Lymphoplasmacytic lymphoma medical therapy: Difference between revisions

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There's no [[cure]] for WM/LPL 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 LPL. While various [[drugs]] and combinations have demonstrated to have provided [[clinical]] benefit, hence, there are several different options for treating [[lymphoplasmacytic lymphoma]] depending on 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>
There's no [[cure]] for WM/LPL 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 LPL. While various [[drugs]] and combinations have demonstrated to have provided [[clinical]] benefit, hence, there are several different options for treating [[lymphoplasmacytic lymphoma]] depending on 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>


====Watchful waiting/active surveillance for asymptomatic patients with LPL:====
====Watchful waiting/active surveillance for asymptomatic patients with LPL====
There is no treatment for [[asymptomatic]] patients with LPL. As LPL develops slowly and may not need to be treated right away, it is monitored by [[Health care|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.<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 of the following laboratory parameters:
There is no treatment for [[asymptomatic]] patients with LPL. As LPL develops slowly and may not need to be treated right away, it is monitored by [[Health care|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.<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 of the following laboratory parameters:
*[[Complete blood count]] ([[Complete blood count|CBC]]) with differential.
*[[Complete blood count]] ([[Complete blood count|CBC]]) with differential
*Complete metabolic panel ([[CMP-N-acetylneuraminate monooxygenase|CMP]]).
*Complete metabolic panel ([[CMP-N-acetylneuraminate monooxygenase|CMP]])
*[[Immunoglobulin]] levels in the [[serum]] (quantitative).
*[[Immunoglobulin]] levels in the [[serum]] (quantitative)
*[[Serum protein electrophoresis]].
*[[Serum protein electrophoresis]]


====Symptomatic patients with LPL:====
====Symptomatic patients with LPL====
[[Symptomatic]] patients with LPL are started on [[chemotherapy]] depending on the 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>
[[Symptomatic]] patients with LPL are started on [[chemotherapy]] depending on the 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 stage of LPL is associated with:
*Initial stage of LPL is associated with:
:*[[Neuropathy]].
:*[[Neuropathy]]
:*[[Anemia]] or [[cytopenias]].
:*[[Anemia]] or [[cytopenias]]
:*Low-volume nodal involvement.
:*Low-volume nodal involvement  
:*[[Asymptomatic]] [[splenomegaly]].
:*[[Asymptomatic]] [[splenomegaly]]


*Late stage of LPL is associated with:
*Late stage of LPL is associated with:
:*[[Adenopathy]].
:*[[Adenopathy]]
:*[[Symptomatic]] [[splenomegaly]].
:*[[Symptomatic]] [[splenomegaly]]  
:*[[Cytopenia|Cytopenias]].
:*[[Cytopenia|Cytopenias]]
:*[[Hyperviscosity syndrome]].
:*[[Hyperviscosity syndrome]]
:*[[Neuropathy]].
:*[[Neuropathy]]
:*Constitutional [[symptoms]].
:*Constitutional [[symptoms]]
*[[Men]] and women with childbearing potential should receive [[counseling]] about the potential effect of treatment on their [[fertility]] and options for [[fertility]]-preserving measures.
*[[Men]] and women with childbearing potential should receive [[counseling]] about the potential effect of treatment on their [[fertility]] and options for [[fertility]]-preserving measures.
*[[Chemotherapy]] [[drugs]] that may be used with or without [[prednisone]] include:  
*[[Chemotherapy]] [[drugs]] that may be used with or without [[prednisone]] include:  
**[[Chlorambucil]] ([[Leukeran]]).
**[[Chlorambucil]] ([[Leukeran]])
**[[Fludarabine]] ([[Fludara]]).
**[[Fludarabine]] ([[Fludara]])
**[[Bendamustine]] ([[Treanda]]).
**[[Bendamustine]] ([[Treanda]])
**[[Cyclophosphamide]] ([[Cytoxan]], Procytox).
**[[Cyclophosphamide]] ([[Cytoxan]], Procytox)


*Combinations of [[chemotherapy]] [[drugs]] that may be used include:
*Combinations of [[chemotherapy]] [[drugs]] that may be used include:
**DRC – [[dexamethasone]] ([[Decadron]], [[Dexasone]]), [[rituximab]] ([[Rituxan]]) and [[cyclophosphamide]].
**DRC – [[dexamethasone]] ([[Decadron]], [[Dexasone]]), [[rituximab]] ([[Rituxan]]) and [[cyclophosphamide]]
**BRD – [[bortezomib]] ([[Velcade]]) and [[rituximab]], with or without [[dexamethasone]].
**BRD – [[bortezomib]] ([[Velcade]]) and [[rituximab]], with or without [[dexamethasone]]
**CVP – [[cyclophosphamide]], [[vincristine]] (Oncovin) and [[prednisone]].
**CVP – [[cyclophosphamide]], [[vincristine]] (Oncovin) and [[prednisone]]
**R-CVP – CVP with [[rituximab]].
**R-CVP – CVP with [[rituximab]]
**[[Thalidomide]] ([[Thalomid]]) and [[rituximab]].
**[[Thalidomide]] ([[Thalomid]]) and [[rituximab]]


