Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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{| class="wikitable" style="text-align:center; width:50%;"
 
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!colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26"|'''Section editor'''
 
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|-
 
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|style="background-color:#F0F0F0"|[[File:Sanjay_mohan.png|frameless|upright=0.3|center]]
 
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|<big>[[User:Sanjaymohan|Sanjay R. Mohan, MD, MSCI]]<br>Vanderbilt University<br>Nashville, TN</big>
 
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|-
 
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|}
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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|}
 
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{{TOC limit|limit=3}}
 
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=Guidelines=
 
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==ELN==
 
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*'''2011:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979120/ Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet]
 
−
==ESMO==
 
−
*'''2015:''' Vannucchi et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Philadelphia-Chromosome-Negative-Chronic-Myeloproliferative-Neoplasms Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
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=="How I Treat"==
 
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*'''2014:''' Vannucchi AM. How I treat polycythemia vera. Blood. 2014 Nov 20;124(22):3212-20. Epub 2014 Oct 2. [http://www.bloodjournal.org/content/124/22/3212.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25278584 PubMed]
 
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==[https://www.nccn.org/ NCCN]==
 
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*[https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf NCCN Guidelines - Myeloproliferative Neoplasms]
 
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=First-line therapy=
 
−
==Aspirin monotherapy {{#subobject:5c9446|Regimen=1}}==
 
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<div class="toccolours" style="background-color:#eeeeee">
 
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===Regimen {{#subobject:3983e0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa035572 Landolfi et al. 2004 (ECLAP)]
 
−
|1998-2000
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Placebo|Placebo]]
 
−
| style="background-color:#91cf60" |Seems to have superior combined outcome
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Anticoagulation====
 
−
*[[Aspirin]] 100 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''ECLAP:''' Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. [https://doi.org/10.1056/nejmoa035572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14711910 PubMed]
 
−
==Hydroxyurea monotherapy {{#subobject:511984|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:84f020|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/90/9/3370.long Najean et al. 1997 (FPSG)]
 
−
|1980-NR
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#Pipobroman_monotherapy_88|Pipobroman]]
 
−
|style="background-color:#1a9850"|Superior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa1208500 Marchioli et al. 2012 (CYTO-PV)]
 
−
|2008-2012
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[#Hydroxyurea_monotherapy|Hydroxyurea]]; less strict hematocrit goal
 
−
|style="background-color:#1a9850"|Superior primary endpont
 
−
|-
 
−
|[https://doi.org/10.1182/blood.2021012743 Mascarenhas et al. 2022 (MPD-RC 112)]
 
−
|2011-2016
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Pegintereron_alfa-2a_monotherapy_99|Peginterferon alfa-2a]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CHR rate
 
−
|-
 
−
|[https://doi.org/10.1016/s2352-3026(19)30236-4 Gisslinger et al. 2020 (PROUD-PV)]
 
−
|2013-2015
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Ropeginterferon_alfa-2b_monotherapy_77|Ropeginterferon alfa-2b]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior composite endpoint
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for FPSG is based on the 2011 update.''<br>
 
−
''The following is the approach recommended by Vannucchi in How I Treat (2014).''
 
−
====Chemotherapy====
 
−
*[[Hydroxyurea (Hydrea)]] 500 mg PO twice per day, with titration based on the target hematocrit and hematologic toxicity
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 81 to 100 mg PO once per day, depending on the study
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''FPSG:''' Najean Y, Rain JD. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood. 1997 Nov 1;90(9):3370-7. [http://www.bloodjournal.org/content/90/9/3370.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/9345019 PubMed]
 
−
## '''Update:''' Kiladjian JJ, Chevret S, Dosquet C, Chomienne C, Rain JD. Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980. J Clin Oncol. 2011 Oct 10;29(29):3907-13. Epub 2011 Sep 12. [https://doi.org/10.1200/JCO.2011.36.0792 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21911721 PubMed]
 
−
# '''CYTO-PV:''' Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, De Stefano V, Elli E, Iurlo A, Latagliata R, Lunghi F, Lunghi M, Marfisi RM, Musto P, Masciulli A, Musolino C, Cascavilla N, Quarta G, Randi ML, Rapezzi D, Ruggeri M, Rumi E, Scortechini AR, Santini S, Scarano M, Siragusa S, Spadea A, Tieghi A, Angelucci E, Visani G, Vannucchi AM, Barbui T; CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013 Jan 3;368(1):22-33. Epub 2012 Dec 8. [https://doi.org/10.1056/nejmoa1208500 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23216616 PubMed] NCT01645124
 
