Amyloidosis
GENERAL PRINCIPLES
Primary (AL) amyloidosis is an infiltrative disorder due to monoclonal, light chain deposition in various tissues most often involving the kidney (renal failure, nephrotic syndrome), heart (nonischemic cardiomyopathy), peripheral nervous system (neuropathy), and GI tract/liver (macroglossia, diarrhea, nausea, vomiting).
Unexplained findings in any of these organ systems should prompt evaluation for amyloidosis. Primary AL amyloidosis must be distinguished from nonclonal secondary systemic amyloidosis.Diagnosis and Treatment
• SPEP, UPEP, and serum free light chains may detect an M protein or an abnormal free light chain ratio that is found in gt;90% of patients with AL amyloidosis. In the absence of a measurable M protein, consider other types of secondary systemic amyloidosis. In addition to Congo red staining for amyloid in the BM or other affected tissue, mass spectroscopy to identify the presence of light chains establishes the diagnosis of AL amyloidosis. An NT-proBNP, troponin T or I, and 24-hour urinary protein are important in assessing organ involvement and staging.
• Several effective chemotherapy regimens have been developed during the last decade, including bortezomib-based regimens such as CyBorD (cyclophosphamide, bortezomib, dexamethasone).30 Additionally, those with adequate organ function and a good performance status should be considered for autologous stem cell transplant (auto-SCT).
• Daratumumab, an anti-CD38 monoclonal antibody approved for the treatment of multiple myeloma, has demonstrated efficacy in AL amyloid and has been used off label for relapsed systemic AL amyloidosis.31
• Treatment of amyloidosis remains difficult, and progressive organ failure is frequent. Cardiac involvement generally portends the worst prognosis.