Waldenström's macroglobulinemia medical therapy: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
 
(52 intermediate revisions by 6 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Waldenström's macroglobulinemia}}
{{Waldenström's macroglobulinemia}}
{{CMG}}
{{CMG}}; {{AE}} {{S.M.}}, {{MGS}}, {{RAK}}; {{GRR}} {{Nat}}
==Overview==
==Overview==
[[Risk stratification tools|Risk stratification]] determines the [[Protocol (natural sciences)|protocol]] of management used for [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]]. There is no [[Treatments|treatment]] for [[asymptomatic]] [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]]. The mainstay of [[Treatments|treatment]] for [[symptomatic]] [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]] is [[Rituximab]] +/- [[Chemotherapy]]. [[Hyperviscosity syndrome]] is a [[medical emergency]] and requires [[prompt]] [[Treatments|treatment]] with [[plasmapheresis]]. [[Drug]] of choice for the [[Treatments|treatment]] of [[Bing-Neel syndrome|bing-neel syndrome]] is [[Ibrutinib]] with or without concurrent [[rituximab]]. Other [[Treatments|treatment]] options include [[targeted therapy]], [[immunotherapy]] and [[radiation therapy]].
==Medical Therapy==
==Medical Therapy==
There is no single accepted treatment for WM. Indeed, in 1991, Waldenström himself raised the question of the need for effective therapy.<ref>{{cite journal | author=Waldenstrom J | title=To treat or not to treat, this is the real question | journal=Leuk Res | year=1991 | pages=407-8 | volume=15 | issue=6  | id=PMID 1907339}}</ref> In the absence of symptoms, many clinicians will recommend simply monitoring the patient.
There's no [[cure]] for WM with [[current]] [[Therapy|therapies]]. Instead, the [[Treatments|treatment]] [[Goal-directed therapy|goals]] are to [[control]] [[symptoms]] and [[Prevention (medical)|prevent]] [[End organ damage|end-organ damage]], while [[Maximum|maximizing]] [[quality of life]]. There is no [[standard]] [[therapy]] for the [[Treatments|treatment]] of WM. While various [[drugs]] and [[Combination therapy|combinations]] have demonstrated to have provided [[clinical]] benefit, hence, there are several different options for [[Treatments|treating]] [[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]] [[Dependent variable|depending]] on [[Staging (pathology)|stage]] of the [[disease]]:<ref name="Tx">Lymphoplasmacytic lymphoma. Canadian Cancer Society 2015. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/lymphoplasmacytic-lymphoma/?region=ab Accessed on November 6 2015 </ref>
{| class="wikitable"
|+Summary of how to approach different patients with Waldenstrom's macroglobulinemia
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Patient's condition/parameters}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|How to proceed accordingly}}
|-
|
* [[Immunoglobulin M|IgM]] [[MGUS]] (<10% lymphoplasmacytic [[Infiltration (medical)|infiltrate]])
* Smoldering/[[asymptomatic]] [[lymphoplasmacytic lymphoma|Waldenstrom's macroglobulinemia]]
* [[Hemoglobin]] < or = 11g/dl
* [[Platelets]] > or = 120x10*9 /L
|[[Observation]]
|-
|
* [[Symptomatic]] LPL [[patient]]
* [[Hemoglobin]] <11g/dl
* [[Platelets]] <120x10*9 /L
* [[IgM]]-related [[neuropathy]]
* [[Hemolytic anemia]] [[Association (statistics)|associated]] with [[Waldenström's macroglobulinemia|Waldenstrom macroglobulinemia]]
|
*[[Treatments|Treat]] with single [[Agent study|agent]], [[rituximab]] (one [[Cycle (gene)|cycle]] only, no [[Maintenance dose|maintenance]] [[therapy]] required)
* [[Plasmapheresis]] in [[Case-based reasoning|case]] of occurrence of [[hyperviscosity]] with [[Treatments|treatment]]
|-
|
*[[Bulk density|Bulky]] [[disease]]
* [[Hemoglobin]] < or = 10g/dl
* [[Platelets]] < 100x10*9/L
* Constitutional [[symptoms]]
* [[Hyperviscosity syndrome]]
|Hperviscosity present:
* [[Plasmapheresis]] and DRC ([[dexamethasone]] + [[rituximab]] + [[cyclophosphamide]])
[[Hyperviscosity]] absent:
* DRC only
|-
|
* [[Patient]] with [[relapse]] of [[lymphoplasmacytic lymphoma|Waldenstrom's macroglobulinemia]] (mSMART [[Guideline (medical)|guidelines]])
|Consider [[clinical trial]] + [[stem cell transplant]] in selected [[patients]]:
 
