMMF treatment within the first 3 months of the study;

3. Severe antiphospholipid syndrome within 12 months before or during screening；

4. Congenital heart disease or a history of acute myocardial infarction within 6 monthsbefore screening, or severe arrhythmia (including polymorphic ventriculartachycardia, ventricular tachycardia, etc.); or combined with moderate to largepericardial effusion, severe myocarditis, etc.; or unstable vital signs, patientswho need blood pressure-raising drugs to maintain blood pressure;

5. Suffering from other diseases that require long-term administration ofglucocorticoids or immunosuppressive agents;

6. Having active infections or uncontrollable infections that require systemictreatment within one week before screening;

7. Having received solid organ transplantation or hematopoietic stem celltransplantation within three months before screening; or having grade 2 or higheracute graft-versus-host disease (GVHD) within two weeks before screening;

8. History of severe recurrent or chronic infections, especially recurrent or chronicinfections associated with respiratory problems.

9. Immunoglobulin G levels below the lower limit (5-8 years: <4.5 g/L, 9 years andolder: <6.0 g/L);

10. History of hepatitis B virus (HBV) infection or positive serology indicating currentor past HBV infection. Human immunodeficiency virus (HIV; positive HIV antibodytest) and active hepatitis C virus (HCV) infection (detectable HCV ribonucleic acid [RNA]). Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection;

11. A history of tuberculosis or active tuberculosis; or latent tuberculosis treatedbefore the baseline; or subjects with an indeterminate test result who screenedpositive for PPD or T-spot can be retested, but if the repeat test is alsoindeterminate, they are excluded;

12. Had a history of macrophage activation syndrome within 1 month prior to screening;

13. Had received any anti-CD19 or anti-CD20 therapy, such as rituximab, obinutuzumab,ocrelizumab, or ofatumumab, within 3 months prior to screening or during screening;

14. Received a JAK inhibitor, Bruton tyrosine kinase (BTK) inhibitor, or tyrosine kinase 2 (TYK2) inhibitor, baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib,or zanubrutinib within 30 days before screening or during screening. Tofacitinib),Upadacitinib, Filgotinib, Ibrutinib, Zanubrutinib, and Fenebrutinib, or anyinvestigational drug;

15. Treatment with cyclophosphamide or a biologic agent within 4 weeks prior toenrollment, including but not limited to adalimumab, etanercept, golimumab,infliximab, Infliximab), Belimumab, Ustekinumab, Anifrolumab, Secukinumab, orAtacicept;

16. Intolerance or contraindication to the investigational therapy, including a historyof severe allergies or allergic reactions to monoclonal antibodies, or a knownhypersensitivity to any of the ingredients in belimumab injection;

17. Live vaccine within 4 weeks prior to screening;

18. Positive blood pregnancy test;

19. Patients with known malignant diseases such as tumors before screening;

20. Patients who have participated in other clinical trials within 3 months prior toenrollment;

21. Patients with depression or suicidal tendencies;

22. Other situations where the investigator believes the patient is not suitable forparticipation in the study.