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===Drug of choice for Bing-Neel Syndrome:===
===Drug of choice for Bing-Neel Syndrome===
* Many recent studies have shown to be [[Ibrutinib]] (560mg), an oral Bruton's [[tyrosine kinase inhibitor]], with or without concurrent [[Rituximab]], as a [[drug]] of choice for treatment of [[Bing-Neel syndrome]]. It works by 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>
* Many recent studies have shown to be [[Ibrutinib]] (560mg), an oral Bruton's [[tyrosine kinase inhibitor]], with or without concurrent [[Rituximab]], as a [[drug]] of choice for treatment of [[Bing-Neel syndrome]]. It works by 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]].
* One or more of the following treatments can be given for [[lymphoplasmacytic lymphoma]].


=====Targeted therapy:=====
=====Targeted therapy=====
*[[Targeted therapy]] uses [[drugs]] to target specific [[molecules]] (such as [[proteins]]) on the surface of [[cancer cells]]. These [[molecules]] help send signals that tell cells to grow or divide. By targeting these [[molecules]], the [[drugs]] stop the [[growth]] and spread of [[cancer cells]] while limiting harm to normal [[cells]].  
*[[Targeted therapy]] uses [[drugs]] to target specific [[molecules]] (such as [[proteins]]) on the surface of [[cancer cells]]. These [[molecules]] help send signals that tell cells to grow or divide. By targeting these [[molecules]], the [[drugs]] stop the [[growth]] and spread of [[cancer cells]] while limiting harm to normal [[cells]].  
*[[Targeted therapy]] [[drugs]] used alone or in combination to treat [[lymphoplasmacytic lymphoma]] include [[rituximab]], [[bortezomib]] and [[ibrutinib]] (Imbruvica).
*[[Targeted therapy]] [[drugs]] used alone or in combination to treat [[lymphoplasmacytic lymphoma]] include [[rituximab]], [[bortezomib]] and [[ibrutinib]] (Imbruvica).


=====Immunotherapy:=====
=====Immunotherapy=====
*[[Immunotherapy]] works by stimulating, [[boosting]], restoring or acting like the body’s [[immune system]] to create a response against [[cancer cells]]. [[Immunomodulatory]] [[drugs]] are a type of [[immunotherapy]] that interferes with the [[growth]] and [[Division (biology)|division]] of [[cancer cells]].
*[[Immunotherapy]] works by stimulating, [[boosting]], restoring or acting like the body’s [[immune system]] to create a response against [[cancer cells]]. [[Immunomodulatory]] [[drugs]] are a type of [[immunotherapy]] that interferes with the [[growth]] and [[Division (biology)|division]] of [[cancer cells]].
*[[Thalidomide]] is a type of [[immunomodulatory]] [[drug]] that may be used to treat [[lymphoplasmacytic lymphoma]].
*[[Thalidomide]] is a type of [[immunomodulatory]] [[drug]] that may be used to treat [[lymphoplasmacytic lymphoma]].


=====Radiation therapy:=====
=====Radiation therapy=====
In some rare cases, [[external beam radiation therapy]] may be required to treat LPL that develops outside of the [[lymphatic system]] (called extralymphatic [[disease]]).
In some rare cases, [[external beam radiation therapy]] may be required to treat LPL that develops outside of the [[lymphatic system]] (called extralymphatic [[disease]]).



Revision as of 16:35, 21 February 2019

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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]

Overview

Risk stratification determines the protocol of management used for lymphoplasmacytic lymphoma. There is no treatment for asymptomatic lymphoplasmacytic lymphoma. The mainstay of treatment for symptomatic lymphoplasmacytic lymphoma is Rituximab +/- Chemotherapy. Hyperviscosity syndrome is a medical emergency and requires prompt treatment with plasmapheresis.

Medical Therapy

There's no cure for WM/LPL 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 LPL. While various drugs and combinations have demonstrated to have provided clinical benefit, hence, there are several different options for treating lymphoplasmacytic lymphoma depending on stage of the disease:[1]

Watchful waiting/active surveillance for asymptomatic patients with LPL

There is no treatment for asymptomatic patients with LPL. As LPL 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 LPL

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

  • Initial stage of LPL is associated with:
  • Late stage of LPL is associated with:
Treatment Regimen[3]

Drugs Side effects

CHOP-R regimen

Ibrutinib

Rituximab

FR regimen

BDR regimen

DRC regimen

CR regimen

IR regimen

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 Lymphoplasmacytic lymphoma:

 
 
 
 
 
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 LPL 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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