* If the [[length]] of [[Response element|response]] to initial [[therapy]] is = or >2 [[Year|years]], [[Repeatability|repeat]] the same [[First-line therapy|first-line]] [[Agent study|agent]] as used before
* If the [[length]] of [[Response element|response]] to initial [[therapy]] is <2 years, use an [[Alternative medicine|alternative]] [[First-line therapy|first-line]] [[Agent study|agent]]
|}
 
====Watchful waiting/active surveillance for asymptomatic patients with WM====
There is no [[Treatments|treatment]] for [[asymptomatic]] [[patients]] with WM. As WM [[Development|develops]] [[Slow|slowly]] and may not need to be [[Treatments|treated]] right away, it is [[Monitor unit|monitored]] by [[Health care|healthcare]] team every 3-6 months which is known as [[watchful waiting]]/active surveillance and [[Treatments|treatment]] is started when [[symptoms]] [[Appearance|appear]], such as [[hyperviscosity syndrome]], or there are [[signs]] that the [[disease]] is progressing more quickly.<ref name="BM">Waldenström's macroglobulinemia. Patient (2015)http://patient.info/doctor/waldenstroms-macroglobulinaemia-pro Accessed on November 10, 2015</ref> Active surveillance includes [[Monitoring competence|monitoring]] of the following [[laboratory]] [[Parameter|parameters]]:
*[[Complete blood count]] ([[Complete blood count|CBC]]) with [[Difference (philosophy)|differential]]
*Complete [[metabolic]] [[Panel analysis|panel]] ([[CMP-N-acetylneuraminate monooxygenase|CMP]])
*[[Immunoglobulin]] levels in the [[serum]] ([[quantitative]])
*[[Serum protein electrophoresis]]
 
====Symptomatic patients with WM====
[[Symptomatic]] [[patients]] with WM are started on [[chemotherapy]] depending on the [[Staging (pathology)|stage]].<ref name="ADR">Waldenström's macroglobulinemia: prognosis and management. Blood Cancer Journal (2015)http://www.nature.com/bcj/journal/v5/n3/full/bcj201528a.html Accessed on November 13, 2015</ref>
 
*Initial [[Staging (pathology)|stage]] of WM is [[Association (statistics)|associated]] with:
 
:*[[Neuropathy]]
:*[[Anemia]] or [[cytopenias]]
:*Low-[[volume]] [[Nodal (protein)|nodal]] involvement
:*[[Asymptomatic]] [[splenomegaly]]
 
*Late [[Staging (pathology)|stage]] of WM is [[Association (statistics)|associated]] with:
:*[[Adenopathy]]
:*[[Symptomatic]] [[splenomegaly]]
:*[[Cytopenia|Cytopenias]]
:*[[Hyperviscosity syndrome]]
:*[[Neuropathy]]
:*Constitutional [[symptoms]]
*[[Men]] and [[Womens Pack|women]] with childbearing [[potential]] should receive [[counseling]] about the [[potential]] [[Effect size|effect]] of [[Treatments|treatment]] on their [[fertility]] and options for [[fertility]]-[[Preservative|preserving]] [[Measure (mathematics)|measures]].


