Difference between revisions of "Polycythemia vera"

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'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].''' 
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Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
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[[#top|Back to Top]]
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</div>
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{{#lst:Editorial board transclusions|mpn}}
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''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Polycythemia vera - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
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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: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} variants 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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*''We have moved [[How I Treat]] articles to a dedicated page.''
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
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=Guidelines=
 +
'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
 +
==ELN==
 +
*'''2011:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979120/ Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet] [https://www.ncbi.nlm.nih.gov/pubmed/21205761 PubMed]
  
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=Relapsed, refractory, or intolerant=
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==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] [https://www.ncbi.nlm.nih.gov/pubmed/26242182 PubMed]
  
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==Anagrelide (Agrylin) {{#subobject:7c6a2d|Regimen=1}}==
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==NCCN==
 +
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1477 NCCN Guidelines - Myeloproliferative Neoplasms].''
  
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===Regimen {{#subobject:50dda2|Variant=1}}===
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=First-line therapy=
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{| border="1" style="text-align:center;" !align="left"  
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==Aspirin monotherapy {{#subobject:5c9446|Regimen=1}}==
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|'''Study'''
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<div class="toccolours" style="background-color:#eeeeee">
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|[[Levels_of_Evidence#Evidence|'''Evidence''']]
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===Regimen {{#subobject:3983e0|Variant=1}}===
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|'''Comparator'''
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{| class="wikitable sortable" style="width: 100%; text-align:center;"  
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|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
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!style="width: 20%"|Study
 +
!style="width: 20%"|Dates 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.nejm.org/doi/full/10.1056/NEJMoa1409002 Vannucchi et al. 2015 (RESPONSE)]
+
|[https://doi.org/10.1056/nejmoa035572 Landolfi et al. 2004 (ECLAP)]
−
|style="background-color:#00CD00"|Phase III
+
|1998-2000
−
|[[Polycythemia_vera#Ruxolitinib_.28Jakafi.29|Ruxolitinib]]
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| style="background-color:#1a9851" |Phase 3 (E-esc)
−
|style="background-color:#ff0000"|Inferior disease control
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|[[Polycythemia_vera_-_null_regimens#Placebo|Placebo]]
 +
| style="background-color:#91cf60" |Seems to have superior combined outcome (co-primary endpoint)
 
|-
 
|-
 
|}
 
|}
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To be completed
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<div class="toccolours" style="background-color:#b3e2cd">
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====Anticoagulation====
 +
*[[Aspirin]] 100 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div>
 
===References===
 
===References===
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1409002 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25629741 PubMed]
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# '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14711910/ PubMed]
  
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==Hydroxyurea (Hydrea) {{#subobject:82ab4d|Regimen=1}}==
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==Hydroxyurea monotherapy {{#subobject:511984|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
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===Regimen {{#subobject:14ace8|Variant=1}}===
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===Regimen {{#subobject:84f020|Variant=1}}===
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{| border="1" style="text-align:center;" !align="left"  
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{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
|'''Study'''
+
!style="width: 20%"|Study
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
!style="width: 20%"|Dates of enrollment
−
|'''Comparator'''
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!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
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|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
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!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_888|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 endpoint
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9101248/ Mascarenhas et al. 2022 (MPD-RC 112)]
 +
|2011-2016
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Peginterferon_alfa-2a_monotherapy_999|Peginterferon alfa-2a]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of CHR rate
 
|-
 
|-
−
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1409002 Vannucchi et al. 2015 (RESPONSE)]
+
|[https://doi.org/10.1016/s2352-3026(19)30236-4 Gisslinger et al. 2020 (PROUD-PV)]
−
|style="background-color:#00CD00"|Phase III
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|2013-2015
−
|[[Polycythemia_vera#Ruxolitinib_.28Jakafi.29|Ruxolitinib]]
+
|style="background-color:#1a9851"|Phase 3 (C)
−
|style="background-color:#ff0000"|Inferior disease control
+
|[[#Ropeginterferon_alfa-2b_monotherapy|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).''
+
''Note: The following is the approach recommended by Vannucchi in How I Treat (2014).''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Hydroxyurea (Hydrea)]] 500 mg PO BID, with titration based on the target hematocrit and hematologic toxicity
+
*[[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>
  
