Primary Systemic Amyloidosis Medication
- Author: Judit Nyirady, MD, MBA; Chief Editor: Dirk M Elston, MD more...
The treatment of primary systemic amyloidosis is often unsatisfactory. No reliable method for the accurate assessment of the total amount of amyloid in the body exists. Investigations are limited to the evaluation of organ function and the measurement of monoclonal protein levels in the serum and urine.
The similarity between primary systemic amyloidosis and multiple myeloma suggests that chemotherapy may be useful. Using different regimens of intermittent oral melphalan and prednisone, 2 groups of investigators[12, 22] confirmed the effectiveness of this therapy compared with no therapy or therapy with colchicine alone. However, the response rate was low, with an increased survival from a median of approximately 7-9 months in patients who did not receive chemotherapy to approximately 12-18 months in those receiving chemotherapy.
In another trial, Kyle and Greipp reported the effectiveness of combined melphalan and prednisone therapy compared with placebo therapy. Although the nephrotic syndrome improved in a number of individuals receiving the active medications, overall survival rates for the active and placebo groups were not substantially different.
Colchicine has also been used in the treatment of primary systemic amyloidosis. Colchicine may inhibit amyloid deposition by blocking the formation of amyloid-enhancing factors, and it also inhibits the secretion of amyloid from hepatocytes.
Based on encouraging results in myeloma patients, Dispenzieri et al reported results of a clinical trial of lenalidomide therapy with or without dexamethasone in patients with primary systemic amyloidosis. As a single agent, lenalidomide had modest activity in primary systemic amyloidosis. This activity was significantly enhanced when lenalidomide was used in conjunction with dexamethasone.
These agents inhibit key factors in the immune system that are responsible for inflammatory responses.
Prednisone is an immunosuppressant for the treatment of autoimmune disorders; it may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.
Dexamethasone has many pharmacologic benefits but also significant adverse effects. It stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, and inhibits prostaglandin and proinflammatory cytokines (eg, TNF-alpha, IL-6, IL-2, and IFN-gamma). The inhibition of chemotactic factors and factors that increase capillary permeability inhibits recruitment of inflammatory cells into affected areas. Dexamethasone suppresses lymphocyte proliferation through direct cytolysis and inhibits mitosis. It breaks down granulocyte aggregates and improves pulmonary microcirculation. It is an important chemotherapeutic agent in the treatment of ALL. It is used in induction and reinduction therapy and given as intermittent pulses during continuation therapy.
Adverse effects are hyperglycemia, hypertension, weight loss, GI bleeding or perforation synthesis, cerebral palsy, adrenal suppression, and death. Most of the adverse effects of corticosteroids are dose or duration dependent.
Dexamethasone is readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. It lacks the salt-retaining property of hydrocortisone.
Patients can be switched from an intravenous to oral regimen in a 1:1 ratio.
These agents inhibit cell growth and proliferation.
Melphalan inhibits mitosis by cross-linking DNA strands.
These agents may inhibit the events involved in the inflammatory response associated with the disease.
Colchicine decreases leukocyte motility and phagocytosis in inflammatory responses.
Lenalidomide is structurally similar to thalidomide. It elicits immunomodulatory and antiangiogenic properties. It inhibits proinflammatory cytokine secretion and increases anti-inflammatory cytokines from peripheral blood mononuclear cells.
Hayman SR, Bailey RJ, Jalal SM, et al. Translocations involving the immunoglobulin heavy-chain locus are possible early genetic events in patients with primary systemic amyloidosis. Blood. 2001 Oct 1. 98(7):2266-8. [Medline].
Divry P, Florkin M, Firket J. Sur les proprietes otiques de l'amiloide. C R Soc Biol (Paris). 1927. 97:1808-10.
Cohen AS, Calkins E. Electron microscopic observations on a fibrous component in amyloid of diverse origins. Nature. 1959 Apr 25. 183(4669):1202-3. [Medline].
Murtagh B, Hammill SC, Gertz MA, Kyle RA, Tajik AJ, Grogan M. Electrocardiographic findings in primary systemic amyloidosis and biopsy-proven cardiac involvement. Am J Cardiol. 2005 Feb 15. 95(4):535-7. [Medline].
Wong CK. Mucocutaneous manifestations in systemic amyloidosis. Clin Dermatol. 1990 Apr-Jun. 8(2):7-12. [Medline].