−
# '''PROUD-PV:''' Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, Rossiev V, Dulicek P, Illes A, Pylypenko H, Sivcheva L, Mayer J, Yablokova V, Krejcy K, Grohmann-Izay B, Hasselbalch HC, Kralovics R, Kiladjian JJ; PROUD-PV Study Group. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020 Mar;7(3):e196-e208. Epub 2020 Jan 31. [https://doi.org/10.1016/s2352-3026(19)30236-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32014125 PubMed] NCT01949805
 
−
# '''MPD-RC 112:''' Mascarenhas J, Kosiorek HE, Prchal JT, Rambaldi A, Berenzon D, Yacoub A, Harrison CN, McMullin MF, Vannucchi AM, Ewing J, O'Connell CL, Kiladjian JJ, Mead AJ, Winton EF, Leibowitz DS, De Stefano V, Arcasoy MO, Kessler CM, Catchatourian R, Rondelli D, Silver RT, Bacigalupo A, Nagler A, Kremyanskaya M, Levine MF, Arango Ossa JE, McGovern E, Sandy L, Salama ME, Najfeld V, Tripodi J, Farnoud N, Penson AV, Weinberg RS, Price L, Goldberg JD, Barbui T, Marchioli R, Tognoni G, Rampal RK, Mesa RA, Dueck AC, Hoffman R. A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia. Blood. 2022 May 12;139(19):2931-2941. [https://doi.org/10.1182/blood.2021012743 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35007321/ PubMed] NCT01259856
 
−
==Placebo==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa035572 Landolfi et al. 2004 (ECLAP)]
 
−
|1998-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Aspirin_monotherapy|Aspirin]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior combined outcome
 
−
|-
 
−
|}
 
−
''No active treatment.''
 
−
</div></div>
 
−
===References===
 
−
# '''ECLAP:''' Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. [https://doi.org/10.1056/nejmoa035572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14711910 PubMed]
 
−
==Ropeginterferon alfa-2b monotherapy {{#subobject:5kgix4|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:cob120|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s2352-3026(19)30236-4 Gisslinger et al. 2020 (PROUD-PV)]
 
−
|2013-2015
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
−
|[[#Hydroxyurea_monotherapy|Hydroxyurea]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior composite endpoint
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Ropeginterferon alfa-2b (Besremi)]]
 
−
</div></div>
 
−
===References===
 
−
# '''PROUD-PV:''' Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, Rossiev V, Dulicek P, Illes A, Pylypenko H, Sivcheva L, Mayer J, Yablokova V, Krejcy K, Grohmann-Izay B, Hasselbalch HC, Kralovics R, Kiladjian JJ; PROUD-PV Study Group. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020 Mar;7(3):e196-e208. Epub 2020 Jan 31. [https://doi.org/10.1016/s2352-3026(19)30236-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32014125 PubMed] NCT01949805
 
−
=Relapsed, refractory, or intolerant=
 
−
==Anagrelide monotherapy {{#subobject:7c6a2d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:50dda2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
 
−
|2010-2013
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
 
−
|style="background-color:#d73027"|Inferior disease control
 
−
|-
 
−
|}
 
−
To be completed
 
−
====Anticoagulation====
 
−
*[[Anagrelide (Agrylin)]]
 
−
</div></div>
 
−
===References===
 
−
# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
 
−
## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
 
−
## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
 
−
==Hydroxyurea monotherapy {{#subobject:82ab4d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:14ace8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
 
−
|2010-2013
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
 
−
|style="background-color:#d73027"|Inferior disease control
 
−
|-
 
−
|}
 
−
''The following is the approach recommended by Vannucchi in How I Treat (2014).''
 
