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

Prior treatment

• Major surgery within 30 days before enrollment.

Other illness

• Active hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, or other acquired or congenital immunodeficiency disorders.
• 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.

Other

• Baseline peripheral neuropathy or neuropathic pain of grade ≥ 2 according to NCI CTCAE v4.0.

• Age ≥ 18 years.
• Confirmed systemic light-chain amyloidosis, meeting both of the following:
  • 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.
  • 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:
  • Mean ventricular wall thickness \> 12 mm on echocardiography, with other cardiac diseases excluded; or
  • 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:
  • Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis and immunofixation performed by the central laboratory;
  • Serum free light chain ≥ 50 mg/L with an abnormal kappa/lambda ratio; or
  • 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.