Difference between revisions of "Polycythemia vera"

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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] [https://pubmed.ncbi.nlm.nih.gov/14711910 PubMed]
 
# '''ECLAP:''' Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. [https://doi.org/10.1056/nejmoa035572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14711910 PubMed]
  
−
==Ropeginterferon alfa-2b monotherapy {{#subobject:5obk84|Regimen=1}}==
+
==Hydroxyurea monotherapy {{#subobject:511984|Regimen=1}}==
  
−
===Regimen {{#subobject:84ob19|Variant=1}}===
+
===Regimen {{#subobject:84f020|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
Line 65: Line 65:
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[http://www.bloodjournal.org/content/90/9/3370.long Najean et al. 1997 (FPSG)]
 +
|1980-NR
 +
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 +
|[[#Pipobroman_monotherapy_88|Pipobroman]]
 +
|style="background-color:#1a9850"|Superior OS<sup>1</sup>
 +
|-
 +
|[https://doi.org/10.1056/nejmoa1208500 Marchioli et al. 2012 (CYTO-PV)]
 +
|2008-2012
 +
|style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|[[#Hydroxyurea_monotherapy|Hydroxyurea]]; less strict hematocrit goal
 +
|style="background-color:#1a9850"|Superior primary endpont
 +
|-
 +
|[https://doi.org/10.1182/blood.2021012743 Mascarenhas et al. 2022 (MPD-RC 112)]
 +
|2011-2016
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Pegintereron_alfa-2a_monotherapy_99|Peginterferon alfa-2a]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of CHR rate
 
|-
 
|-
 
|[https://doi.org/10.1016/s2352-3026(19)30236-4 Gisslinger et al. 2020 (PROUD-PV)]
 
|[https://doi.org/10.1016/s2352-3026(19)30236-4 Gisslinger et al. 2020 (PROUD-PV)]
 
|2013-2015
 
|2013-2015
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
+
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#Hydroxyurea_monotherapy|Hydroxyurea]]
+
|[[#Ropeginterferon_alfa-2b_monotherapy_77|Ropeginterferon alfa-2b]]
 
| style="background-color:#eeee01" |Seems to have non-inferior composite endpoint
 
| style="background-color:#eeee01" |Seems to have non-inferior composite endpoint
 
|-
 
|-
 
|}
 
|}
−
====Immunotherapy====
+
''<sup>1</sup>Reported efficacy for FPSG is based on the 2011 update.''<br>
−
*[[Ropeginterferon alfa-2b (Besremi)]]
+
''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===
 
===References===
 +
# '''FPSG:''' Najean Y, Rain JD. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood. 1997 Nov 1;90(9):3370-7. [http://www.bloodjournal.org/content/90/9/3370.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/9345019 PubMed]
 +
## '''Update:''' Kiladjian JJ, Chevret S, Dosquet C, Chomienne C, Rain JD. Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980. J Clin Oncol. 2011 Oct 10;29(29):3907-13. Epub 2011 Sep 12. [https://doi.org/10.1200/JCO.2011.36.0792 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21911721 PubMed]
 +
# '''CYTO-PV:''' Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, De Stefano V, Elli E, Iurlo A, Latagliata R, Lunghi F, Lunghi M, Marfisi RM, Musto P, Masciulli A, Musolino C, Cascavilla N, Quarta G, Randi ML, Rapezzi D, Ruggeri M, Rumi E, Scortechini AR, Santini S, Scarano M, Siragusa S, Spadea A, Tieghi A, Angelucci E, Visani G, Vannucchi AM, Barbui T; CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013 Jan 3;368(1):22-33. Epub 2012 Dec 8. [https://doi.org/10.1056/nejmoa1208500 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23216616 PubMed] NCT01645124
 
# '''PROUD-PV:''' Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, Rossiev V, Dulicek P, Illes A, Pylypenko H, Sivcheva L, Mayer J, Yablokova V, Krejcy K, Grohmann-Izay B, Hasselbalch HC, Kralovics R, Kiladjian JJ; PROUD-PV Study Group. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020 Mar;7(3):e196-e208. Epub 2020 Jan 31. [https://doi.org/10.1016/s2352-3026(19)30236-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32014125 PubMed] NCT01949805
 
# '''PROUD-PV:''' Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, Rossiev V, Dulicek P, Illes A, Pylypenko H, Sivcheva L, Mayer J, Yablokova V, Krejcy K, Grohmann-Izay B, Hasselbalch HC, Kralovics R, Kiladjian JJ; PROUD-PV Study Group. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020 Mar;7(3):e196-e208. Epub 2020 Jan 31. [https://doi.org/10.1016/s2352-3026(19)30236-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32014125 PubMed] NCT01949805
 +
# '''MPD-RC 112:''' Mascarenhas J, Kosiorek HE, Prchal JT, Rambaldi A, Berenzon D, Yacoub A, Harrison CN, McMullin MF, Vannucchi AM, Ewing J, O'Connell CL, Kiladjian JJ, Mead AJ, Winton EF, Leibowitz DS, De Stefano V, Arcasoy MO, Kessler CM, Catchatourian R, Rondelli D, Silver RT, Bacigalupo A, Nagler A, Kremyanskaya M, Levine MF, Arango Ossa JE, McGovern E, Sandy L, Salama ME, Najfeld V, Tripodi J, Farnoud N, Penson AV, Weinberg RS, Price L, Goldberg JD, Barbui T, Marchioli R, Tognoni G, Rampal RK, Mesa RA, Dueck AC, Hoffman R. A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia. Blood. 2022 May 12;139(19):2931-2941. [https://doi.org/10.1182/blood.2021012743 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35007321/ PubMed] NCT01259856
  