−
'''Continued until treatment failure or intolerance'''
+
===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] [https://clinicaltrials.gov/study/NCT01645124 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] [https://clinicaltrials.gov/study/NCT01949805 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. Epub 2022 Jan 10. [https://doi.org/10.1182/blood.2021012743 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9101248/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35007321/ PubMed] [https://clinicaltrials.gov/study/NCT01259856 NCT01259856]
  
 +
==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%"|Dates 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/PMC4608390/ Gisslinger et al. 2015 (PEGINVERA)]
 +
|NR
 +
| style="background-color:#91cf61" |Phase 1/2 (RT)
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[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 (co-primary endpoint)
 +
|-
 +
|}
 +
''Note: this dose was the MTD determined in PEGINVERA.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Ropeginterferon alfa-2b (Besremi)]] 540 mcg SC once on day 1
 +
'''14-day cycles'''
 +
</div></div>
 
===References===
 
===References===
−
# 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://www.ncbi.nlm.nih.gov/pubmed/25278584 PubMed]
+
# '''PEGINVERA:''' Gisslinger H, Zagrijtschuk O, Buxhofer-Ausch V, Thaler J, Schloegl E, Gastl GA, Wolf D, Kralovics R, Gisslinger B, Strecker K, Egle A, Melchardt T, Burgstaller S, Willenbacher E, Schalling M, Them NC, Kadlecova P, Klade C, Greil R. Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera. Blood. 2015 Oct 8;126(15):1762-9. Epub 2015 Aug 10. [http://www.bloodjournal.org/content/126/15/1762.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608390/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26261238/ PubMed] [https://clinicaltrials.gov/study/NCT01193699 NCT01193699]
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1409002 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25629741 PubMed]
+
# '''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] [https://clinicaltrials.gov/study/NCT01949805 NCT01949805]
  
−
==Peginterferon alfa-2a (Pegasys) {{#subobject:2519d0|Regimen=1}}==
+
=Relapsed, refractory, or intolerant=
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
==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%"|Dates 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
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====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] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] '''does not contain dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25629741/ PubMed] [https://clinicaltrials.gov/study/NCT01243944 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://www.ncbi.nlm.nih.gov/pmc/articles/pmc8938906/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31982039/ PubMed]
  
−
===Regimen {{#subobject:868ce6|Variant=1}}===
+
==Hydroxyurea monotherapy {{#subobject:82ab4d|Regimen=1}}==
−
{| border="1" style="text-align:center;" !align="left"  
+
<div class="toccolours" style="background-color:#eeeeee">
−
|'''Study'''
+
===Regimen {{#subobject:14ace8|Variant=1}}===
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates 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
 +
|-
 +
|}
 +
''Note: The following is the approach recommended by Vannucchi in How I Treat (2014).''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====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] [https://clinicaltrials.gov/study/NCT01243944 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://www.ncbi.nlm.nih.gov/pmc/articles/pmc8938906/ link to PMC 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%"|Dates 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
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====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] [https://clinicaltrials.gov/study/NCT01243944 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://www.ncbi.nlm.nih.gov/pmc/articles/pmc8938906/ link to PMC 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%"|Dates 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
 +
|-
 +
|}
 +
''Note: Titration occurred in the absence of toxicity.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Peginterferon alfa-2a (Pegasys)]] as follows:
 +
**Cycles 1 to 4: 45 mcg SC once on day 1
 +
**Cycles 5 to 8: 90 mcg SC once on day 1
 +
**Cycles 9 to 12: 135 mcg SC once on day 1
 +
**Cycle 13 onwards: 180 mcg SC once on day 1
 +
'''7-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%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
 
|[http://www.bloodjournal.org/content/112/8/3065.long Kiladjian et al. 2008 (PVN1)]
 
|[http://www.bloodjournal.org/content/112/8/3065.long Kiladjian et al. 2008 (PVN1)]
−
|style="background-color:#EEEE00"|Phase II
+
|2004-2005
 +
|style="background-color:#91cf61"|Phase 2
 
|-
 
|-
−
|[http://jco.ascopubs.org/content/27/32/5418.long Quintás-Cardama et al. 2009]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881362/ Quintás-Cardama et al. 2009 (MDACC DM03-0109)]
−
|style="background-color:#EEEE00"|Phase II
+
|2005-2009
 +
|style="background-color:#91cf61"|Phase 2
 
|-
 
|-
 
|}
 
|}
−
 
+
''Note: 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.''
−
''Quintás-Cardama et al. 2009 do not provide guidance on dose escalation or target dosing. Kiladjian et al. 2008 do not provide details on the dose escalation procedure.''
+
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
−
*[[Peginterferon alfa-2a (Pegasys)]] 90 mcg SC once per week, titrated up every two weeks in the absence of toxicity to 135 mg SC once per week
+
*[[Peginterferon alfa-2a (Pegasys)]] 90 mcg SC once per day on days 1, 8, 15, 22 (see titration instructions below)
−
**In the absence of hematologic response, dose increased to 180 mg SC once per week
+
====Supportive therapy====
−
 