In 2002, a panel at the International Workshop on Waldenström's Macroglobulinemia agreed on criteria for the initiation of therapy. They recommended starting therapy in patients with constitutional symptoms such as recurrent [[fever]], [[night sweats]], [[fatigue]] due to [[anemia]], [[weight loss]], progressive symptomatic [[lymphadenopathy]] or [[splenomegaly]], and [[anemia]] due to [[bone marrow]] infiltration.
*[[Chemotherapy]] [[drugs]] that may be used with or without [[prednisone]] include:
**[[Chlorambucil]] ([[Leukeran]])
**[[Fludarabine]] ([[Fludara]])
**[[Bendamustine]] ([[Treanda]])
**[[Cyclophosphamide]] ([[Cytoxan]], Procytox)


Complications such as [[hyperviscosity syndrome]], symptomatic sensorimotor peripheral neuropathy, systemic [[amyloidosis]], [[renal insufficiency]], or symptomatic cryoglobulinemia were also suggested as indications for therapy.<ref name="Kyel2003">{{cite journal | author=Kyle RA, Treon SP, Alexanian R, Barlogie B, Bjorkholm M, Dhodapkar M, Lister TA, Merlini G, Morel P, Stone M, Branagan AR, Leblond V | title=Prognostic markers and criteria to initiate therapy in Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia | journal=Semin Oncol | year=2003 | pages=116-20 | volume=30 | issue=2  | id=PMID 12720119}}</ref>
*[[Combination therapy|Combinations]] of [[chemotherapy]] [[drugs]] that may be used include:
**DRC – [[dexamethasone]] ([[Decadron]], [[Dexasone]]), [[rituximab]] ([[Rituxan]]) and [[cyclophosphamide]]
**BRD – [[bortezomib]] ([[Velcade]]) and [[rituximab]], with or without [[dexamethasone]]
**CVP – [[cyclophosphamide]], [[vincristine]] ([[Vincristine|Oncovin]]) and [[prednisone]]
**R-CVP – CVP with [[rituximab]]
**[[Thalidomide]] ([[Thalomid]]) and [[rituximab]]


Treatment includes the monoclonal antibody [[rituximab]], sometimes in combination with chemotherapeutic drugs such as [[chlorambucil]], [[cyclophosphamide]], or [[vincristine]].  [[Corticosteroid]]s may also be used in combination. [[Plasmapheresis]] can be used to treat the hyperviscosity syndrome by removing the paraprotein from the blood, although it does not address the underlying disease.<ref name="Gertz">{{cite journal | author=Gertz MA | title=Waldenstrom macroglobulinemia: a review of therapy | journal=Am J Hematol | year=2005 | pages=147-57 | volume=79 | issue=2  | id=PMID 15929102}}</ref>
{| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
| valign="top" |
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Treatment Regimen<ref name="ADR">Waldenström's macroglobulinemia: prognosis and management. Blood Cancer Journal (2015)http://www.nature.com/bcj/journal/v5/n3/full/bcj201528a.html Accessed on November 13, 2015</ref>
}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Drugs}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Side effects}}
|-
! style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''[[CHOP-R regimen]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Cyclophosphamide]]
*[[Doxorubicin]]
*[[Vincristine]]
*[[Prednisone]]
*[[Rituximab]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Nausea]]
*[[Alopecia]]
*[[Granulocytopenia]]
*[[Cardiotoxicity]]
*[[Mucositis]]
|-
! style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''[[Ibrutinib]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Ibrutinib]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Fatigue]]
*[[Cytopenia]]
*[[Bleeding]]
*[[Atrial fibrillation]]
*[[Opportunistic infection]]
|-
! style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''[[Rituximab]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Rituximab]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Infusion-related reaction|Infusion related reaction]]
*[[Hepatitis B]] [[reaction]]
*Progressive multi-focal leukoencephaloptahy
|-
! style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''FR regimen'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Fludarabine]]
*[[Rituximab]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Neutropenia]] (63%)
*[[Thrombocytopenia]]
*[[Pneumonia]]
|-
! style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''BDR regimen'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Bortezomib]]
*[[Dexamethasone]]
*[[Rituximab]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Peripheral neuropathy]] - [[Reversible cell|reversible]] in 61% of [[patients]]
*[[Infections]]
|-
! style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''DRC regimen'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Dexamethasone]]
*[[Rituximab]]
*[[Cyclophosphamide]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Neutropenia]]
|-
! style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''CR regimen'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Cladribine]]
*[[Rituximab]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Anemia]]
*[[Neurological]] [[symptoms]]
*[[Symptomatic]] [[cryoglobulinemia]]
*[[Thrombocytopenia]]
|-
! style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''IR regimen'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Ibrutinib]]
*[[Rituximab]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Anemia]]
*[[Neurological]] [[symptoms]]
*[[Symptomatic]] [[cryoglobulinemia]]
*[[Thrombocytopenia]]
*[[Atrial fibrillation]]
|}


