Polycythemia vera

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 Sanjay R. Mohan, MD, MSCI
Nashville, TN
10 regimens on this page
11 variants on this page


Guidelines

ELN

ESMO

"How I Treat"

NCCN

First-line therapy

Aspirin monotherapy

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Regimen

Study Evidence Comparator Efficacy
Landolfi et al. 2004 (ECLAP) Phase III (E) 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. PubMed

Hydroxyurea monotherapy

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Regimen

Study Evidence Comparator Efficacy
Najean et al. 1997 (FPSG) Phase III (E) Pipobroman Superior OS (*)
Marchioli et al. 2012 (CYTO-PV) Phase III (E) Less strict hematocrit goal Superior primary endpont

The following is the approach recommended by Vannucchi in How I Treat (2014). Reported efficacy for FPSG is based on the 2011 update.

Chemotherapy

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

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

Placebo

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Regimen

Study Evidence Comparator Efficacy
Landolfi et al. 2004 (ECLAP) Phase III (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. PubMed

Relapsed, refractory, or intolerant

Anagrelide monotherapy

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Regimen

Study Evidence Comparator Efficacy
Vannucchi et al. 2015 (RESPONSE) Phase III (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 verified protocol link to PMC article PubMed
    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

Hydroxyurea monotherapy

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Regimen

Study Evidence Comparator Efficacy
Vannucchi et al. 2015 (RESPONSE) Phase III (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 verified protocol link to PMC article PubMed
    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

Interferon monotherapy

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Regimen

Study Evidence Comparator Efficacy
Vannucchi et al. 2015 (RESPONSE) Phase III (C) Ruxolitinib Inferior disease control

To be completed; RESPONSE does not specify what type of interferon was used in this arm.

Immunotherapy

  • Interferon

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 verified protocol link to PMC article PubMed
    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

Lenalidomide monotherapy

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Regimen

Study Evidence Comparator Efficacy
Vannucchi et al. 2015 (RESPONSE) Phase III (C) Ruxolitinib Inferior disease control

To be completed

Chemotherapy

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 verified protocol link to PMC article PubMed
    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

Peginterferon alfa-2a monotherapy

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Regimen

Study Evidence
Kiladjian et al. 2008 (PVN1) Phase II
Quintás-Cardama et al. 2009 Phase II

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

Immunotherapy

  • Peginterferon alfa-2a (Pegasys) 90 mcg SC once per week, titrated up every two weeks in the absence of toxicity to 135 mcg SC once per week
    • In the absence of hematologic response, dose increased to 180 mcg SC once per week

Supportive medications

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

Unspecified duration

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 verified protocol PubMed
  2. 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 protocol link to PMC article PubMed
    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

Pipobroman monotherapy

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Regimen

Study Evidence Comparator Efficacy
Vannucchi et al. 2015 (RESPONSE) Phase III (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 verified protocol link to PMC article PubMed
    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

Ruxolitinib monotherapy

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Regimen

Study Evidence Comparator Efficacy
Verstovsek et al. 2014 Phase II
Vannucchi et al. 2015 (RESPONSE) Phase III (E) Standard therapy Superior disease control
Passamonti et al. 2016 (RESPONSE-2) Phase III (E) Standard therapy Superior disease control

There were several doses evaluated in Verstovsek et al. 2014; the median total daily dose was 21.7 mg corresponding to approximately 10 mg PO twice per day. The most common comparator in RESPONSE and RESPONSE-2 was hydroxyurea.

Chemotherapy

Continued indefinitely

References

  1. 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 verified protocol link to PMC article PubMed content property of HemOnc.org
  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 verified protocol link to PMC article PubMed
    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
  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 protocol PubMed

Thalidomide monotherapy

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Regimen

Study Evidence Comparator Efficacy
Vannucchi et al. 2015 (RESPONSE) Phase III (C) Ruxolitinib Inferior disease control

To be completed

Chemotherapy

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 verified protocol link to PMC article PubMed
    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

Response criteria

ELN

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