 
−
====Supportive medications====
 
 
*[[Aspirin]] 100 mg PO once per day unless intolerant (Kiladjian et al. 2008)
 
*[[Aspirin]] 100 mg PO once per day unless intolerant (Kiladjian et al. 2008)
−
 
+
'''28-day cycles'''
−
'''Unspecified duration'''
+
</div>
 +
<div class="toccolours" style="background-color:#fff2ae">
 +
====Dose and schedule modifications====
 +
*Peginterferon alfa-2a dose 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, peginterferon alfa-2a dose increased to 180 mcg SC once per day on days 1, 8, 15, 22
 +
</div></div>
  
 
===References===
 
===References===
 
<!-- no pre-pub disclosed -->
 
<!-- no pre-pub disclosed -->
−
# 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18650451 PubMed]
+
# '''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] [https://clinicaltrials.gov/study/NCT00241241 NCT00241241]
 
<!-- no pre-pub disclosed -->
 
<!-- no pre-pub disclosed -->
−
# 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. [http://jco.ascopubs.org/content/27/32/5418.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19826111 PubMed]
+
# '''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] [https://clinicaltrials.gov/study/NCT00452023 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/pubmed/23782935 PubMed]
+
## '''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 Mar 10. [Epub ahead of print] [http://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30030-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28291640 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] [https://clinicaltrials.gov/study/NCT01259856 NCT01259856]
−
==Ruxolitinib (Jakafi) {{#subobject:f35a21|Regimen=1}}==
+
==Pipobroman monotherapy {{#subobject:f9eb67|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<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%"|Dates 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
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====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] '''does not contain 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] [https://clinicaltrials.gov/study/NCT01243944 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://www.ncbi.nlm.nih.gov/pmc/articles/pmc8938906/ link to PMC 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}}===
 
===Regimen {{#subobject:364cac|Variant=1}}===
−
{| border="1" style="text-align:center;" !align="left"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
|'''Study'''
+
!style="width: 20%"|Study
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
!style="width: 20%"|Dates of enrollment
−
|'''Comparator'''
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.28441/full Verstovsek et al. 2014]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231215/ Verstovsek et al. 2014 (INCB 18424-256<sub>PV</sub>)]
−
|style="background-color:#EEEE00"|Phase II
+
|2008-07 to 2009-04
 +
|style="background-color:#91cf61"|Phase 2
 
|style="background-color:#d3d3d3"|
 
|style="background-color:#d3d3d3"|
 
|style="background-color:#d3d3d3"|
 
|style="background-color:#d3d3d3"|
 
|-
 
|-
−
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1409002 Vannucchi et al. 2015 (RESPONSE)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
−
|style="background-color:#00CD00"|Phase III
+
|2010-2013
 +
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
 
|Standard therapy
 
|Standard therapy
−
|style="background-color:#00CD00"|Superior disease control
+
|style="background-color:#1a9850"|Superior disease control and spleen reduction (primary endpoint)
 
|-
 
|-
−
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30558-7/fulltext Passamonti et al. 2016 (RESPONSE-2)]
+
|[https://doi.org/10.1016/S1470-2045(16)30558-7 Passamonti et al. 2016 (RESPONSE-2)]
−
|style="background-color:#00CD00"|Phase III
+
|2014-03-25 to 2015-02-11
 +
|style="background-color:#1a9851"|Phase 3b (E-switch-ooc)
 
|Standard therapy
 
|Standard therapy
−
|style="background-color:#00CD00"|Superior disease control
+
|style="background-color:#1a9850"|Superior hematocrit control at week 28 (primary endpoint)
 
|-
 
|-
 
|}
 
|}
−
''There were several doses evaluated in Verstovsek et al. 2014; 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 [[Polycythemia_vera#Hydroxyurea_.28Hydrea.29|hydroxyurea]].''
+
''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]].''
−
====Chemotherapy====
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 
*[[Ruxolitinib (Jakafi)]] 10 mg PO twice per day
 
