Amyloidosis medical therapy: Difference between revisions
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==Overview== | ==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]]. | 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 (anatomy)|organ]] damage and correcting the effects of [[organ failure]]. | ||
==Medical Therapy== | ==Medical Therapy== | ||
Some patients with primary [[amyloidosis]] respond to [[chemotherapy]] focused on the abnormal [[plasma cell]]s. A [[stem cell transplant]] may be done, as in [[multiple myeloma]]. | Some patients with primary [[amyloidosis]] respond to [[chemotherapy]] focused on the abnormal [[plasma cell]]s. A [[stem cell transplant]] may be done, as in [[multiple myeloma]]. | ||
*The initial | *The initial step in the treatment of this disorder is to correct the [[organ failure]], since the disease is discovered at an advanced stage when multiple [[organ systems]] may be affected. | ||
**[[Nephrotic syndrome]] is treated using supportive therapy and [[diuretics]]. | **[[Nephrotic syndrome]] is treated using supportive therapy and [[diuretics]]. | ||
**[[Renal failure]] is treated with [[dialysis]]. | **[[Renal failure]] is treated with [[dialysis]]. | ||
**[[Heart failure]] is treated using [[diuretics]]. | **[[Heart failure]] is treated using [[diuretics]]. | ||
**Gastrointestinal and nerve involvement are treated symptomatically. | **[[Gastrointestinal tract|Gastrointestinal]] and [[nerve]] involvement are treated [[Symptomatic|symptomatically]]. | ||
The most commonly used regimen for AL amyloidosis is CyBorD, which consists of cyclophosphamide, bortezomib, and dexamethasone.<ref name="pmid29854961">{{cite journal| author=Milani P, Merlini G, Palladini G| title=Novel Therapies in Light Chain Amyloidosis. | journal=Kidney Int Rep | year= 2018 | volume= 3 | issue= 3 | pages= 530-541 | pmid=29854961 | doi=10.1016/j.ekir.2017.11.017 | pmc=5976806 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29854961 }} </ref> | |||
The most commonly used regimen for AL amyloidosis is CyBorD, which consists of [[cyclophosphamide]], [[bortezomib]], and [[dexamethasone]].<ref name="pmid29854961">{{cite journal| author=Milani P, Merlini G, Palladini G| title=Novel Therapies in Light Chain Amyloidosis. | journal=Kidney Int Rep | year= 2018 | volume= 3 | issue= 3 | pages= 530-541 | pmid=29854961 | doi=10.1016/j.ekir.2017.11.017 | pmc=5976806 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29854961 }} </ref> | |||
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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | ||
Bortezomib | [[Bortezomib]] | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Reversibly inhibits the 26S proteasome, preventing recycling of proteins and inducing cell cycle arrest and apoptosis | *Reversibly inhibits the 26S [[proteasome]], preventing recycling of [[proteins]] and inducing [[cell cycle]] arrest and [[apoptosis]] | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Cycles 1-4: 1.3mg/m2 IV/SC on days 1, 4, 8, 11, 22, 25, 29, 32 | *Cycles 1-4: 1.3mg/m2 [[Intravenous|IV]]/[[Subcutaneous|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 | *Cycles 5-9: 1.3mg/m2 [[Intravenous|IV]]/[[Subcutaneous|SC]] on days 1, 8, 22, 29 | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
Peripheral neuropathy, VZV reactivation, hepatic impairment, asthenia, diarrhea, nausea, constipation, arthralgia, edema, dizziness | [[Peripheral neuropathy]], [[Varicella zoster virus|VZV]] reactivation, [[hepatic impairment]], [[asthenia]], [[diarrhea]], [[nausea]], [[constipation]], [[arthralgia]], [[edema]], [[dizziness]] | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | ||
Dexamethasone | [[Dexamethasone]] | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Suppresses polymorphonuclear leukocytes | *Suppresses [[polymorphonuclear leukocytes]] | ||
*Inhibits prostaglandins and proinflammatory cytokines | *Inhibits [[prostaglandins]] and [[proinflammatory]] [[cytokines]] | ||
*Suppresses lymphocyte proliferation | *Suppresses [[lymphocyte]] proliferation | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*40mg PO weekly | *40mg [[Oral|PO]] weekly | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
Infections, immunosuppression, bone loss, cataract formation, glaucoma, muscular atrophy | [[Infections]], [[immunosuppression]], [[bone loss]], [[cataract]] formation, [[glaucoma]], [[muscular]] [[atrophy]] | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | ||
Melphalan | [[Melphalan]] | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Inhibits DNA and RNA synthesis | *Inhibits [[DNA]] and [[RNA]] synthesis | ||
*Crosslinks DNA and causes DNA replication failure | *[[Crosslinking of DNA|Crosslinks DNA]] and causes [[DNA replication]] failure | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*6mg PO daily for 2-3 weeks, OR | *6mg [[Oral|PO]] daily for 2-3 weeks, OR | ||
*10mg PO daily for 7-10 days, OR | *10mg [[Oral|PO]] daily for 7-10 days, OR | ||
*0.15mg/kg daily PO for 7 days, THEN | *0.15mg/kg daily [[Oral|PO]] for 7 days, THEN | ||
*1-3mg or 0.05mg/kg PO daily after counts recover | *1-3mg or 0.05mg/kg [[Oral|PO]] daily after counts recover | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
Myelosuppression, nausea, vomiting, pulmonary fibrosis, stomatitis | [[Myelosuppression]], [[nausea]], [[vomiting]], [[pulmonary fibrosis]], [[stomatitis]] | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | ||
Cyclophosphamide | [[Cyclophosphamide]] | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Alkylating agent | *[[Alkylating agent]] | ||
