Difference between revisions of "Polycythemia vera"
Warner-admin (talk | contribs) m (Text replacement - "http://www.nejm.org" to "https://www.nejm.org") |
m |
||
(100 intermediate revisions by 4 users not shown) | |||
Line 1: | Line 1: | ||
− | + | <span id="BackToTop"></span> | |
− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | + | [[#top|Back to Top]] | |
− | + | </div> | |
− | + | {{#lst:Editorial board transclusions|mpn}} | |
− | + | ''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;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
Line 11: | Line 10: | ||
<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> | <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> | ||
|} | |} | ||
+ | *''We have moved [[How I Treat]] articles to a dedicated page.'' | ||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
− | |||
=Guidelines= | =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== | ==ELN== | ||
− | *'''2011:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979120/ Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet] | + | *'''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] |
==ESMO== | ==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 | + | *'''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] |
− | |||
− | |||
− | |||
− | == | + | ==NCCN== |
− | *[https://www.nccn.org/ | + | *''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].'' |
=First-line therapy= | =First-line therapy= | ||
==Aspirin monotherapy {{#subobject:5c9446|Regimen=1}}== | ==Aspirin monotherapy {{#subobject:5c9446|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:3983e0|Variant=1}}=== | ===Regimen {{#subobject:3983e0|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/nejmoa035572 Landolfi et al. 2004 (ECLAP)] |
− | | style="background-color:#1a9851" |Phase | + | |1998-2000 |
− | |[[#Placebo|Placebo]] | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | | style="background-color:#91cf60" |Seems to have superior combined outcome | + | |[[Polycythemia_vera_-_null_regimens#Placebo|Placebo]] |
+ | | style="background-color:#91cf60" |Seems to have superior combined outcome (co-primary endpoint) | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | *[[Aspirin]] 100 mg once per day | + | ====Anticoagulation==== |
− | + | *[[Aspirin]] 100 mg PO once per day | |
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
+ | </div></div> | ||
===References=== | ===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:// | + | # '''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] |
==Hydroxyurea monotherapy {{#subobject:511984|Regimen=1}}== | ==Hydroxyurea monotherapy {{#subobject:511984|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <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%"|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://doi.org/10.1182/blood.V90.9.3370 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)] |
− | |style="background-color:#1a9851"|Phase | + | |2011-2016 |
− | | | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |[[#Peginterferon_alfa-2a_monotherapy_999|Peginterferon alfa-2a]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of CHR rate | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/s2352-3026(19)30236-4 Gisslinger et al. 2020 (PROUD-PV)] |
− | |style="background-color:#1a9851"|Phase | + | |2013-2015 |
− | | | + | |style="background-color:#1a9851"|Phase 3 (C) |
− | |style="background-color:# | + | |[[#Ropeginterferon_alfa-2b_monotherapy|Ropeginterferon alfa-2b]] |
+ | | style="background-color:#eeee01" |Seems to have non-inferior composite endpoint | ||
|- | |- | ||
|} | |} | ||
− | ''The following is the approach recommended by Vannucchi in How I Treat (2014) | + | ''<sup>1</sup>Reported efficacy for FPSG is based on the 2011 update.''<br> |
+ | ''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 | + | *[[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''' | '''Continued indefinitely''' | ||
+ | </div></div> | ||
===References=== | ===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. [ | + | # '''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. [https://doi.org/10.1182/blood.V90.9.3370 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. [ | + | ## '''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:// | + | # '''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}}== |
− | {| class="wikitable" style=" | + | <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:// | + | |[https://doi.org/10.1016/s2352-3026(19)30236-4 Gisslinger et al. 2020 (PROUD-PV)] |
− | | style="background-color:#1a9851" |Phase | + | |2013-2015 |
− | |[[# | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) |
− | | style="background-color:# | + | |[[#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=== | ||
− | # ''' | + | # '''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. [https://doi.org/10.1182/blood-2015-04-637280 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] |
+ | # '''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] | ||
=Relapsed, refractory, or intolerant= | =Relapsed, refractory, or intolerant= | ||
− | |||
==Anagrelide monotherapy {{#subobject:7c6a2d|Regimen=1}}== | ==Anagrelide monotherapy {{#subobject:7c6a2d|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:50dda2|Variant=1}}=== | ===Regimen {{#subobject:50dda2|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !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)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)] | ||
− | |style="background-color:#1a9851"|Phase | + | |2010-2013 |
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
|[[#Ruxolitinib_monotherapy|Ruxolitinib]] | |[[#Ruxolitinib_monotherapy|Ruxolitinib]] | ||
|style="background-color:#d73027"|Inferior disease control | |style="background-color:#d73027"|Inferior disease control | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ==== | + | ====Anticoagulation==== |