−
====Chemotherapy====
 
−
*[[Hydroxyurea (Hydrea)]] 500 mg PO twice per day, with titration based on the target hematocrit and hematologic toxicity
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
 
−
## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
 
−
## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
 
−
==Lenalidomide monotherapy {{#subobject:0dd38f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b51df3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
 
−
|2010-2013
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
 
−
|style="background-color:#d73027"|Inferior disease control
 
−
|-
 
−
|}
 
−
To be completed
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]]
 
−
</div></div>
 
−
===References===
 
−
# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
 
−
## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
 
−
## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
 
−
==Peginterferon alfa-2a monotherapy {{#subobject:2519d0|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 45 mcg starting dose {{#subobject:8615e6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6839950/ Yacoub et al. 2019 (MPD-RC-111)]
 
−
|2012-2015
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Peginterferon alfa-2a (Pegasys)]] 45 mcg SC once per day on days 1, 8, 15, 22
 
−
**Titrated up by 45 mcg every month in the absence of toxicity to goal dose of 180 mcg
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 90 mcg starting dose {{#subobject:868ce6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/112/8/3065.long Kiladjian et al. 2008 (PVN1)]
 
−
|2004-2005
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881362/ Quintás-Cardama et al. 2009 (MDACC DM03-0109)]
 
−
|2005-2009
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Quintás-Cardama et al. 2009 does not provide guidance on dose escalation or target dosing. Kiladjian et al. 2008 does not provide details on the dose escalation procedure.''
 
−
====Immunotherapy====
 
−
*[[Peginterferon alfa-2a (Pegasys)]] 90 mcg SC once per day on days 1, 8, 15, 22
 
−
**Titrated up every two weeks in the absence of toxicity to 135 mcg SC once per day on days 1, 8, 15, 22
 
−
**In the absence of hematologic response, dose increased to 180 mcg SC once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 100 mg PO once per day unless intolerant (Kiladjian et al. 2008)
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- no pre-pub disclosed -->
 
−
# '''PVN1:''' Kiladjian JJ, Cassinat B, Chevret S, Turlure P, Cambier N, Roussel M, Bellucci S, Grandchamp B, Chomienne C, Fenaux P. Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood. 2008 Oct 15;112(8):3065-72. Epub 2008 Jul 23. [http://www.bloodjournal.org/content/112/8/3065.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18650451 PubMed] NCT00241241
 
−
<!-- no pre-pub disclosed -->
 
−
# '''MDACC DM03-0109:''' Quintás-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S, Richie MA, Borthakur G, Konopleva M, Cortes J, Verstovsek S. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol. 2009 Nov 10;27(32):5418-24. Epub 2009 Oct 13. [https://doi.org/10.1200/jco.2009.23.6075 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881362/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19826111 PubMed] NCT00452023
 
−
## '''Update:''' Quintás-Cardama A, Abdel-Wahab O, Manshouri T, Kilpivaara O, Cortes J, Roupie AL, Zhang SJ, Harris D, Estrov Z, Kantarjian H, Levine RL, Verstovsek S. Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. Blood. 2013 Aug 8;122(6):893-901. Epub 2013 Jun 19. [http://www.bloodjournal.org/content/122/6/893.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739035/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23782935 PubMed]
 
−
## '''Update:''' Masarova L, Patel KP, Newberry KJ, Cortes J, Borthakur G, Konopleva M, Estrov Z, Kantarjian H, Verstovsek S. Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial. Lancet Haematol. 2017 Apr;4(4):e165-e175. Epub 2017 Mar 10. [https://doi.org/10.1016/S2352-3026(17)30030-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421384/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28291640 PubMed]
 
−
# '''MPD-RC-111:''' Yacoub A, Mascarenhas J, Kosiorek H, Prchal JT, Berenzon D, Baer MR, Ritchie E, Silver RT, Kessler C, Winton E, Finazzi MC, Rambaldi A, Vannucchi AM, Leibowitz D, Rondelli D, Arcasoy MO, Catchatourian R, Vadakara J, Rosti V, Hexner E, Kremyanskaya M, Sandy L, Tripodi J, Najfeld V, Farnoud N, Papaemmanuil E, Salama M, Singer-Weinberg R, Rampal R, Goldberg JD, Barbui T, Mesa R, Dueck AC, Hoffman R. Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea. Blood. 2019 Oct 31;134(18):1498-1509. [https://doi.org/10.1182/blood.2019000428 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6839950/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31515250 PubMed] NCT01259856
 
−
==Pipobroman monotherapy {{#subobject:f9eb67|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:26b5d3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
 
−
|2010-2013
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
 
−
|style="background-color:#d73027"|Inferior disease control
 
−
|-
 
−
|}
 
−
To be completed for historical reference
 
−
====Chemotherapy====
 
−
*[[Pipobroman (Vercyte)]]
 
