The November 23, 2021, session of Duke Medicine LEADS featured Cristiana Costa Chase, DO, presenting "Amyloidosis Updates."
- AL amyloidosis is a heterogeneous and life-threatening disease caused by misfolded free light chains. It can cause significant impairment of one or many organ systems, with the most common being cardiac and renal. Common clinical presentations include restrictive cardiomyopathy (mean wall thickness >12 mm, NT-proBNP >332), glomerular dysfunction and albuminuria (24-h urine protein >0.5 g/d), hepatomegaly (>15cm) +/- elevated ALP, gut malabsorption, peripheral and autonomic neuropathies, bilateral carpal tunnel, macroglossia or tongue scalloping, etc.
- Work-up should entail biopsy of an affected organ with positive amyloid staining with Congo red, identification of the type of amyloid fibrils, assessment of monoclonal disease, and determination of the extent of systemic damage.
- Disease prognostication involves both plasma cellular factors (e.g., serum free light chain or FLC) and organ biomarkers (e.g., troponin-T > 0.035 or NT-proBNP >1800 pg/ml in cardiac amyloidosis). Despite an evolution in the treatment of AL amyloidosis, disease mortality remains high.
- The goal of treatment is both hematologic response (i.e. normalization of serum FLC, no M-spike/IFE) and organ response (e.g., decrease in NT-proBNP by >30%, 24-h urine protein by >50%, ALP by >50%, etc). Organ response can often be delayed by 6-12 months after hematologic response.
- Bortezomib based chemotherapy had been the standard of care, but there has been a recent change in the treatment paradigm to incorporate daratunumab. Use of daratunumab have been shown in recent studies, such as ANDROMEDA, to improve hematologic response, major organ function, and survival in AL amyloidosis.
- Novel monoclonal antibodies, such as CAEL-101, which promote the resorption of amyloid deposits are promising potential treatments for AL amyloidosis. CAEL-101 is currently being studied at Duke.
- Effective management of AL amyloidosis requires collaborative efforts across multiple disciplines.
Duke Medicine Learning, Education, and Discussion Series (LEADS) takes place each Tuesday at 12 p.m. Learn more and see schedule of upcoming sessions.