Recently, [[autologous bone marrow transplantation]] has been added to the available treatment options.<ref name="Yang">{{cite journal | author=Yang L, Wen B, Li H, Yang M, Jin Y, Yang S, Tao J | title=Autologous peripheral blood stem cell transplantation for Waldenstrom's macroglobulinemia | journal=Bone Marrow Transplant | year=1999 | pages=929-30 | volume=24 | issue=8  | id=PMID 10516708}}</ref><ref name="Martino">{{cite journal | author=Martino R, Shah A, Romero P, Brunet S, Sierra J, Domingo-Albos A, Fruchtman S, Isola L | title=Allogeneic bone marrow transplantation for advanced Waldenstrom's macroglobulinemia | journal=Bone Marrow Transplant | year=1999 | pages=747-9 | volume=23 | issue=7 | id=PMID 10218857}}</ref><ref name="Anagnostopoulos">{{cite journal | author=Anagnostopoulos A, Dimopoulos MA, Aleman A, Weber D, Alexanian R, Champlin R, Giralt S | title=High-dose chemotherapy followed by stem cell transplantation in patients with resistant Waldenstrom's macroglobulinemia | journal=Bone Marrow Transplant | year=2001 | pages=1027-9 | volume=27 | issue=10 | id=PMID 11438816}}</ref><ref name="Tournilhac">{{cite journal | author=Tournilhac O, Leblond V, Tabrizi R, Gressin R, Senecal D, Milpied N, Cazin B, Divine M, Dreyfus B, Cahn JY, Pignon B, Desablens B, Perrier JF, Bay JO, Travade P | title=Transplantation in Waldenstrom's macroglobulinemia--the French experience | journal=Semin Oncol | year=2003 | pages=291-6 | volume=30 | issue=2  | id=PMID 12720155}}</ref>
{|
|
[[File:Rituximab therapy gif.gif|thumb|250px|none|Interstitial pneumonitis, post-rituximab therapy in a lymphoplasmacytic lymphoma patient. Helical computed tomographic scanning showed ground-glass shadowing in bilateral lungs before prednisone treatment and a recovery at 1 week post-treatment.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC4352371_ccr30003-0133-f1&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=61 Source: Bai X. et al, Department of Hematology, Beijing Tiantan Hospital, Capital Medical University 6 Tiantan Xili Dongcheng District, Beijing, 100050, China.]]]
|}
 
