Amyloidosis medical therapy

Jump to navigation Jump to search

Amyloidosis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Primary amyloidosis
Secondary amyloidosis
Familial amyloidosis
Wild-type (senile) amyloidosis
Cardiac amyloidosis
Beta-2 microglobulin related amyloidosis
Gelsolin related amyloidosis
Lysozyme amyloid related amyloidosis
Leucocyte cell-derived chemotaxin 2 related amyloidosis
Fibrinogen A alpha-chain associated amyloidosis

Pathophysiology

Causes

Differentiating Amyloidosis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Amyloidosis medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Amyloidosis medical therapy

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Amyloidosis medical therapy

CDC on Amyloidosis medical therapy

Amyloidosis medical therapy in the news

Blogs on Amyloidosis medical therapy

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for Amyloidosis medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]; Associate Editor(s)-in-Chief:

Overview

There are few available treatments for primary amyloidosis. Since the disease is typically discovered at an advanced stage, the initial treatment is aimed at preventing further organ damage and correcting the effects of organ failure.

Medical Therapy

AL Amyloidosis:

Some patients with primary amyloidosis respond to chemotherapy focused on the abnormal plasma cells. A stem cell transplant may be done, as in multiple myeloma.

The most commonly used regimen for AL amyloidosis is CyBorD, which consists of cyclophosphamide, bortezomib, and dexamethasone.[1]

Therapy Mechanism of Action Dosing Adverse Effects

Bortezomib

  • Cycles 1-4: 1.3mg/m2 IV/SC on days 1, 4, 8, 11, 22, 25, 29, 32
  • Cycles 5-9: 1.3mg/m2 IV/SC on days 1, 8, 22, 29

Peripheral neuropathy, VZV reactivation, hepatic impairment, asthenia, diarrhea, nausea, constipation, arthralgia, edema, dizziness

Dexamethasone

  • 40mg PO weekly

Infections, immunosuppression, bone loss, cataract formation, glaucoma, muscular atrophy

Melphalan

  • 6mg PO daily for 2-3 weeks, OR
  • 10mg PO daily for 7-10 days, OR
  • 0.15mg/kg daily PO for 7 days, THEN
  • 1-3mg or 0.05mg/kg PO daily after counts recover

Myelosuppression, nausea, vomiting, pulmonary fibrosis, stomatitis

Cyclophosphamide

  • 40-50mg/kg weekly

Myelosuppression, nausea, vomiting, hemorrhagic cystitis, secondary malignancies

Patisiran[2]

  • 0.3mg/kg weekly

Dyspepsia, dyspnea, erythema, bronchitis, blurry vision

Daratumumab[3]

  • Anti-CD38 monoclonal antibody
  • Depletes B lymphocytes and plasma cells
  • 16mg/kg weekly for weeks 1-8, then every 2 weeks for weeks 9-24, then every 4 weeks thereafter

Anemia, neutropenia, false positive indirect Coomb's test, infusion reaction, lymphopenia


Treatment options with limited success include melphalan, prednisone, and colchicine.

AA Amyloidosis:

  • Medical or surgical treatment of the underlying chronic infection or inflammatory disease is recommended among all patients who develop AA amyloidosis.
  • Aggressively treating the disease that is causing the excess amyloid protein can improve symptoms and slow down or halt the progression of the disease.
  • Complications such as heart failure, renal failure, and other problems can sometimes be treated, when needed.
  • Although the choice of therapy depends on the underlying cause of chronic inflammation, the aim is always to suppress production of SAA to within the normal range.


Underlying Condition Treatment Options Examples
Inflammatory arthritis Conventional disease-modifying agents
  • Gold
  • Hydroxychloroquine sulfasalazine
  • Azathioprine
  • Methotrexate

Other immunosuppressant agents

  • Cyclosporine
  • Cyclophosphamide
  • Mycophenolate
  • Leflunomide

Biologic agents

  • Infliximab
  • Etanercept
  • Adalimumab
  • Tocilizumab
  • Rituximab
Periodic fevers On-demand agents
  • Nonsteroidal anti-inflammatory drugs
  • Prednisone

Colchicine

Colchicine

Biologic agents

  • Anakinra
  • Canakinumab



  • Long-term inflammatory control can be accompanied by gradual regression of amyloid deposits and improvement in renal function.
  • Currently a second clinical trial is in progress in order to evaluate a targeted inhibitor molecule, Kiacta, in the management of secondary amyloidosis.
  • Novel therapies aimed at promoting clearance of existing amyloid deposits soon may be an effective treatment approach.


References

  1. Milani P, Merlini G, Palladini G (2018). "Novel Therapies in Light Chain Amyloidosis". Kidney Int Rep. 3 (3): 530–541. doi:10.1016/j.ekir.2017.11.017. PMC 5976806. PMID 29854961.
  2. Adams D, Suhr OB, Dyck PJ, Litchy WJ, Leahy RG, Chen J; et al. (2017). "Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy". BMC Neurol. 17 (1): 181. doi:10.1186/s12883-017-0948-5. PMC 5594468. PMID 28893208.
  3. van de Donk NW, Janmaat ML, Mutis T, Lammerts van Bueren JJ, Ahmadi T, Sasser AK; et al. (2016). "Monoclonal antibodies targeting CD38 in hematological malignancies and beyond". Immunol Rev. 270 (1): 95–112. doi:10.1111/imr.12389. PMC 4755228. PMID 26864107.

Template:WH Template:WS