CAR-NK Therapy for Cardiac Amyloidosis

Inclusion Criteria

• •1. Voluntarily participate in this study and sign the informed consent form.
• •2. Aged 18 to 75 years, of either sex.
• •3. Pathologically confirmed amyloidosis, with positive Congo red staining of tissue specimens, green birefringent material observed under polarizing microscope, or characteristic electron microscopic findings.
• •4. Presence of measurable light chain amyloidosis lesions meeting at least one of the following criteria:
• •1）Serum M-protein ≥ 0.5 g/dL (detected by routine serum protein electrophoresis and immunofixation electrophoresis).
• •2）Abnormal κ/λ ratio, with the difference between involved and uninvolved free light chains (dFLC) ≥ 50 mg/L.
• •5\. Confirmed cardiac involvement by amyloidosis, meeting at least one of the following criteria; extramyocardial organ involvement is permitted:
• •1. Echocardiography: Mean ventricular wall thickness \> 12 mm with no other identifiable cardiac etiologies.
• •2. Elevated NT-ProBNP level (\> 332 ng/L) without concomitant renal failure or atrial fibrillation.
• •6\. Having received at least one course of first-line therapy based on bortezomib or CD38 monoclonal antibody with suboptimal hematological response, meeting at least one of the following criteria:
• •1. Failure to achieve partial response (PR) after 1 treatment cycle.
• •2. Failure to achieve very good partial response (VGPR) after 2 treatment cycles. 7. Estimated overall survival ≥ 12 weeks. 8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 3.
• •9\. Sufficient organ function reserve excluding the heart, meeting all the following criteria:
• •1. Peripheral blood neutrophil count ≥ 1000/μL, hemoglobin ≥ 7 g/dL, platelet count ≥ 50,000/μL; red blood cell or platelet transfusion is permitted within 1 week prior to screening.
• •2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper normal limit (UNL).
• •3. Serum total bilirubin ≤ 1.5 × UNL.
• •4. Estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m², calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
• •5. Baseline oxygen saturation \> 92% in a natural indoor air environment. 10. A prior history of one hematopoietic stem cell transplantation is permitted.
• •11\. At least 3 weeks have elapsed since the completion of approved therapeutic interventions for AL cardiac amyloidosis (e.g., systemic chemotherapy, immunotherapy) prior to the administration of the study drug.
• •12\. Female subjects of childbearing potential must have a negative pregnancy test and agree to adopt effective contraceptive measures during the trial period.