Waldenström's macroglobulinemia medical therapy: Difference between revisions

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__NOTOC__
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{{Waldenström's macroglobulinemia}}
{{Waldenström's macroglobulinemia}}
{{CMG}}{{AE}}{{MGS}}
{{CMG}}; {{AE}} {{S.M.}}, {{MGS}}, {{RAK}}; {{GRR}} {{Nat}}
==Overview==
==Overview==
Risk stratification determines the protocol of management used for Waldenström's macroglobulinemia patients. Watchful waiting is recommended for asymptomatic Waldenström's macroglobulinemia. Symptomatic Waldenström's macroglobulinemia is treated with [[Rituximab]] +/- [[Chemotherapy]].<ref name="PHARM">Waldenström's macroglobulinemia. Medscape (2015)http://emedicine.medscape.com/article/2057687-overview Accessed on November 11, 2015</ref>
[[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 are several different options for Waldenström Macroglobulinemia.<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>
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]]


==Asymptomatic/Smoldering Waldenström's macroglobulinemia==
====Symptomatic patients with WM====
Patients who do not have symptoms and whose cancer does not seem to be progressing often do not need treatment.
[[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>
They can be monitored every 3-6 months - a 'wait and watch approach'.<ref name="BM">Waldenström's macroglobulinemia. Patient (2015)http://patient.info/doctor/waldenstroms-macroglobulinaemia-pro Accessed on November 10, 2015</ref>


==Symptomatic Waldenström's macroglobulinemia==
*Initial [[Staging (pathology)|stage]] of WM is [[Association (statistics)|associated]] with:
Symptomatic patients with Waldenström Macroglobulinemia are started on chemotherapy depending on the stage.<ref name="PHARM">Waldenström's macroglobulinemia. Medscape (2015)http://emedicine.medscape.com/article/2057687-overview Accessed on November 11, 2015</ref>


===Initial stage of Waldenström's macroglobulinemia associated with===
:*[[Neuropathy]]
*Neuropathy,
:*[[Anemia]] or [[cytopenias]]
*Anemia or cytopenias,
:*Low-[[volume]] [[Nodal (protein)|nodal]] involvement
*Low-volume nodal involvement, and
:*[[Asymptomatic]] [[splenomegaly]]
*Asymptomatic splenomegaly
'''Treatment:''' Single-agent Rituximab therapy


===Late stage of Waldenström's macroglobulinemia associated with===
*Late [[Staging (pathology)|stage]] of WM is [[Association (statistics)|associated]] with:
*Adenopathy,
:*[[Adenopathy]]
*Symptomatic splenomegaly,
:*[[Symptomatic]] [[splenomegaly]]
*Cytopenias,
:*[[Cytopenia|Cytopenias]]
*Hyperviscosity syndrome,
:*[[Hyperviscosity syndrome]]
*Neuropathy, or
:*[[Neuropathy]]
*Constitutional symptoms
:*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]].


'''Treatment regimen used:'''<ref name="PHARM">Waldenström's macroglobulinemia. Medscape (2015)http://emedicine.medscape.com/article/2057687-overview Accessed on November 11, 2015</ref><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>
*[[Chemotherapy]] [[drugs]] that may be used with or without [[prednisone]] include:  
**[[Chlorambucil]] ([[Leukeran]])
**[[Fludarabine]] ([[Fludara]])
**[[Bendamustine]] ([[Treanda]])
**[[Cyclophosphamide]] ([[Cytoxan]], Procytox)


'''CHOP-R regimen:'''
*[[Combination therapy|Combinations]] of [[chemotherapy]] [[drugs]] that may be used include:
*Cyclophosphamide 750 mg/m2 IV day 1;
**DRC – [[dexamethasone]] ([[Decadron]], [[Dexasone]]), [[rituximab]] ([[Rituxan]]) and [[cyclophosphamide]]
*Doxorubicin 50 mg/m2;
**BRD – [[bortezomib]] ([[Velcade]]) and [[rituximab]], with or without [[dexamethasone]]
*Vincristine 1.4 mg/m2 IV (max 2 mg) day 1;
**CVP – [[cyclophosphamide]], [[vincristine]] ([[Vincristine|Oncovin]]) and [[prednisone]]
*Prednisone 50 mg/m2 PO days 1-5;
**R-CVP – CVP with [[rituximab]]
*Rituximab 375 mg/m2 IV day 1;
**[[Thalidomide]] ([[Thalomid]]) and [[rituximab]]
*Primary: Repeat 21 day cycle for 6-8 cycles
::*'''Adverse Effect:'''
:::*Nausea
:::*Alopecia
:::*Granulocytopenia


'''Ibrutinib''' 420 mg PO once daily until disease progression
{| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
::*'''Adverse Effect:'''
| valign="top" |
:::*Fatigue
|+
:::*Cytopenia
! 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]]
|}


'''Rituximab''' 375 mg/m2 IV once weekly x 4 weeks
{|
::*'''Adverse Effect:'''
|
:::*Infusion related reaction
[[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.]]]
:::*Infections
|}