====Hyperviscosity syndrome:====
*[[Lymphoplasmacytic lymphoma|Waldenstrom's macroglobulinemia]] [[Complication (medicine)|complicated]] with [[hyperviscosity syndrome]] is a [[medical emergency]] and requires [[prompt]] [[Treatments|treatment]] with [[plasmapheresis]].<ref name="ADR">Waldenström's macroglobulinemia: prognosis and management. Blood Cancer Journal (2015)http://www.nature.com/bcj/journal/v5/n3/full/bcj201528a.html Accessed on November 13, 2015</ref>
*[[Plasmapheresis]] temporarily lowers [[IgM]] levels by removing some of the [[abnormal]] [[IgM]] from the [[blood]], which makes [[blood]] thinner.
*[[Plasmapheresis]] is usually given until [[chemotherapy]] [[Starter (fermentation)|starts]] to [[Work (thermodynamics)|work]].
*[[Plasmapheresis]] is [[Combination therapy|combined]] with [[chemotherapy]] to [[control]] the [[disease]] for a longer [[period]] of [[Time-series|time]].
*[[Plasmapheresis]] is also used in WM [[patients]] with [[hemolysis]].
 
===Initial treatment of Waldenstrom's macroglobulinemia:===
{{familytree/start}}
{{familytree |boxstyle=text-align: left;| | | | | | A01 | | | | | |A01= Does the [[patient]] has an [[indication]] for LPL treatment?
*[[B symptoms]] (recurrent [[fever]], [[night sweats]], [[weight loss]], [[fatigue]])
*[[Hyperviscosity]]
*Bulky/[[symptomatic]] [[lymphadenopathy]]
*[[Symptomatic]] [[hepatosplenomegaly]]
*[[Symptomatic]] [[organomegaly]] or [[organ]]/[[tissue]] [[infiltration]]
*WM associated [[peripheral neuropathy]]
*[[Cold agglutinin hemolytic anemia]]
*[[Symptomatic]] [[cryoglobulinemia]]
*[[Immune hemolytic anemia]] and/or [[thrombocytopenia]]
*LPL associated [[AL amyloidosis]]
*LPL associated [[nephropathy]]
*[[Hemoglobin]] = or < 10g/dl
*[[Platelet]] count = or < 100 x 10'9/L}}
{{familytree | | | |,|-|-|^|-|-|.| | | }}
{{familytree | | | B01 | | | | B02 | | |B01=Yes|B02=No}}
{{familytree | | | |!| | | | | |!| }}
{{familytree | | | C01 | | | | |!| |C01=Does the patient has [[symptoms]] associated with [[hyperviscosity]] such as: [[Oronasal]] [[bleeding]], [[blurred vision]], [[headaches]], [[dizziness]], [[paresthesias]], [[retinal vein engorgement]], [[flame-shaped hemorrhages]], [[papilledema]], [[stupor]] or [[coma]].|C02=asymptomatic/smoldering WM: Follow every 4-6 months with CBC and monoclonal protein levels}}
{{familytree | | |,|-|^|.| | | |!| }}
{{familytree | D01 | | D02 | |D03|D01=No|D02=Yes|D03=For smoldering/[[asymptomatic]] WM/LPL, just follow up every 4-6 months with [[CBC]] and [[monoclonal protein]] levels}}
{{familytree | |!| | | |!| | | | | | | | | }}
{{familytree | E01 | | E02 |.| | | | | | |E01=Assess degree of [[symptom]] burden in WM/LPL [[pateint]]|E02=Consider emergent [[plasmapheresis]] for treatment of [[hyperviscosity]]}}
{{Familytree |,|^|-|-|-|.| |!| | | }}
{{familytree | F01 | | F02 |!| | | | | | |F01=Low|F02=Moderate/High}}
{{Familytree | |!| | | |!| |!| | | | | | | }}
{{familytree | G01 | | G02 |'| | | |G01=Following are the 2 options for [[patients]] with low [[tumor]] burden with minimal [[symptoms]]:
*Single agent [[Rituximab]]
*[[Rituximab]] + [[chemotherapy]] as with high burden [[disease]]|G02=Following 2 are the preferred [[regimens]] for [[moderate]]/[[severe]] [[symptoms]] or high [[tumor]] burden:
*[[Bendamustine]] + [[rituximab]]
*[[Dexamethasone]] & [[rituximab]] + [[cyclophosphamide]]}}
{{familytree/end}}
 
