Recent advances in understanding and treating immunoglobulin light chain amyloidosis

Abstract

Immunoglobulin (Ig) light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by misfolded Ig light chain deposition in vital organs of the body, resulting in proteotoxicity and organ dysfunction. Owing to its diverse clinical presentations and a tendency to mimic common medical conditions, AL amyloidosis is often diagnosed late and results in dismal outcomes. Early referral to a specialized center with expertise in management of AL amyloidosis is always recommended. The availability of sensitive biomarkers and novel therapies is reforming our approach to how we manage AL amyloidosis. Treatment for patients with AL amyloidosis should be risk-adapted and customized on the basis of individual patient characteristics. In the future, approaches directed at amyloid fibril clearance in combination with agents that target plasma cells will be needed both to eradicate the malignant clone and to establish organ responses.

Patient outcomes in light chain (AL) amyloidosis: The clock is ticking from symptoms to diagnosis

“…Although it is possible that the inexact nature of this calculation may have resulted in misclassification of some subjects, the impact of any imprecise assignments is expected to be minor as this method for time calculation was used consistently. Other considerations regarding the generalizability of our results include the ever‐changing landscape of available treatments for AL amyloidosis, as well as the recent evidence suggesting the important impact of cytogenetics on prognosis and response to specific treatments 17,26,27 . The emergence of new investigational therapies over the past several years has assisted in improving both prognosis and survival in this patient population 28‐30 .…”

“…The most commonly used available treatments include chemotherapy (which can include single or combination alkylating agents, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies) and autologous stem cell transplantation 1,14,16 . While these strategies represent tremendous advances in the treatment of patients with AL amyloidosis, 6‐month mortality has largely remained unchanged over the past two decades 9,16‐18 …”

From Clinical Clues to Final Diagnosis: The Return of Detective Work to Clinical Medicine in Cardiac Amyloidosis

“…The first priority is to rule out AL amyloidosis, since it is considered a life-threatening hematological emergency ( 3 , 27 ). Patients with AL amyloidosis have poor survival (<6 months) if untreated, but there are a number of chemotherapeutic and disease-modifying therapies available for the management of this condition ( 28 , 29 ).…”

Contrasting presentations of the same disease: A comparison of two cases of amyloidosis presenting with eyelid involvement

“…Transthyretin amyloidosis and familial amyloidosis are two types of systemic amyloidosis that more frequently involve the eye. 3 In contrast, localized amyloidosis is most frequently characterized by local deposition of immunoglobulin light chains (usually kappa or lambda) and is referred to as localized light chain amyloidosis. 4 Localized amyloidosis can affect numerous tissues throughout the body, including the eyelid/peri-ocular structures, cardiac atrea, larynx, ureter, and skin.…”