Canterbury DHB

Amyloidosis

Introduction

AL amyloidosis is a systemic disorder due to deposition of protein derived from immunoglobulin light chain fragments. It complicates myeloma in around 10% of patients. Much less often it can occur with Waldenstrom macroglobulinemia or NHL.

Clinical features

Although almost all patients have multisystem amyloid deposition, it is not uncommon to present with evidence of mainly one organ affected.

Common presentations include:

• Nephrotic syndrome
• Restrictive cardiomyopathy
• Peripheral neuropathy
• Hepatomegaly with elevated ALT/AST
• Macroglossia and involvement of other muscles
• Purpura and other skin manifestations
• Bleeding diathesis
• Manifestations of myeloma

Diagnosis

Choosing a biopsy site – abdominal fat biopsy and bone marrow biopsy are recommended as part of initial evaluation due to ease, convenience, and yield taking into account expected yield and risks. Other common sites of involvement are rectum and skin.

Bone marrow biopsy and skeletal survey as for investigation of myeloma.

Evaluation of organ involvement

Renal: 24-hour urine for protein electropheresis, creatinine, GFR and albumin.

Heart: seated and standing BP, troponin T, NT-proBNP, echocardiogram, ECG and if abnormal consider MRI.

Coagulation: coagulation screen and factor X if bleeding or abnormal screen.

Neuropathy: if symptomatic consider EMG and nerve conduction studies.

Management

The general goal of therapy is to decrease amyloid production, limit further organ damage, and allow for regression of tissue amyloid deposits. Regression of amyloid in tissue is uncommon and symptoms are likely not reversible.

Consider referral and involvement of other specialists based on pattern of organ involvement.

Transplant eligibility

Assess all patients below 70 years to determine eligibility for autologous transplantation. See section on Stem Cell Transplantation and referral.

Induction therapy before transplant or for transplant ineligible patients is generally with a bortezomib-based regimen. Thalidomide and lenalidomide are less well tolerated than in myeloma patients.

1st line therapy

There are no randomised trials comparing melphalan and prednisone with bortezomib-based regimens. However, due to the rapid reduction in the production of light chain seen with bortezomib this has become more frequently used. For a fuller discussion, refer to UpToDate or review articles linked below.

Further reading

• Palladini, G. and G. Merlini (2016). "What is new in diagnosis and management of light chain amyloidosis?" Blood 128(2): 159-168.
• Wechalekar, A. D., et al. (2015). "Guidelines on the management of AL amyloidosis." Br J Haematol 168(2): 186-206.
• Manwani, R., et al. (2019). "A prospective observational study of 915 patients with systemic AL amyloidosis treated with upfront bortezomib." Blood 134(25): 2271-2280.

ASCT for AL amyloidosis

• Varga, C. and R. L. Comenzo (2019). "High-dose melphalan and stem cell transplantation in systemic AL amyloidosis in the era of novel anti-plasma cell therapy: a comprehensive review." Bone Marrow Transplant 54(4): 508-518.
• Minnema, M. C., et al. (2019). "Bortezomib based induction followed by stem cell transplantation in light chain amyloidosis: results of the multicenter HOVON 104 trial." Haematologica 104(11): 2274-2282.
• Sher, T., et al. (2016). "Evolution of Hematopoietic Cell Transplantation for Immunoglobulin Light Chain Amyloidosis." Biol Blood Marrow Transplant 22(5): 796-801.

Topic Code: 5614