===Drug of choice for Bing-Neel Syndrome===
* Many [[Recent changes|recent]] [[Study design|studies]] have shown to be [[Ibrutinib]] (560mg), an [[oral]] [[Bruton's tyrosine kinase]] [[tyrosine kinase inhibitor|inhibitor]], with or without [[Concurrent overlap|concurrent]] [[Rituximab]], as a [[drug]] of choice for the [[Treatments|treatment]] of [[Bing-Neel syndrome]]. It [[Work function|works]] by [[Penetrance|penetrating]] the [[blood brain barrier]].<ref name="pmid30228918">{{cite journal| author=O'Neil DS, Francescone MA, Khan K, Bachir A, O'Connor OA, Sawas A| title=A Case of Bing-Neel Syndrome Successfully Treated with Ibrutinib. | journal=Case Rep Hematol | year= 2018 | volume= 2018 | issue=  | pages= 8573105 | pmid=30228918 | doi=10.1155/2018/8573105 | pmc=6136466 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30228918  }} </ref><ref name="pmid27758817">{{cite journal| author=Minnema MC, Kimby E, D'Sa S, Fornecker LM, Poulain S, Snijders TJ et al.| title=Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome. | journal=Haematologica | year= 2017 | volume= 102 | issue= 1 | pages= 43-51 | pmid=27758817 | doi=10.3324/haematol.2016.147728 | pmc=5210231 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27758817  }} </ref><ref name="pmid30279255">{{cite journal| author=Tallant A, Selig D, Wanko SO, Roswarski J| title=First-line ibrutinib for Bing-Neel syndrome. | journal=BMJ Case Rep | year= 2018 | volume= 2018 | issue=  | pages=  | pmid=30279255 | doi=10.1136/bcr-2018-226102 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30279255  }} </ref><ref name="pmid26689870">{{cite journal| author=Cabannes-Hamy A, Lemal R, Goldwirt L, Poulain S, Amorim S, Pérignon R et al.| title=Efficacy of ibrutinib in the treatment of Bing-Neel syndrome. | journal=Am J Hematol | year= 2016 | volume= 91 | issue= 3 | pages= E17-9 | pmid=26689870 | doi=10.1002/ajh.24279 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26689870  }} </ref><ref name="pmid27409073">{{cite journal| author=Mason C, Savona S, Rini JN, Castillo JJ, Xu L, Hunter ZR et al.| title=Ibrutinib penetrates the blood brain barrier and shows efficacy in the therapy of Bing Neel syndrome. | journal=Br J Haematol | year= 2017 | volume= 179 | issue= 2 | pages= 339-341 | pmid=27409073 | doi=10.1111/bjh.14218 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27409073  }} </ref>
 
* One or more of the following [[treatments]] can be given for [[lymphoplasmacytic lymphoma|Waldenstrom's macroglobulinemia]].
 
=====Targeted therapy=====
*[[Targeted therapy]] uses [[drugs]] to [[Targeted therapy|target]] [[Specific activity|specific]] [[molecules]] (such as [[proteins]]) on the [[Surface anatomy|surface]] of [[cancer cells]]. These [[molecules]] help send [[Signals (biology)|signals]] that tell [[Cells (biology)|cells]] to [[Growth|grow]] or divide. By [[Targeted therapy|targeting]] these [[molecules]], the [[drugs]] stop the [[growth]] and [[Spread of the cancer|spread of cancer]] [[cancer cells|cells]] while [[Limiting factor|limiting]] harm to [[normal]] [[cells]].
*[[Targeted therapy]] [[drugs]] used alone or in [[Combination therapy|combination]] to [[Treatments|treat]] [[lymphoplasmacytic lymphoma|Waldenstrom's macroglobulinemia]] include [[rituximab]], [[bortezomib]] and [[ibrutinib]] (Imbruvica).
 
