CD20 Monoclonal Antibody Combined With BTK Inhibitor for the Treatment of Refractory Immune-related Cytopenia

Clinical Study on the Treatment of Refractory Immune-related Cytopenia With CD20 Monoclonal Antibody Combined With BTK Inhibitor (BTKi)

This study aims to utilize anti-CD20 monoclonal antibodies to eliminate peripheral B cells and reduce the mechanism of autoantibody production, as well as combine the mechanism of BTK inhibitors (BTKi) blocking the B cell receptor signaling pathway and inhibiting B cell activation and proliferation, for the treatment of refractory immune-related cytopenia. In this study, it includes the salvage treatment of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA), expecting to achieve a synergistic and enhancing effect. This study aims to select Zuberitamab, a human-mouse chimeric anti-CD20 monoclonal antibody, and the BTKi Orelabrutinib as combination therapy options. The clinical efficacy of the Zuberitamab-Orelabrutinib combination therapy (overall response rate, duration of sustained remission) will be evaluated, along with its safety profile (including infections, bleeding, cardiac toxicity), to provide a theoretical basis for their combined use in treating refractory immune-related thrombocytopenia (ITP and AIHA).

Inclusion Criteria:

• Diagnosed with refractory immune-related cytopenia, including immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA);

• Age ranging from 18 to 80 years old (inclusive of 18 and 80);

• Expected survival time > 12 months;

• Good function of major organs:

  1. liver function: ALT/AST < 3 times the upper limit of normal;
  2. kidney function: creatinine < 100 μmol/L;
  3. lung function: indoor oxygen saturation ≥ 95%;
  4. heart function: left ventricular ejection fraction (LVEF) ≥ 50%;

• Peripheral superficial venous blood flow is unobstructed, capable of meeting the requirements for intravenous infusion;

• Karnofsky score ≥ 60, ECOG ≤ 2 points.

Exclusion Criteria:

• Women who are pregnant (with positive urine/blood pregnancy test results) or breastfeeding;

• Those who have severe underlying heart diseases when participating in this study, including:

  1. clinically significant atrial fibrillation (AF),
  2. cardiac conduction block,
  3. myocardial infarction (within 1 year),
  4. congestive heart failure (CHF);
  5. cardiac echocardiography LVEF < 50%;
  6. New York Heart Association (NYHA) cardiac function classification of III-IV grade;

• Those with active bleeding or bleeding tendencies, and those who need to take anticoagulant drugs;

• Those with organ dysfunction or uncontrollable coexisting diseases;

• History of malignant tumors;

• Those with active chronic hepatitis B or active hepatitis C;

• Known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome;

• Those with uncontrollable infectious diseases;

• As determined by the investigator, other unsuitable conditions exist.