Immunoglobulin light chain amyloidosis: 2022 update on diagnosis, prognosis, and treatment

Abstract

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.

Real world data on light chain cardiac amyloidosis: Still a delayed diagnosis

“…However, a phase III, randomized, open-label, multicenter study showed no benefit from the addition of doxycycline in patients with cardiac involvement ( 25 ). It is well established that the extent of heart involvement in patients with amyloidosis is the major determinant of survival ( 26 ). In our analysis, the median OS from diagnosis to last follow-up or death was 14 months (range, 0.5-120 months).…”

Clinical characteristics and prognostic value of renal immune complex deposition in patients with light chain amyloidosis

“…Patients with systemic AL amyloidosis who were newly diagnosed by renal biopsy in Xijing Hospital (Xi’an, China) from December 2015 to March 2021 were included in our study. The diagnosis of systemic AL amyloidosis was confirmed by the presence of apple-green birefringence under polarized light after Congo red staining and the identification of fibrils with a diameter of 8–12 nm by electron microscopy ( 22 ). Patients who suffered from diabetes, membranous nephropathy, IgA nephropathy, or other confounding diseases based on relevant clinical and pathological information were excluded.…”

Localized light chain amyloidosis: A self-limited plasmacytic B-cell lymphoproliferative disorder

“…Thus, the diagnostic workup generally involves amyloid typing and ruling out a systemic B-cell lymphoproliferative disorder (most commonly systemic AL amyloidosis, multiple myeloma, and B-cell lymphoma). Therefore, testing should be performed to a) confirm immunoglobulin-derived amyloid fibrils with typing, ideally via liquid chromatography-tandem mass spectrometry (LC-MS/MS) ( 31 ), b) evaluate for evidence of a clonal plasma cell or B-cell population, c) rule out systemic organ involvement with AL amyloidosis, and d) characterize potential manifestations of localized organ involvement ( 32 – 34 ).…”