=====Immunotherapy=====
*[[Immunotherapy]] works by [[Stimulant|stimulating]], [[boosting]], [[Restoration device|restoring]] or [[Acting out|acting]] like the [[Body|body’s]] [[immune system]] to create a [[Response element|response]] against [[cancer cells]]. [[Immunomodulatory]] [[drugs]] are a type of [[immunotherapy]] that [[Interference|interferes]] with the [[growth]] and [[Division (biology)|division]] of [[cancer cells]].
*[[Thalidomide]] is a type of [[immunomodulatory]] [[drug]] that may be used to [[Treatments|treat]] [[lymphoplasmacytic lymphoma|Waldenstrom's macroglobulinemia]].
 
=====Radiation therapy=====
In some [[rare]] [[Case-based reasoning|cases]], [[external beam radiation therapy]] may be required to [[Treatments|treat]] WM that [[Development|develops]] outside of the [[lymphatic system]] (called extralymphatic [[disease]]).


==References==
==References==
{{reflist|2}}
{{Reflist|2}}


{{WH}}
{{WH}}
{{WS}}
{{WS}}
[[Category:Disease]]
[[Category:Disease]]
[[Category:Blood]]
[[Category:Blood]]
[[Category:Hematology]]
[[Category:Hematology]]

Latest revision as of 19:00, 15 August 2019

Waldenström's macroglobulinemia Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Waldenström's macroglobulinemia 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

Bone Marrow Aspiration and Biopsy

Electrophoresis and Immunofixation

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

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

Waldenström's macroglobulinemia medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Waldenström's macroglobulinemia 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 Waldenström's macroglobulinemia medical therapy

CDC on Waldenström's macroglobulinemia medical therapy

Waldenström's macroglobulinemia medical therapy in the news

Blogs on Waldenström's macroglobulinemia medical therapy

Directions to Hospitals Treating Waldenström's macroglobulinemia

Risk calculators and risk factors for Waldenström's macroglobulinemia medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2], Mirdula Sharma, MBBS [3], Roukoz A. Karam, M.D.[4]; Grammar Reviewer: Natalie Harpenau, B.S.[5]

Overview

Risk stratification determines the protocol of management used for Waldenstrom's macroglobulinemia. There is no treatment for asymptomatic Waldenstrom's macroglobulinemia. The mainstay of treatment for symptomatic Waldenstrom's macroglobulinemia is Rituximab +/- Chemotherapy. Hyperviscosity syndrome is a medical emergency and requires prompt treatment with plasmapheresis. Drug of choice for the treatment of bing-neel syndrome is Ibrutinib with or without concurrent rituximab. Other treatment options include targeted therapy, immunotherapy and radiation therapy.

Medical Therapy

There's no cure for WM with current therapies. Instead, the treatment goals are to control symptoms and prevent end-organ damage, while maximizing quality of life. There is no standard therapy for the treatment of WM. While various drugs and combinations have demonstrated to have provided clinical benefit, hence, there are several different options for treating Waldenstrom's macroglobulinemia depending on stage of the disease:[1]

Summary of how to approach different patients with Waldenstrom's macroglobulinemia
Patient's condition/parameters How to proceed accordingly
Observation
Hperviscosity present:

Hyperviscosity absent:

  • DRC only
Consider clinical trial + stem cell transplant in selected patients:

Watchful waiting/active surveillance for asymptomatic patients with WM

There is no treatment for asymptomatic patients with WM. As WM develops slowly and may not need to be treated right away, it is monitored by healthcare team every 3-6 months which is known as watchful waiting/active surveillance and treatment is started when symptoms appear, such as hyperviscosity syndrome, or there are signs that the disease is progressing more quickly.[2] Active surveillance includes monitoring of the following laboratory parameters:

Symptomatic patients with WM

Symptomatic patients with WM are started on chemotherapy depending on the stage.[3]

Treatment Regimen[3]

Drugs Side effects

CHOP-R regimen

Ibrutinib

Rituximab

FR regimen

BDR regimen

DRC regimen

CR regimen

IR regimen

Interstitial pneumonitis, post-rituximab therapy in a lymphoplasmacytic lymphoma patient. Helical computed tomographic scanning showed ground-glass shadowing in bilateral lungs before prednisone treatment and a recovery at 1 week post-treatment.Source: Bai X. et al, Department of Hematology, Beijing Tiantan Hospital, Capital Medical University 6 Tiantan Xili Dongcheng District, Beijing, 100050, China.

