Relapsed/refractory (R/R) light chain cardiac amyloidosis is associated with a poor prognosis, and cellular immunotherapy constitutes a crucial therapeutic modality for these patients. The efficacy and safety of CAR-T therapy have been reported in relevant studies; however, CAR-T manufacturing requires a lengthy timeline, and the leukapheresis procedure places an additional cardiac burden on patients. CAR-NK therapy boasts superior safety profiles compared with CAR-T therapy, and natural killer (NK) cells feature a wide range of sources. Investigators have accumulated prior experience in the clinical application of CAR-NK therapy, and has also achieved the successful development and preclinical application of CD19/BCMA dual-target CAR-T products. Furthermore, in the institution of the Investigator, there are dozens of newly diagnosed and more than 100 follow-up patients with AL cardiac amyloidosis each year. Investigators propose to initiate a phase I/II prospective clinical study to assess the safety and efficacy of umbilical cord blood-derived BCMA/CD19-targeted CAR-NK cell therapy for participants with relapsed/refractory light chain cardiac amyloidosis.
Voluntarily participate in this study and sign the informed consent form.
Aged 18 to 75 years, of either sex.
Pathologically confirmed amyloidosis, with positive Congo red staining of tissue specimens, green birefringent material observed under polarizing microscope, or characteristic electron microscopic findings.
Echocardiography: Mean ventricular wall thickness > 12 mm with no other identifiable cardiac etiologies.
NT-ProBNP ≥ 8500 ng/L;
Heart failure of New York Heart Association (NYHA) functional class IIIB or IV ;
Heart failure judged by the investigator to be caused by ischemic heart disease (e.g., a previous myocardial infarction with documented elevated cardiac enzymes and electrocardiographic changes) or uncorrected valvular heart disease, rather than primarily by AL amyloidosis;
Hospitalization for unstable angina or myocardial infarction within 6 months prior to the first dose, or percutaneous coronary intervention with recent stent implantation within 6 months, or coronary artery bypass grafting within 6 months;
Single group
CAR-NK
Procedure/SurgeryR/R AL cardiac amyloidosis patients in the CD19/BCMA dual-target CAR-NK therapy arm
safty and efficacy
The overall incidence and severity of all adverse events were calculated using CTCAE Version 5.0. The incidence of treatment-emergent adverse events (TEAEs) and abnormal laboratory findings possibly or definitely related to CB CAR-NK-BCMA/CD19, as well as dose-limiting toxicities (DLTs), were assessed for any occurrence from the initiation of study treatment up to Day 28. Definition of Dose-Limiting Toxicity (DLT):Toxic events related to CB CAR-NK-BCMA/CD19 treatment occurring within 28 days post-infusion include: Grade ≥4 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS); Grade 3 CRS or ICANS with a duration of ≥7 days; Other Grade ≥3 hematological or non-hematological toxic reactions. The treatment efficacy in participants is evaluated in accordance with the LYRIC Efficacy Evaluation Criteria (2016).
the safety and efficacy of umbilical cord blood-derived CAR-NK cells targeting BCMA/CD19 (CB CAR-NK-BCMA/CD19) in the treatment of patients with light chain cardiac amyloidosis
General condition of participants, ECOG performance status, symptoms and physical signs, complete blood count (CBC), serum biochemistry, ferritin, coagulation function, immunofixation electrophoresis (IFE), free light chains (FLC), cardiac biomarker tests (high-sensitivity troponin, BNP or NT-proBNP), electrocardiogram (ECG), echocardiography, immune function tests, etc.; peripheral blood collection for detection of B-cell, cytokine and CAR expansion; efficacy assessments on Days 14 and 28 including IFE, κ/λ free light chains (κ/λ FLC), and cardiac biomarker tests (high-sensitivity troponin, BNP or NT-proBNP).peripheral blood collection for detection of T-cell, cytokine and CAR expansion; assessment of comorbidities.
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