*[[Ruxolitinib (Jakafi)]] 10 mg PO twice per day
 +
'''Continued indefinitely'''
 +
</div></div>
 +
===References===
 +
# '''INCB 18424-256<sub>PV</sub>:''' 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 [https://hemonc.org HemOnc.org] [https://clinicaltrials.gov/study/NCT00726232 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] [https://clinicaltrials.gov/study/NCT01243944 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://www.ncbi.nlm.nih.gov/pmc/articles/pmc8938906/ link to PMC 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] [https://clinicaltrials.gov/study/NCT02038036 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]
  
−
'''Continued until progression or excess toxicity'''
+
==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%"|Dates 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
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Thalidomide (Thalomid)]]
 +
</div></div>
 
===References===
 
===References===
−
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.28441/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24258498 PubMed] content property of [http://hemonc.org HemOnc.org]
+
# '''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] '''does not contain 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] [https://clinicaltrials.gov/study/NCT01243944 NCT01243944]
−
# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1409002 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25629741 PubMed]
+
## '''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: 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:''' 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://www.ncbi.nlm.nih.gov/pmc/articles/pmc8938906/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31982039/ PubMed]
−
## '''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/pubmed/27102499 PubMed]
 
−
# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30558-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27916398 PubMed]
 
  
−
[[Category:Chemotherapy regimens]]
+
=Response criteria=
−
[[Category:Malignant hematology regimens]]
+
==ELN==
−
[[Category:Myeloproliferative neoplasm regimens]]
+
*'''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]]

Revision as of 19:27, 23 June 2024

Back to Top

Section editor
Sanjay mohan.png
 Sanjay R. Mohan, MD, MSCI
Vanderbilt University
Nashville, TN, USA

Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!

10 regimens on this page
11 variants on this page
  • We have moved How I Treat articles to a dedicated page.


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ELN

ESMO

NCCN

First-line therapy

Aspirin monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Landolfi et al. 2004 (ECLAP) 1998-2000 Phase 3 (E-esc) Placebo Seems to have superior combined outcome (co-primary endpoint)

Anticoagulation

Continued indefinitely

References

  1. 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. link to original article contains dosing details in manuscript PubMed

Hydroxyurea monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Najean et al. 1997 (FPSG) 1980-NR Phase 3 (E-switch-ic) Pipobroman Superior OS1
Marchioli et al. 2012 (CYTO-PV) 2008-2012 Phase 3 (E-esc) Hydroxyurea; less strict hematocrit goal Superior primary endpoint
Mascarenhas et al. 2022 (MPD-RC 112) 2011-2016 Phase 3 (C) Peginterferon alfa-2a Did not meet primary endpoint of CHR rate
Gisslinger et al. 2020 (PROUD-PV) 2013-2015 Phase 3 (C) Ropeginterferon alfa-2b Seems to have non-inferior composite endpoint

1Reported efficacy for FPSG is based on the 2011 update.
Note: 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

References

  1. 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. link to original article PubMed
    1. 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. link to original article PubMed
  2. 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. link to original article PubMed NCT01645124
  3. 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. link to original article PubMed NCT01949805
  4. 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. Epub 2022 Jan 10. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01259856

Ropeginterferon alfa-2b monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gisslinger et al. 2015 (PEGINVERA) NR Phase 1/2 (RT)
Gisslinger et al. 2020 (PROUD-PV) 2013-2015 Phase 3 (E-switch-ooc) Hydroxyurea Seems to have non-inferior composite endpoint (co-primary endpoint)

Note: this dose was the MTD determined in PEGINVERA.

Immunotherapy

14-day cycles

References

  1. PEGINVERA: Gisslinger H, Zagrijtschuk O, Buxhofer-Ausch V, Thaler J, Schloegl E, Gastl GA, Wolf D, Kralovics R, Gisslinger B, Strecker K, Egle A, Melchardt T, Burgstaller S, Willenbacher E, Schalling M, Them NC, Kadlecova P, Klade C, Greil R. Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera. Blood. 2015 Oct 8;126(15):1762-9. Epub 2015 Aug 10. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01193699
  2. 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. link to original article PubMed NCT01949805

Relapsed, refractory, or intolerant

Anagrelide monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Vannucchi et al. 2015 (RESPONSE) 2010-2013 Phase 3 (C) Ruxolitinib Inferior disease control

