New treatment approach for idiopathic multicentric Castleman disease using an anti-IL-6 receptor antibody

Inclusion Criteria:

* Age ≥18 years, regardless of gender;
* Biopsy or central pathological examination confirmed measurable, symptomatic iMCD (diagnosed according to the guideline for the diagnosis and treatment of Castleman disease in China (2025 )), with the patient presenting at least one of the following symptoms: fatigue, anorexia, fever, or weight loss;
* Clinical laboratory values within 4 weeks prior to the first dose meeting the following criteria:

  * Absolute neutrophil count (ANC) ≥1.0×10⁹/L;
  * Platelet count (PLT) ≥75×10⁹/L;
  * Alanine aminotransferase (ALT) \<2.5×ULN;
  * Total bilirubin (TBIL) \<2.5×ULN;
  * Serum creatinine (SCr) ≤3.0 mg/dL (265 μmol/L).
* ECOG-PS performance status score of 0, 1, or 2;
* If corticosteroids are used (e.g., prednisone), the dose should not exceed 1 mg/kg/day (or equivalent dose of other corticosteroids, see appendix), and must have been stable or reduced within 4 weeks prior to the first dose;
* Patients of childbearing potential (male and female) must agree to use effective contraception during the trial and for 6 months after the last dose; males must not donate sperm and females must not donate oocyte during this period;
* The patient (or their legal guardian or impartial witness) must sign the informed consent form before any study-specific procedures are performed, indicating understanding of the study purpose and required procedures, and voluntary participation in the study.

Exclusion Criteria:

* Individuals positive for HIV or HHV-8;
* Those with skin lesions as the only measurable lesion;
* Patients with concurrent malignancies within 5 years prior to screening, except for the following: adequately treated basal cell carcinoma or squamous cell carcinoma, carcinoma in situ of the cervix;
* Patients with concurrent diseases that may interfere with the study process or results, such as autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, adult-onset Still's disease, juvenile idiopathic arthritis, autoimmune lymphoproliferative syndrome), active systemic infection, poorly controlled diabetes, acute diffuse lung disease, active tuberculosis;
* History of uncontrolled cardiac disease, such as unstable angina, congestive heart failure, myocardial infarction within the past 12 months, hemodynamic instability, known left ventricular ejection fraction (LVEF) \<40%, or clinically significant rhythm or conduction abnormalities;
* Patients with any of the following positive test results: HBsAg-positive with HBV-DNA titer \>1000 IU/mL, hepatitis C virus antibody (HCV-Ab), Treponema pallidum antibody (TP-Ab);
* History of allogeneic transplantation (except corneal transplantation);
* History of paraneoplastic pemphigus or bronchiolitis obliterans;
* Patients with a history of bleeding:

  * Intracranial hemorrhage within 6 months prior to screening;
  * Active bleeding within 2 months prior to screening.
* History of cerebral infarction within 6 months prior to screening (except lacunar infarction);
* Patients who have received prohibited treatments or plan to use the following treatments during the study:

  * Prior treatment with IL-6/IL-6R targeted therapy before the first dose;
  * Other concomitant anti-tumor therapies for Castleman disease (e.g., anti-CD20 antibodies, chemotherapy) within 8 weeks prior to the first dose;
  * Biologics such as anti-tumor necrosis factor-α (TNF-α) antibodies within 8 weeks prior to the first dose;
  * Erythropoiesis-stimulating agents (ESAs) within 8 weeks prior to the first dose;
  * Immunosuppressants (except stable doses of corticosteroids) within 4 weeks prior to the first dose;
  * Any systemic therapy for Castleman disease within 4 weeks prior to the first dose;
  * Major surgery or radiotherapy within 4 weeks prior to the first dose;
  * Current use or planned use of strong CYP3A inhibitors/inducers during the study；
* Known history of severe infusion reactions to monoclonal antibodies or human albumin;
* Severe psychiatric disorders that may compromise compliance with treatment;
* Vaccination with live or attenuated live vaccines within 4 weeks prior to the first dose or planned vaccination during the trial;
* Pregnant or lactating females, or those planning pregnancy within 6 months after the last dose;
* Participation in other clinical trials within 1 month prior to the first dose;
* Any other condition deemed by the investigator as unsuitable for participation in this trial.