Immunoglobulin light chain amyloidosis: 2020 update on diagnosis, prognosis, and treatment

Disease Overview Immunoglobulin light chain amyloidosis is a clonal, nonproliferative 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 heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and atypical smoldering multiple myeloma or monoclonal gammopathy undetermined significance (MGUS). Diagnosis Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for diagnosis. Invasive organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy. Prognosis N-terminal pro-brain natriuretic peptide (NT-proBNP), serum troponin T, and difference between involved and uninvolved immunoglobulin free light chain (FLC) values are used to classify patients into four groups of similar size; median survivals are 94.1, 40.3, 14.0, and 5.8 months. Therapy All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Stem cell transplant (SCT) is preferred, but only 20% of patients are eligible. Requirements for safe SCT include systolic blood pressure >90 mmHg, troponin T < 0.06 ng/mL and serum creatinine <= 1.7 mg/dL. Nontransplant candidates can be offered cyclophosphamide-bortezomib-dexamethasone or daratumumab-containing regimens as it appears to be highly active in AL amyloidosis. Future Challenges Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure.