Immunoglobulin light chain amyloidosis: 2022 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 of undetermined significance (MGUS)."

DIAGNOSIS: Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. 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 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 groups of similar size; median survivals are 73, 35, 15, and 5 months.

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 complete response (CR). In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine.

FUTURE CHALLENGES: Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to catabolize deposited fibrils are underway.