*[[Anagrelide (Agrylin)]] | *[[Anagrelide (Agrylin)]] | ||
− | + | </div></div> | |
===References=== | ===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:// | + | # '''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. [ | + | ## '''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. [https://doi.org/10.3324/haematol.2016.143644 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] | ||
==Hydroxyurea monotherapy {{#subobject:82ab4d|Regimen=1}}== | ==Hydroxyurea monotherapy {{#subobject:82ab4d|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:14ace8|Variant=1}}=== | ===Regimen {{#subobject:14ace8|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !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)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)] | ||
− | |style="background-color:#1a9851"|Phase | + | |2010-2013 |
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
|[[#Ruxolitinib_monotherapy|Ruxolitinib]] | |[[#Ruxolitinib_monotherapy|Ruxolitinib]] | ||
|style="background-color:#d73027"|Inferior disease control | |style="background-color:#d73027"|Inferior disease control | ||
|- | |- | ||
|} | |} | ||
− | + | ''Note: The following is the approach recommended by Vannucchi in How I Treat (2014).'' | |
− | ''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 | + | *[[Hydroxyurea (Hydrea)]] 500 mg PO twice per day, with titration based on the target hematocrit and hematologic toxicity |
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===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:// | + | # '''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. [ | + | ## '''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. [https://doi.org/10.3324/haematol.2016.143644 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}}== | ==Lenalidomide monotherapy {{#subobject:0dd38f|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:b51df3|Variant=1}}=== | ===Regimen {{#subobject:b51df3|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !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)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)] | ||
− | |style="background-color:#1a9851"|Phase | + | |2010-2013 |
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
|[[#Ruxolitinib_monotherapy|Ruxolitinib]] | |[[#Ruxolitinib_monotherapy|Ruxolitinib]] | ||
|style="background-color:#d73027"|Inferior disease control | |style="background-color:#d73027"|Inferior disease control | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ==== | + | ====Targeted therapy==== |
*[[Lenalidomide (Revlimid)]] | *[[Lenalidomide (Revlimid)]] | ||
− | + | </div></div> | |
===References=== | ===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:// | + | # '''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. [ | + | ## '''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. [https://doi.org/10.3324/haematol.2016.143644 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}}== | ==Peginterferon alfa-2a monotherapy {{#subobject:2519d0|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <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 | ||
|- | |- | ||
− | |||
|} | |} | ||
− | ===Regimen {{#subobject:868ce6|Variant=1}}=== | + | ''Note: Titration occurred in the absence of toxicity.'' |
− | {| class="wikitable" style="width: | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | !style="width: | + | ====Immunotherapy==== |
− | !style="width: | + | *[[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]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2008-03-143537 Kiladjian et al. 2008 (PVN1)] |
− | |style="background-color:#91cf61"|Phase | + | |2004-2005 |
+ | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881362/ 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:#91cf61"|Phase | + | |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 | + | <div class="toccolours" style="background-color:#b3e2cd"> |
====Immunotherapy==== | ====Immunotherapy==== | ||
− | *[[Peginterferon alfa-2a (Pegasys)]] 90 mcg SC once per | + | *[[Peginterferon alfa-2a (Pegasys)]] 90 mcg SC once per day on days 1, 8, 15, 22 (see titration instructions below) |
− | + | ====Supportive therapy==== | |
− | |||
− | ====Supportive | ||
*[[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''' | |
− | ''' | + | </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 --> | ||
− | # '''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. [ | + | # '''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. [https://doi.org/10.1182/blood-2008-03-143537 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. [ | + | # '''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. [ | + | ## '''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. [https://doi.org/10.1182/blood-2012-07-442012 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:// | + | ## '''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] | |
==Pipobroman monotherapy {{#subobject:f9eb67|Regimen=1}}== | ==Pipobroman monotherapy {{#subobject:f9eb67|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:26b5d3|Variant=1}}=== | ===Regimen {{#subobject:26b5d3|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !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)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)] | ||
− | |style="background-color:#1a9851"|Phase | + | |2010-2013 |
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
|[[#Ruxolitinib_monotherapy|Ruxolitinib]] | |[[#Ruxolitinib_monotherapy|Ruxolitinib]] | ||
|style="background-color:#d73027"|Inferior disease control | |style="background-color:#d73027"|Inferior disease control | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Pipobroman (Vercyte)]] | *[[Pipobroman (Vercyte)]] | ||
− | + | </div></div> | |
