免疫球蛋白轻链淀粉样变性：诊断、预后和治疗 2026 年更新

DISEASE OVERVIEW: AL amyloidosis is a clonal plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include HFpEF, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or MGUS." DIAGNOSIS: Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. PROGNOSIS: N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T (or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5 year survivals are 82%, 62%, 34%, and 20% respectively.

THERAPY: All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a VGPR. In patients failing to achieve this depth of response, options for consolidation include pomalidomide, stem cell transplantation, and venetoclax.

T-cell redirecting therapies, both bispecific antibodies and car T, show high level activity and may soon become standard second-line therapy. FUTURE CHALLENGES: Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. An antibody to deplete deposited fibrils has reported benefit in patients with cardiomyopathy.