AL2019-09-22T17:36:06+00:00

AL Amyloidosis

The section Light Chain Amyloidosis is under construction and will be completed by the end of the year. A summary is presented below.

Introduction

Light chain amyloidosis (AL amyloidosis) is a clonal plasma cell disorder that is characterized by multi- organ dysfunction as a result of deposition of immunoglobulin monoclonal light chain–derived amyloid fibrils, despite low burden of plasma cells.

This website section is written as a practical localised guide for Australian haematologists diagnosing and treating AL amyloidosis. It focuses on the basic workup and principles of therapeutic decision making. We suggest referring to the Medical and Scientific Advisory Group (MSAG) clinical practice guideline “Management of Systemic AL Amyloidosis” for a more detailed discussion and therapeutic guideline.

Details of the Light Chain Amyloidosis Type

  • AL is rare
  • AL amyloidosis is usually produced by a “small but powerful” plasma cell clone
    • Less commonly it can be produced by a B-lymphoproliferative disorder (B-LPD) cell clone
  • The clinical presentation depends on the predominant organ affected
  • The most common organs involved at diagnosis are:
    • heart 74%
    • kidney 65%
    • liver 17%
    • soft tissue disease 17%
    • peripheral sensory nerves 15%
    • autonomic nerves 14 %
    • GIT 8%
  • To diagnose AL amyloidosis the following are always required
    • a biopsy showing amyloid deposition
    • monoclonal gammopathy screening
    • organ staging
  • Prognosis is primarily based on the degree of cardiac involvement as measured by cardiac biomarkers, in particular the NTproBNP.
  • Prognosis is also very dependent on haematologic outcomes.
    • Deep clonal responses (CR and VGPR) are associated with median survival outcomes of ³ 80% at two years and can even change the natural history of advanced cardiac stage AL amyloidosis
    • Hence, advanced stage disease does not preclude receiving therapy
  • Haematologic response criteria reflect the clonal response and predict survival outcomes
  • Amyloid clearance can occur if a haematologic response is achieved
  • Amyloid clearance is mediated by macrophages and is a slow process
  • Organ responses can take up to 18 months after achieving a haematologic response
  • The chances of organ amyloid clearance varies between organs;
    • Kidneys ≈ 40%
    • Liver ≈ 40%
    • Heart ≈ 20%
    • Nerves ≈ almost never recover
  • The goal of therapy is to achieve a deep enduring haematologic or clonal remission in order to effect an organ response to prolong survival and improve quality of life
  • If AL is in association with a plasma cell clone then the therapy is based on multiple myeloma regimens
  • AL patients have vital organ dysfunction and treatment is associated with increased toxicity
    • Hence most treatment regimens have been modified with a decrease in intensity and/or doses for those with AL amyloidosis
  • A haematologic CR is the ideal response goal especially if the patient has cardiac involvement
  • The initial treatment decision is between that of chemotherapy therapy vs high dose chemotherapy and autologous stem cell rescue (autoSCT)
  • Only a minority of AL patients will be eligible for autoSCT
  • The main determining factor for suitability is the degree of heart involvement
  • Bortezomib in combination with alkylator and dexamethasone is regarded as the most effective upfront chemotherapy regimen
  • Other upfront regimens include;
    • Cyclophosphamide, thalidomide and dexamethasone
    • Melphalan and Dexamethasone
    • Lenalidomide and dexamethasone.
      • These alternate regimens have comparable haematologic response rates and selection is based on toxicity, organ reserve and accessibility
  • Six cycles is recommended for non-immunomodulatory regimens
  • The goals are to achieve both a haematologic and organ response
  • If a haematologic partial response is not achieved by 2-3 cycles then a switch in therapy is recommended as ongoing treatment will not result in achievement of a VGPR/CR nor their associated significant overall survival benefits

Table. Suggested dosing for chemotherapeutic regimens for AL patients

Regimen abbreviated name Doses, route Cycle duration # cycles
CVD Bortezomib 1.3 mg/m2 s/c D1,8,15,22
dexamethasone 40mg D1, 8, 15, 22 po weekly,
cyclophosphamide 500mg po D1, 8, 15, 22
28 days 6
BMD Bortezomib 1.3 mg/m2 s/c D1,8,15,22
Melphalan 0.22mg/kg po D1, 8, 15, 22
Dexamethasone 40mg D1to D4
28 days 6
Mel-Dex Melphalan 0.22mg/kg po D1 to 4
Dexamethasone 40mg D1to D4
28 days 6
Len-Dex Lenalidomide 15 mg po D1 to D21
Dexamethasone 40mg D1, 8, 15, 22
+/-
Melphalan 0.18mg.kg/day D1 to D4
Or
Cyclophosphamide
100mg daily D1-10/ 300mg/m2 D1, 8, 15
28 Continue till PD or limiting toxicity
Pom-Dex Pomalidomide 4mg D1 to D21
Dexamethasone 40mg D1, 8, 15, 22