Immunoglobulin light chain amyloidosis: 2024 update on diagnosis, prognosis, and treatment

Abstract

Disease OverviewImmunoglobulin 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 MGUS.”DiagnosisTissue biopsy stained with Congo red demonstrating amyloid deposits with apple‐green birefringence is required for the diagnosis of AL amyloidosis. 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.PrognosisN‐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.TherapyAll 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, venetoclax, and bendamustine.Future ChallengesDelayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end‐stage organ failure. Trials of antibodies to deplete deposited fibrils are underway.

A Simple Frailty Score Predicts Survival and Early Mortality in Systemic AL Amyloidosis

“…The prognosis assessment in AL amyloidosis is a rapidly changing field. Stage is considered the most important predictor of outcome [39]. However, the use of two different staging systems has potential for stage to be confounder [40].…”

Recent Advances and Future Directions in Syncope Management: A Comprehensive Narrative Review

“…Primary causes of dysautonomia include pure atrophy, multisystem atrophy, Parkinson's disease, and Lewy body dementia [25]. Secondary dysautonomia is caused by diabetes [26], amyloidosis [27], uremia [28], metabolic syndrome [29], heart failure [30], or other cardiovascular and non-cardiovascular diseases [31,32], as well as drugs causing sympathetic inhibition (e.g., antipsychotics via α1 and d2, antidepressants via antimuscarinic activity), vasodilation, cardio-inhibitory effects, or volume depletion (diuretics) [33]. Both acute SARS-CoV-2 infection and its post-acute sequelae are characterized by autonomic dysfunction and an altered mechanism of blood pressure variability and may manifest as syncope [34,35].…”

Treatment patterns for AL amyloidosis after frontline daratumumab, bortezomib, cyclophosphamide, and dexamethasone treatment failures

“…The immediate goal for therapy in patients with systemic immunoglobulin light chain amyloidosis (AL) is to swiftly achieve at least a hematologic very good partial response (VGPR), given the consistently improved organ responses and survival with achievement of deep hematologic responses [ 1 – 3 ]. The phase III ANDROMEDA trial demonstrated that the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone (D-VCd) resulted in significantly higher hematologic CR (53%) and VGPR rates (78%) compared to VCd in previously untreated patients [ 4 ].…”