Hyperviscosity syndrome:

Initial treatment of Waldenstrom's macroglobulinemia:

 
 
 
 
 
Does the patient has an indication for LPL treatment?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient has symptoms associated with hyperviscosity such as: Oronasal bleeding, blurred vision, headaches, dizziness, paresthesias, retinal vein engorgement, flame-shaped hemorrhages, papilledema, stupor or coma.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
Yes
 
For smoldering/asymptomatic WM/LPL, just follow up every 4-6 months with CBC and monoclonal protein levels
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assess degree of symptom burden in WM/LPL pateint
 
Consider emergent plasmapheresis for treatment of hyperviscosity
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low
 
Moderate/High
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Following are the 2 options for patients with low tumor burden with minimal symptoms:
 
Following 2 are the preferred regimens for moderate/severe symptoms or high tumor burden:
  • Bendamustine + rituximab
  • Dexamethasone & rituximab + cyclophosphamide
    •  
     
     
     
     
     

    Drug of choice for Bing-Neel Syndrome

    Targeted therapy
    Immunotherapy
    Radiation therapy

    In some rare cases, external beam radiation therapy may be required to treat WM that develops outside of the lymphatic system (called extralymphatic disease).

    References

    1. ↑ Lymphoplasmacytic lymphoma. Canadian Cancer Society 2015. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/lymphoplasmacytic-lymphoma/?region=ab Accessed on November 6 2015
    2. ↑ Waldenström's macroglobulinemia. Patient (2015)http://patient.info/doctor/waldenstroms-macroglobulinaemia-pro Accessed on November 10, 2015
    3. ↑ 3.0 3.1 3.2 Waldenström's macroglobulinemia: prognosis and management. Blood Cancer Journal (2015)http://www.nature.com/bcj/journal/v5/n3/full/bcj201528a.html Accessed on November 13, 2015
    4. ↑ O'Neil DS, Francescone MA, Khan K, Bachir A, O'Connor OA, Sawas A (2018). "A Case of Bing-Neel Syndrome Successfully Treated with Ibrutinib". Case Rep Hematol. 2018: 8573105. doi:10.1155/2018/8573105. PMC 6136466. PMID 30228918.
    5. ↑ Minnema MC, Kimby E, D'Sa S, Fornecker LM, Poulain S, Snijders TJ; et al. (2017). "Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome". Haematologica. 102 (1): 43–51. doi:10.3324/haematol.2016.147728. PMC 5210231. PMID 27758817.
    6. ↑ Tallant A, Selig D, Wanko SO, Roswarski J (2018). "First-line ibrutinib for Bing-Neel syndrome". BMJ Case Rep. 2018. doi:10.1136/bcr-2018-226102. PMID 30279255.
    7. ↑ Cabannes-Hamy A, Lemal R, Goldwirt L, Poulain S, Amorim S, Pérignon R; et al. (2016). "Efficacy of ibrutinib in the treatment of Bing-Neel syndrome". Am J Hematol. 91 (3): E17–9. doi:10.1002/ajh.24279. PMID 26689870.
    8. ↑ Mason C, Savona S, Rini JN, Castillo JJ, Xu L, Hunter ZR; et al. (2017). "Ibrutinib penetrates the blood brain barrier and shows efficacy in the therapy of Bing Neel syndrome". Br J Haematol. 179 (2): 339–341. doi:10.1111/bjh.14218. PMID 27409073.

    Template:WH Template:WS

    Retrieved from "https://www.wikidoc.org/index.php?title=Waldenström%27s_macroglobulinemia_medical_therapy&oldid=1579747"