Selinexor, Daratumumab, and Dexamethasone (XDd) for Light-Chain Cardiac Amyloidosis

The goal of this clinical trial is to evaluate whether selinexor combined with daratumumab and dexamethasone (XDd) can treat patients with advanced light-chain cardiac amyloidosis. The main questions it aims to answer are: Does XDd regimen achieve hematologic complete response in patients with advanced light-chain cardiac amyloidosis? Does XDd regimen improve cardiac response, organ response, progression-free survival, overall survival, quality of life, and safety?

Inclusion Criteria: * Age ≥ 18 years. * Confirmed systemic light-chain amyloidosis, meeting both of the following: 1. Tissue biopsy confirms amyloid deposition, and the amyloid precursor protein is immunoglobulin light chain or heavy-light chain. Pathologic evidence includes at least one of the following: Congo red staining positive with apple-green birefringence under polarized light microscopy; Light-chain restricted expression demonstrated by immunohistochemistry, immunofluorescence, or immunoelectron microscopy, or mass spectrometry confirming the precursor protein as immunoglobulin light chain; Electron microscopy showing nonbranching, rigid, randomly arranged fibrils with a diameter of 8 to 14 nm. 2. Evidence of monoclonal immunoglobulin or free light chain in serum or urine, or detection of monoclonal plasma cells/B cells in bone marrow examination. * Clinical manifestations, physical examination, laboratory tests, or imaging studies confirm involvement of one or more organs, with mandatory cardiac involvement. Cardiac involvement is defined as either: 1. Mean ventricular wall thickness \> 12 mm on echocardiography, with other cardiac diseases excluded; or 2. NT-proBNP \> 332 ng/L in the absence of renal insufficiency and atrial fibrillation. * Mayo 2004 stage IIIa or IIIb disease, including newly diagnosed and relapsed/refractory patients. * Measurable disease in light-chain amyloidosis, defined by at least one of the following: 1. Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis and immunofixation performed by the central laboratory; 2. Serum free light chain ≥ 50 mg/L with an abnormal kappa/lambda ratio; or 3. Difference between involved and uninvolved free light chains (dFLC) ≥ 50 mg/L. Note: Urine Bence Jones proteinuria alone is not sufficient to define measurable disease for eligibility. * Not pregnant or breastfeeding. Men and women of childbearing potential must agree to use appropriate contraception before treatment, during treatment, during any treatment interruption, and for 4 weeks after treatment completion. * Written informed consent has been signed by the participant. If the participant is unable to sign because of their medical condition, informed consent may be signed by a legal guardian or immediate family member. Exclusion Criteria: * Active hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, or other acquired or congenital immunodeficiency disorders. * Baseline peripheral neuropathy or neuropathic pain of grade ≥ 2 according to NCI CTCAE v4.0. * Major surgery within 30 days before enrollment. * Epilepsy requiring medication, dementia, or other psychiatric conditions that prevent understanding of or compliance with the study protocol. * Any severe physical or psychiatric illness that may interfere with participation in this clinical study. * Any other condition that the investigator considers unsuitable for enrollment.