Primary amyloidosis medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{Primary amyloidosis}}
{{Primary amyloidosis}}
{{CMG}}; {{AE}}
{{CMG}}; {{AE}} {{shyam}}


==Overview==
==Overview==


==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]].
*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 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>
{|
| valign="top" |
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! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Therapy}}
! style="background: #4479BA; width: 400px;" |{{fontcolor|#FFF|Mechanism of Action}}
! style="background: #4479BA; width: 400px;" |{{fontcolor|#FFF|Dosing}}
! style="background: #4479BA; width: 400px;" |{{fontcolor|#FFF|Adverse Effects}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
[[Bortezomib]]
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*Reversibly inhibits the 26S [[proteasome]], preventing recycling of [[proteins]] and inducing [[cell cycle]] arrest and [[apoptosis]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*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 [[Intravenous|IV]]/[[Subcutaneous|SC]] on days 1, 8, 22, 29
| style="padding: 5px 5px; background: #F5F5F5;" |
[[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" |
[[Dexamethasone]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*Suppresses [[polymorphonuclear leukocytes]]
*Inhibits [[prostaglandins]] and [[proinflammatory]] [[cytokines]]
*Suppresses [[lymphocyte]] proliferation
| style="padding: 5px 5px; background: #F5F5F5;" |
*40mg [[Oral|PO]] weekly
| style="padding: 5px 5px; background: #F5F5F5;" |
[[Infections]], [[immunosuppression]], [[bone loss]], [[cataract]] formation, [[glaucoma]], [[muscular]] [[atrophy]]
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
[[Melphalan]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*Inhibits [[DNA]] and [[RNA]] synthesis
*[[Crosslinking of DNA|Crosslinks DNA]] and causes [[DNA replication]] failure
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*6mg [[Oral|PO]] daily for 2-3 weeks, OR
*10mg [[Oral|PO]] daily for 7-10 days, OR
*0.15mg/kg daily [[Oral|PO]] for 7 days, THEN
*1-3mg or 0.05mg/kg [[Oral|PO]] daily after counts recover
| style="padding: 5px 5px; background: #F5F5F5;" |
[[Myelosuppression]], [[nausea]], [[vomiting]], [[pulmonary fibrosis]], [[stomatitis]]
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
[[Cyclophosphamide]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Alkylating agent]]
*[[Crosslinking of DNA|Crosslinks DNA]] and causes [[DNA replication]] failure
| style="padding: 5px 5px; background: #F5F5F5;" |
*40-50mg/kg weekly
| style="padding: 5px 5px; background: #F5F5F5;" |
[[Myelosuppression]], [[nausea]], [[vomiting]], [[hemorrhagic cystitis]], secondary [[malignancies]]
|-
| 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>
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[RNA interference]] therapy
*Inhibits [[hepatic]] synthesis of [[transthyretin]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*0.3mg/kg weekly
| style="padding: 5px 5px; background: #F5F5F5;" |
[[Dyspepsia]], [[dyspnea]], [[erythema]], [[bronchitis]], [[blurry vision]]
|-
| 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>
| style="padding: 5px 5px; background: #F5F5F5;" |
*Anti-CD38 monoclonal antibody
*Depletes B lymphocytes and plasma cells
| style="padding: 5px 5px; background: #F5F5F5;" |
*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;" |
[[Anemia]], [[neutropenia]], [[false positive]] [[Indirect Coombs test|indirect Coomb's test]], [[infusion reaction]], [[lymphopenia]]
|-
|}


==References==
==References==

Revision as of 01:55, 30 October 2019

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

Overview

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 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

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.

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