Anticoagulation

References

  1. 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. link to original article link to PMC article does not contain dosing details in manuscript PubMed NCT01243944
    1. 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. link to original article link to PMC article PubMed
    2. 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. link to original article link to PMC article PubMed

Hydroxyurea monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Vannucchi et al. 2015 (RESPONSE) 2010-2013 Phase 3 (C) Ruxolitinib Inferior disease control

Note: 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

References

  1. 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01243944
    1. 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. link to original article link to PMC article PubMed
    2. 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. link to original article link to PMC article PubMed

Lenalidomide monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Vannucchi et al. 2015 (RESPONSE) 2010-2013 Phase 3 (C) Ruxolitinib Inferior disease control

Targeted therapy

References

  1. 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01243944
    1. 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. link to original article link to PMC article PubMed
    2. 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. link to original article link to PMC article PubMed

Peginterferon alfa-2a monotherapy

Regimen variant #1, 45 mcg starting dose

Study Dates of enrollment Evidence
Yacoub et al. 2019 (MPD-RC-111) 2012-2015 Phase 2

Note: Titration occurred in the absence of toxicity.

Immunotherapy

  • Peginterferon alfa-2a (Pegasys) as follows:
    • Cycles 1 to 4: 45 mcg SC once on day 1
    • Cycles 5 to 8: 90 mcg SC once on day 1
    • Cycles 9 to 12: 135 mcg SC once on day 1
    • Cycle 13 onwards: 180 mcg SC once on day 1

7-day cycles


Regimen variant #2, 90 mcg starting dose

Study Dates of enrollment Evidence
Kiladjian et al. 2008 (PVN1) 2004-2005 Phase 2
Quintás-Cardama et al. 2009 (MDACC DM03-0109) 2005-2009 Phase 2

Note: 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

Supportive therapy

  • Aspirin 100 mg PO once per day unless intolerant (Kiladjian et al. 2008)

28-day cycles

Dose and schedule modifications

  • Peginterferon alfa-2a dose 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, peginterferon alfa-2a dose increased to 180 mcg SC once per day on days 1, 8, 15, 22

References

  1. 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. link to original article contains dosing details in manuscript PubMed NCT00241241
  2. 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. link to original article contains dosing details in abstract link to PMC article PubMed NCT00452023
    1. 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. link to original article link to PMC article PubMed
    2. 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. link to original article link to PMC article PubMed
  3. 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01259856

Pipobroman monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Vannucchi et al. 2015 (RESPONSE) 2010-2013 Phase 3 (C) Ruxolitinib Inferior disease control

Chemotherapy

References

  1. Review: Passamonti F, Lazzarino M. Treatment of polycythemia vera and essential thrombocythemia: the role of pipobroman. Leuk Lymphoma. 2003 Sep;44(9):1483-8. link to original article PubMed
  2. 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. link to original article does not contain dosing details in manuscript link to PMC article PubMed NCT01243944
    1. 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. link to original article link to PMC article PubMed
    2. 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. link to original article link to PMC article PubMed

Ruxolitinib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Verstovsek et al. 2014 (INCB 18424-256PV) 2008-07 to 2009-04 Phase 2
Vannucchi et al. 2015 (RESPONSE) 2010-2013 Phase 3 (E-RT-switch-ooc) Standard therapy Superior disease control and spleen reduction (primary endpoint)
Passamonti et al. 2016 (RESPONSE-2) 2014-03-25 to 2015-02-11 Phase 3b (E-switch-ooc) Standard therapy Superior hematocrit control at week 28 (primary endpoint)

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.

Targeted therapy

Continued indefinitely

References

  1. INCB 18424-256PV: 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. link to original article contains dosing details in manuscript link to PMC article PubMed content property of HemOnc.org NCT00726232
  2. 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01243944
    1. 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. link to original article link to PMC article PubMed
    2. 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. link to original article link to PMC article PubMed
  3. 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. link to original article contains dosing details in abstract PubMed NCT02038036
    1. 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. link to original article PubMed

Thalidomide monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Vannucchi et al. 2015 (RESPONSE) 2010-2013 Phase 3 (C) Ruxolitinib Inferior disease control

Targeted therapy

References

  1. 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. link to original article does not contain dosing details in manuscript link to PMC article PubMed NCT01243944
    1. 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. link to original article link to PMC article PubMed
    2. 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. link to original article link to PMC article PubMed

Response criteria

ELN

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