−
</div></div>
 
−
===References===
 
−
# '''Review:''' Passamonti F, Lazzarino M. Treatment of polycythemia vera and essential thrombocythemia: the role of pipobroman. Leuk Lymphoma. 2003 Sep;44(9):1483-8. [http://www.tandfonline.com/doi/full/10.3109/10428190309178768 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14565648 PubMed]
 
−
# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
 
−
## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
 
−
## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
 
−
==Ruxolitinib monotherapy {{#subobject:f35a21|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:364cac|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231215/ Verstovsek et al. 2014 (INCB18424-256)]
 
−
|2008-NR
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
 
−
|2010-2013
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
 
−
|Standard therapy
 
−
|style="background-color:#1a9850"|Superior disease control
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(16)30558-7 Passamonti et al. 2016 (RESPONSE-2)]
 
−
|2014-2015
 
−
|style="background-color:#1a9851"|Phase 3b (E-switch-ooc)
 
−
|Standard therapy
 
−
|style="background-color:#1a9850"|Superior disease control
 
−
|-
 
−
|}
 
−
''There were several doses evaluated in INCB18424-256; the median total daily dose was 21.7 mg corresponding to approximately 10 mg PO twice per day. The most common comparator in RESPONSE and RESPONSE-2 was [[#Hydroxyurea_monotherapy_2|hydroxyurea]].''
 
−
====Targeted therapy====
 
−
*[[Ruxolitinib (Jakafi)]] 10 mg PO twice per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''INCB18424-256:''' Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rosen PJ, Rumi E, Gattoni E, Pieri L, Guglielmelli P, Elena C, He S, Contel N, Mookerjee B, Sandor V, Cazzola M, Kantarjian HM, Barbui T, Vannucchi AM. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 Inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. Cancer. 2014 Feb 15;120(4):513-20. [https://doi.org/10.1002/cncr.28441 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231215/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24258498 PubMed] content property of [http://hemonc.org HemOnc.org] NCT00726232
 
−
# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
 
−
<!-- ## '''Update: Abstract:''' Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Martin Griesshammer, Tamas Masszi, Simon Durrant, Francesco Passamonti, Claire N. Harrison, Fabrizio Pane, Pierre Zachee, Keita Kirito, Mario Cazzola, Carlos Besses, Igor Blau, Ruben Mesa, Mark M. Jones, Shui He, Huiling Zhen, Jingjin Li, Nathalie Francillard, Dany Habr, Srdan Verstovsek. Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the response trial. EHA 2015 Abstract: S447 [http://learningcenter.ehaweb.org/eha/2015/20th/103108/jean-jacques.kiladjian.ruxolitinib.versus.best.available.therapy.in.patients.html?f=l5449p16m3 link to abstract] -->
 
−
## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
 
−
## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
 
−
# '''RESPONSE-2:''' Passamonti F, Griesshammer M, Palandri F, Egyed M, Benevolo G, Devos T, Callum J, Vannucchi AM, Sivgin S, Bensasson C, Khan M, Mounedji N, Saydam G. Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol. 2017 Jan;18(1):88-99. Epub 2016 Dec 2. [https://doi.org/10.1016/S1470-2045(16)30558-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27916398 PubMed] NCT02038036
 
−
##'''Update:''' Passamonti F, Palandri F, Saydam G, Callum J, Devos T, Guglielmelli P, Vannucchi AM, Zor E, Zuurman M, Gilotti G, Zhang Y, Griesshammer M. Ruxolitinib versus best available therapy in inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): 5-year follow up of a randomised, phase 3b study. Lancet Haematol. 2022 Jul;9(7):e480-e492. Epub 2022 May 18. [https://doi.org/10.1016/s2352-3026(22)00102-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35597252/ PubMed]
 
−
==Thalidomide monotherapy {{#subobject:cfd2c6|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:63b4bf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
 
−
|2010-2013
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
 
−
|style="background-color:#d73027"|Inferior disease control
 
−
|-
 
−
|}
 
−
To be completed
 
−
====Targeted therapy====
 
−
*[[Thalidomide (Thalomid)]]
 
−
</div></div>
 
−
===References===
 
−
# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
 
−
## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
 
−
## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
 
−
=Response criteria=
 
−
==ELN==
 
−
*'''2009:''' [http://www.bloodjournal.org/content/113/20/4829.long Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference]
 
−
[[Category:Polycythemia vera regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Myeloproliferative neoplasms]]
 

Latest revision as of 00:13, 18 June 2023

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