'''Fludarabine/Rituximab regimen:'''
====Hyperviscosity syndrome:====
*Fludarabine 25 mg/m2 IV days 1-5;
*[[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>
*Rituximab 375 mg/m2 IV day 1;
*[[Plasmapheresis]] temporarily lowers [[IgM]] levels by removing some of the [[abnormal]] [[IgM]] from the [[blood]], which makes [[blood]] thinner.
*Repeat 28 day cycle for 4-6 cycles
*[[Plasmapheresis]] is usually given until [[chemotherapy]] [[Starter (fermentation)|starts]] to [[Work (thermodynamics)|work]].
::*'''Adverse Effect:'''
*[[Plasmapheresis]] is [[Combination therapy|combined]] with [[chemotherapy]] to [[control]] the [[disease]] for a longer [[period]] of [[Time-series|time]].
:::*Neutropenia (63%)
*[[Plasmapheresis]] is also used in WM [[patients]] with [[hemolysis]].
:::*Thrombocytopenia
:::*Pneumonia


'''FCR regimen:'''
===Initial treatment of Waldenstrom's macroglobulinemia:===
*Fludarabine 25 mg/m2 IV days 1-3
{{familytree/start}}
*Cyclophosphamide 250 mg/m2 IV days 1-3
{{familytree |boxstyle=text-align: left;| | | | | | A01 | | | | | |A01= Does the [[patient]] has an [[indication]] for LPL treatment?
*Rituximab 375 mg/m2 IV day 1
*[[B symptoms]] (recurrent [[fever]], [[night sweats]], [[weight loss]], [[fatigue]])
*Primary: Repeat 28 day cycle for 4-6 cycles
*[[Hyperviscosity]]
*May also be given with mitoxantrone 10 mg/m2 on day 1
*Bulky/[[symptomatic]] [[lymphadenopathy]]
::*'''Adverse Effect:'''
*[[Symptomatic]] [[hepatosplenomegaly]]
:::*Neurtropenia
*[[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}}


'''BR regimen:'''
===Drug of choice for Bing-Neel Syndrome===
*Bendamustine 90 mg/m2 IV days 1-2
* 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>
*Rituximab 375 mg/m2 IV day 1
*Primary: Repeat 21 day cycle for 6 cycles
::*'''Adverse Effect:'''
:::*Myelosupression
:::*Neutropenia
:::*Thrombocytopenia


'''BDR regimen:'''
* One or more of the following [[treatments]] can be given for [[lymphoplasmacytic lymphoma|Waldenstrom's macroglobulinemia]].
*Bortezomib 1.3 mg/m2plus
*Dexamethasone 40 mg IV days 1, 4, 8, and 11
*Rituximab 375 mg/m2 IV day 11
*Primary: Repeat 21 day cycle for 4 cycles
::*'''Adverse Effect:'''
:::*Peripheral neuropathy - reversible in 61% of patients


'''DRC regimen:'''
=====Targeted therapy=====
*Dexamethasone 20 mg IV day 1
*[[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]].
*Rituximab 375 mg/m2 IV day 1
*[[Targeted therapy]] [[drugs]] used alone or in [[Combination therapy|combination]] to [[Treatments|treat]] [[lymphoplasmacytic lymphoma|Waldenstrom's macroglobulinemia]] include [[rituximab]], [[bortezomib]] and [[ibrutinib]] (Imbruvica).
*Cyclophosphamide 100 mg/m2 PO BID days 1-5
*Primary: Repeat 21 day cycle for 6 cycles
::*'''Adverse Effect:'''
:::*Neutropenia
:::*Rituximab associated toxicity


'''CR regimen:'''
=====Immunotherapy=====
*Cladribine 0.1 mg/kg SC days 1-5
*[[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]].
*Rituximab 375 mg/m2 IV day 1
*[[Thalidomide]] is a type of [[immunomodulatory]] [[drug]] that may be used to [[Treatments|treat]] [[lymphoplasmacytic lymphoma|Waldenstrom's macroglobulinemia]].
*Primary: Repeat 28 day cycle for 4 cycles
::*'''Adverse Effect:'''
:::*Anemia
:::*Neurological symptoms
:::*symptomatic cryoglobulinemia
:::*Thrombocytopenia


===Hyperviscosity syndrome===
=====Radiation therapy=====
*Plasmapheresis is recommended emergent treatment option for patients with Waldenström Macroglobulinemia who develop hyperviscosity symptoms.<ref name="PHARM">Waldenström's macroglobulinemia. Medscape (2015)http://emedicine.medscape.com/article/2057687-overview Accessed on November 11, 2015</ref>
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]]).
*Plasmapheresis temporarily lowers IgM levels by removing some of the abnormal IgM from the blood, which makes the blood thinner.
*However, plasmapheresis does not affect the lymphoma cells.
*Plasmapheresis is usually given until chemotherapy starts to work.
*Plasmapheresis is combined with chemotherapy to control the disease for a longer period of time.


==Salvage approach==
*Stem cell transplant is used in patients whose lymphoma relapses or is not responding to other treatments (refractory). <ref name="PHARM">Waldenström's macroglobulinemia. Medscape (2015)http://emedicine.medscape.com/article/2057687-overview Accessed on November 11, 2015</ref>
==References==
==References==
{{reflist|2}}
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Latest revision as of 19:00, 15 August 2019

Waldenström's macroglobulinemia Microchapters

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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.

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