 
==Placebo==
 
==Placebo==
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| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[#Aspirin_monotherapy|Aspirin]]
 
|[[#Aspirin_monotherapy|Aspirin]]
−
| style="background-color:#fc8d59" |Seems to have inferior combined outcome
+
| style="background-color:#91cf60" |Seems to have superior combined outcome
 
|-
 
|-
 
|}
 
|}
Line 99: Line 128:
 
===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://doi.org/10.1056/nejmoa035572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14711910 PubMed]
 
# '''ECLAP:''' Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. [https://doi.org/10.1056/nejmoa035572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14711910 PubMed]
−
 
−
==Hydroxyurea monotherapy {{#subobject:511984|Regimen=1}}==
 
−
 
−
===Regimen {{#subobject:84f020|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/90/9/3370.long Najean et al. 1997 (FPSG)]
 
−
|1980-NR
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#Pipobroman_monotherapy_88|Pipobroman]]
 
−
|style="background-color:#1a9850"|Superior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa1208500 Marchioli et al. 2012 (CYTO-PV)]
 
−
|2008-2012
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[#Hydroxyurea_monotherapy|Hydroxyurea]]; less strict hematocrit goal
 
−
|style="background-color:#1a9850"|Superior primary endpont
 
−
|-
 
−
|[https://doi.org/10.1182/blood.2021012743 Mascarenhas et al. 2022 (MPD-RC 112)]
 
−
|2011-2016
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Pegintereron_alfa-2a_monotherapy_99|Peginterferon alfa-2a]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CHR rate
 
−
|-
 
−
|[https://doi.org/10.1016/s2352-3026(19)30236-4 Gisslinger et al. 2020 (PROUD-PV)]
 
−
|2013-2015
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Ropeginterferon_alfa-2b_monotherapy_77|Ropeginterferon alfa-2b]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior composite endpoint
 
−
|-
 
−
|}
 
  
 
=Relapsed, refractory, or intolerant=
 
=Relapsed, refractory, or intolerant=

Revision as of 12:50, 31 December 2022

Back to Top

Section editor
Sanjay mohan.png
 Sanjay R. Mohan, MD, MSCI
Vanderbilt University
Nashville, TN
10 regimens on this page
11 variants on this page


Guidelines

ELN

ESMO

"How I Treat"

NCCN

First-line therapy

Aspirin monotherapy

Regimen

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

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 PubMed

Hydroxyurea monotherapy

Regimen

Study Years 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 endpont
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.
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. link to original article contains dosing details in manuscript PubMed NCT01259856

Placebo

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Landolfi et al. 2004 (ECLAP) 1998-2000 Phase 3 (C) Aspirin Seems to have superior combined outcome

No active treatment.

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 PubMed

Relapsed, refractory, or intolerant

Anagrelide monotherapy

Regimen

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

To be completed

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 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 PubMed

Hydroxyurea monotherapy

Regimen

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

The following is the approach recommended by Vannucchi in How I Treat (2014).

Chemotherapy

  • Hydroxyurea (Hydrea) 500 mg PO twice per day, with titration based on the target hematocrit and hematologic toxicity

Continued indefinitely

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 PubMed

Lenalidomide monotherapy

Regimen

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

To be completed

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 PubMed

Peginterferon alfa-2a monotherapy

Regimen variant #1, 45 mcg starting dose

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

Immunotherapy

  • Peginterferon alfa-2a (Pegasys) 45 mcg SC once per day on days 1, 8, 15, 22
    • Titrated up by 45 mcg every month in the absence of toxicity to goal dose of 180 mcg

28-day cycles

Regimen variant #2, 90 mcg starting dose

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

Quintás-Cardama et al. 2009 does not provide guidance on dose escalation or target dosing. Kiladjian et al. 2008 does not provide details on the dose escalation procedure.

Immunotherapy

  • Peginterferon alfa-2a (Pegasys) 90 mcg SC once per day on days 1, 8, 15, 22
    • Titrated up every two weeks in the absence of toxicity to 135 mcg SC once per day on days 1, 8, 15, 22
    • In the absence of hematologic response, dose increased to 180 mcg SC once per day on days 1, 8, 15, 22

Supportive therapy

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

28-day cycles

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

To be completed for historical reference

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 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 PubMed

Ruxolitinib monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Verstovsek et al. 2014 (INCB18424-256) 2008-NR Phase 2
Vannucchi et al. 2015 (RESPONSE) 2010-2013 Phase 3 (E-RT-switch-ooc) Standard therapy Superior disease control
Passamonti et al. 2016 (RESPONSE-2) 2014-2015 Phase 3b (E-switch-ooc) Standard therapy Superior disease control

There were several doses evaluated in INCB18424-256; the median total daily dose was 21.7 mg corresponding to approximately 10 mg PO twice per day. The most common comparator in RESPONSE and RESPONSE-2 was hydroxyurea.

Targeted therapy

Continued indefinitely

References

  1. INCB18424-256: Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rosen PJ, Rumi E, Gattoni E, Pieri L, Guglielmelli P, Elena C, He S, Contel N, Mookerjee B, Sandor V, Cazzola M, Kantarjian HM, Barbui T, Vannucchi AM. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 Inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. Cancer. 2014 Feb 15;120(4):513-20. 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 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 Years of enrollment Evidence Comparator Comparative Efficacy
Vannucchi et al. 2015 (RESPONSE) 2010-2013 Phase 3 (C) Ruxolitinib Inferior disease control

To be completed

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 PubMed

Response criteria

ELN

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