*Crosslinks DNA and causes DNA replication failure | *[[Crosslinking of DNA|Crosslinks DNA]] and causes [[DNA replication]] failure | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*40-50mg/kg weekly | *40-50mg/kg weekly | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
Myelosuppression, nausea, vomiting, hemorrhagic cystitis, secondary malignancies | [[Myelosuppression]], [[nausea]], [[vomiting]], [[hemorrhagic cystitis]], secondary [[malignancies]] | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | ||
Patisiran<ref name="pmid28893208">{{cite journal| author=Adams D, Suhr OB, Dyck PJ, Litchy WJ, Leahy RG, Chen J et al.| title=Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. | journal=BMC Neurol | year= 2017 | volume= 17 | issue= 1 | pages= 181 | pmid=28893208 | doi=10.1186/s12883-017-0948-5 | pmc=5594468 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28893208 }} </ref> | [[Patisiran]]<ref name="pmid28893208">{{cite journal| author=Adams D, Suhr OB, Dyck PJ, Litchy WJ, Leahy RG, Chen J et al.| title=Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. | journal=BMC Neurol | year= 2017 | volume= 17 | issue= 1 | pages= 181 | pmid=28893208 | doi=10.1186/s12883-017-0948-5 | pmc=5594468 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28893208 }} </ref> | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*RNA interference therapy | *[[RNA interference]] therapy | ||
*Inhibits hepatic synthesis of transthyretin | *Inhibits [[hepatic]] synthesis of [[transthyretin]] | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*0.3mg/kg weekly | *0.3mg/kg weekly | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
Dyspepsia, dyspnea, erythema, bronchitis, blurry vision | [[Dyspepsia]], [[dyspnea]], [[erythema]], [[bronchitis]], [[blurry vision]] | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | ||
Daratumumab<ref name="pmid26864107">{{cite journal| author=van de Donk NW, Janmaat ML, Mutis T, Lammerts van Bueren JJ, Ahmadi T, Sasser AK et al.| title=Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. | journal=Immunol Rev | year= 2016 | volume= 270 | issue= 1 | pages= 95-112 | pmid=26864107 | doi=10.1111/imr.12389 | pmc=4755228 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26864107 }} </ref> | [[Daratumumab]]<ref name="pmid26864107">{{cite journal| author=van de Donk NW, Janmaat ML, Mutis T, Lammerts van Bueren JJ, Ahmadi T, Sasser AK et al.| title=Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. | journal=Immunol Rev | year= 2016 | volume= 270 | issue= 1 | pages= 95-112 | pmid=26864107 | doi=10.1111/imr.12389 | pmc=4755228 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26864107 }} </ref> | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Anti-CD38 monoclonal antibody | *Anti-CD38 monoclonal antibody | ||
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*16mg/kg weekly for weeks 1-8, then every 2 weeks for weeks 9-24, then every 4 weeks thereafter | *16mg/kg weekly for weeks 1-8, then every 2 weeks for weeks 9-24, then every 4 weeks thereafter | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
Anemia, neutropenia, false positive indirect Coomb's test, infusion reaction, lymphopenia | [[Anemia]], [[neutropenia]], [[false positive]] [[Indirect Coombs test|indirect Coomb's test]], [[infusion reaction]], [[lymphopenia]] | ||
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Treatment options with limited success include [[melphalan]], [[prednisone]], and [[colchicine]]. | Treatment options with limited success include [[melphalan]], [[prednisone]], and [[colchicine]]. | ||
In secondary [[amyloidosis]], aggressively treating the disease that is causing the excess [[amyloid]] protein can improve symptoms and/or slow the disease from getting worse. Complications such as [[heart failure]], [[renal failure]], and other problems can sometimes be treated, when needed. | In secondary [[amyloidosis]], aggressively treating the disease that is causing the excess [[amyloid]] protein can improve [[symptoms]] and/or slow the disease from getting worse. Complications such as [[heart failure]], [[renal failure]], and other problems can sometimes be treated, when needed. | ||
== References == | == References == |
Revision as of 01:14, 26 October 2019
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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
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 initial step in the treatment of this disorder is to correct the organ failure, since the disease is discovered at an advanced stage when multiple organ systems may be affected.
- Nephrotic syndrome is treated using supportive therapy and diuretics.
- Renal failure is treated with dialysis.
- Heart failure is treated using diuretics.
- Gastrointestinal and nerve involvement are treated symptomatically.
The most commonly used regimen for AL amyloidosis is CyBorD, which consists of cyclophosphamide, bortezomib, and dexamethasone.[1]
Treatment options with limited success include melphalan, prednisone, and colchicine.
In secondary amyloidosis, aggressively treating the disease that is causing the excess amyloid protein can improve symptoms and/or slow the disease from getting worse. Complications such as heart failure, renal failure, and other problems can sometimes be treated, when needed.
References
- ↑ 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.
- ↑ 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.
- ↑ 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.