===References=== | ===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. [ | + | # '''Review:''' Passamonti F, Lazzarino M. Treatment of polycythemia vera and essential thrombocythemia: the role of pipobroman. Leuk Lymphoma. 2003 Sep;44(9):1483-8. [https://doi.org/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:// | + | # '''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. [ | + | ## '''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. [https://doi.org/10.3324/haematol.2016.143644 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}}== | ==Ruxolitinib monotherapy {{#subobject:f35a21|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:364cac|Variant=1}}=== | ===Regimen {{#subobject:364cac|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !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] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231215/ Verstovsek et al. 2014 (INCB 18424-256<sub>PV</sub>)] |
− | |style="background-color:#91cf61"|Phase | + | |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"| | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)] | ||
− | |style="background-color:#1a9851"|Phase | + | |2010-2013 |
+ | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc) | ||
|Standard therapy | |Standard therapy | ||
− | |style="background-color:#1a9850"|Superior disease control | + | |style="background-color:#1a9850"|Superior disease control and spleen reduction (primary endpoint) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(16)30558-7 Passamonti et al. 2016 (RESPONSE-2)] |
− | |style="background-color:#1a9851"|Phase | + | |2014-03-25 to 2015-02-11 |
+ | |style="background-color:#1a9851"|Phase 3b (E-switch-ooc) | ||
|Standard therapy | |Standard therapy | ||
− | |style="background-color:#1a9850"|Superior | + | |style="background-color:#1a9850"|Superior hematocrit control at week 28 (primary endpoint) |
|- | |- | ||
|} | |} | ||
− | ''There were several doses evaluated in | + | ''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]].'' |
− | ==== | + | <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''' | '''Continued indefinitely''' | ||
− | + | </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. [https:// | + | # '''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:// | + | # '''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 | + | <!-- ## '''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--> |
− | ## '''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. [ | + | ## '''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. [https://doi.org/10.3324/haematol.2016.143644 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] |
− | # '''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:// | + | ## '''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] | ||
==Thalidomide monotherapy {{#subobject:cfd2c6|Regimen=1}}== | ==Thalidomide monotherapy {{#subobject:cfd2c6|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:63b4bf|Variant=1}}=== | ===Regimen {{#subobject:63b4bf|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !style="width: 20%"|Dates of enrollment |
− | !style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | !style="width: | + | !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)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)] | ||
− | |style="background-color:#1a9851"|Phase | + | |2010-2013 |
+ | |style="background-color:#1a9851"|Phase 3 (C) | ||
|[[#Ruxolitinib_monotherapy|Ruxolitinib]] | |[[#Ruxolitinib_monotherapy|Ruxolitinib]] | ||
|style="background-color:#d73027"|Inferior disease control | |style="background-color:#d73027"|Inferior disease control | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ==== | + | ====Targeted therapy==== |
*[[Thalidomide (Thalomid)]] | *[[Thalidomide (Thalomid)]] | ||
− | + | </div></div> | |
===References=== | ===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:// | + | # '''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. [ | + | ## '''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. [https://doi.org/10.3324/haematol.2016.143644 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 criteria= | =Response criteria= | ||
==ELN== | ==ELN== | ||
− | *'''2009:''' [ | + | *'''2009:''' [https://doi.org/10.1182/blood-2008-09-176818 Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference] |
− | |||
[[Category:Polycythemia vera regimens]] | [[Category:Polycythemia vera regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Myeloproliferative neoplasms]] | [[Category:Myeloproliferative neoplasms]] |
Latest revision as of 23:43, 26 June 2024
Section editor | |
---|---|
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
- 2011: Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet PubMed
ESMO
- 2015: Vannucchi et al. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Myeloproliferative Neoplasms.
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) |
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. 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
- 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
- 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
- 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
- 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
- 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.
References
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Peginterferon alfa-2a (Pegasys) 90 mcg SC once per day on days 1, 8, 15, 22 (see titration instructions below)
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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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.
References
- 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
- 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
- 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
- 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-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
- 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
- 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
- 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
- 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