Silverstein SR. Primary, systemic amyloidosis and the dermatologist: where classic skin lesions may provide the clue for early diagnosis. Dermatol Online J. 2005. 11(1):5. [Medline].
McCormick RS, Sloan P, Farr D, Carrozzo M. Oral puprura as the first manifestation of primary systemic amyloidosos. Br J Oral Maxillofac Surg. 2015 Dec 17. [Medline].
Iwahashi N, Tame E, Nagasaka T, Furuta M, Nagashima H, Nimura Y. Massive hemorrhage and pseudo-obstruction of the small intestine caused by primary AL amyloidosis associated with gastric cancer: report of a case. Surg Today. 2004. 34(10):871-4. [Medline].
Kyle RA, Bayrd ED. Amyloidosis: Review of 236 cases. Medicine (Baltimore). 1975. 54:271-299. [Medline].
Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc. 1983 Oct. 58(10):665-83. [Medline].
Roy A, Roy V. Primary systemic amyloidosis. Early diagnosis and therapy can improve survival rates and quality of life. Postgrad Med. 2006 Jun-Jul. 119(1):93-9. [Medline].
Skinner M, Anderson J, Simms R, et al. Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone, and colchicine versus colchicine only. Am J Med. 1996 Mar. 100(3):290-8. [Medline].
Buss SJ, Emami M, Mereles D, Korosoglou G, Kristen AV, Voss A, et al. Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers. J Am Coll Cardiol. 2012 Sep 18. 60(12):1067-76. [Medline].
Lutz ME, Pittelkow MR. Progressive generalized alopecia due to systemic amyloidosis. J Am Acad Dermatol. 2002 Mar. 46(3):434-6. [Medline].
Moura CG, Moura TG, Duraes AR, Souza SP. Exuberant macroglossia in a patient with primary systemic amyloidosis. Clin Exp Rheumatol. 2005 May-Jun. 23(3):428. [Medline].
Xavier SD, Bussoloti IF, Muller H. Macroglossia secondary to systemic amyloidosis: case report and literature review. Ear Nose Throat J. 2005 Jun. 84(6):358-61. [Medline].
Summers EM, Kendrick CG. Primary localized cutaneous nodular amyloidosis and CREST syndrome: a case report and review of the literature. Cutis. 2008 Jul. 82(1):55-9. [Medline].
Villa F, Dionigi G, Tanda ML, Rovera F, Boni L. Amyloid goiter. Int J Surg. 2008 Dec 13. [Medline].
Terrier B, Jaccard A, Harousseau JL, et al. The clinical spectrum of IgM-related amyloidosis: a French nationwide retrospective study of 72 patients. Medicine (Baltimore). 2008 Mar. 87(2):99-109. [Medline].
Lee JH, Lee GY, Kim SJ, Kim KH, Jeon ES, Lee KH, et al. Imaging Findings and Literature Review of (18)F-FDG PET/CT in Primary Systemic AL Amyloidosis. Nucl Med Mol Imaging. 2015 Sep. 49(3):[Medline].
Picken MM. Modern approaches to the treatment of amyloidosis: the critical importance of early detection in surgical pathology. Adv Anat Pathol. 2013 Nov. 20(6):424-39. [Medline].
Kyle RA, Gertz MA, Greipp PR, et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med. 1997 Apr 24. 336(17):1202-7. [Medline].
Shimojima Y, Matsuda M, Ishii W, et al. High-dose melphalan followed by autologous stem cell support in primary systemic AL amyloidosis with multiple organ involvement. Intern Med. 2005 May. 44(5):484-9. [Medline].
Singh V, Fishman JE, Alfonso CE. Primary Systemic Amyloidosis Presenting as Constrictive Pericarditis. Cardiology. 2011 Jul 12. 118(4):251-255. [Medline].
Desai HV, Aronow WS, Peterson SJ, Frishman WH. Cardiac amyloidosis: approaches to diagnosis and management. Cardiol Rev. 2010 Jan-Feb. 18(1):1-11. [Medline].
Hayman SR, Lacy MQ, Kyle RA, Gertz MA. Primary systemic amyloidosis: a cause of malabsorption syndrome. Am J Med. 2001 Nov. 111(7):535-40. [Medline].
Kyle RA, Greipp PR. Primary systemic amyloidosis: comparison of melphalan and prednisone versus placebo. Blood. 1978 Oct. 52(4):818-27. [Medline].
Dispenzieri A, Lacy MQ, Zeldenrust SR. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2006 Sep 28. [Medline].