Essential thrombocythemia

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Section editor
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 Sanjay R. Mohan, MD, MSCI
Vanderbilt University
Nashville, TN, USA
8 regimens on this page
9 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.

  • Tefferi A, Vannucchi AM, Barbui T. Essential thrombocythemia treatment algorithm 2018. Blood Cancer J. 2018 Jan 10;8(1):2. link to original article PubMed

ELN

ESMO

NCCN

First-line therapy

Anagrelide monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gisslinger et al. 2013 (ANAHYDRET) 2002-2006 Phase 3 (E-switch-ooc) Hydroxyurea +/- Aspirin Non-inferior composite primary endpoint
Gisslinger et al. 2019 (TEAM-ET 2.0) NR Phase 3 (C) Anagrelide; prolonged release Non-inferior mean platelet count

Anticoagulation

Supportive therapy

  • ANAHYDRET: Neither aspirin nor Clopidogrel (Plavix) were required in the study, but patients who were already taking either drug for at least two weeks were allowed to continue taking it during the study per investigator discretion

Continued indefinitely

Dose and schedule modifications

  • ANAHYDRET: Anagrelide (Agrylin) increased until maintenance of the platelet count at normal (less than or equal to 450 x 109/L) or close to normal levels (450 to 600 x 109/L)
  • TEAM-ET 2.0: Anagrelide (Agrylin) titrated to goal platelet count of 150 to 400 x 109/L

References

  1. ANAHYDRET: Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, Kralovics R, Petrides PE; ANAHYDRET Study Group. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013 Mar 7;121(10):1720-8. Epub 2013 Jan 11. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01065038
  2. TEAM-ET 2.0: Gisslinger H, Buxhofer-Ausch V, Hodisch J, Radinoff A, Karyagina E, Kyrcz-Krzemień S, Abdulkadyrov K, Gerbutavicius R, Melikyan A, Burgstaller S, Hus M, Kłoczko J, Yablokova V, Tzvetkov N, Całbecka M, Shneyder T, Warzocha K, Jurgutis M, Kaplanov K, Jilma B, Schoergenhofer C, Klade C. A phase III randomized, multicentre, double blind, active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia - the TEAM-ET 2·0 trial. Br J Haematol. 2019 May;185(4):691-700. Epub 2019 Mar 28. link to original article contains dosing details in manuscript link to PMC article PubMed EudraCT 2013‐003410‐41

Aspirin & Anagrelide

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Harrison et al. 2005 (UK MRC PT-1) 1997-2002 Phase 3 (E-switch-ooc) Aspirin & Hydroxyurea Seems to have inferior composite primary end point

Anticoagulation

Continued indefinitely

Dose and schedule modifications

  • Anagrelide (Agrylin) doses were subsequently adjusted to maintain the platelet count at less than 400 x 109/L

References

  1. UK MRC PT-1: Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org

Aspirin & Hydroxyurea

Regimen variant #1

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Harrison et al. 2005 (UK MRC PT-1) 1997-2002 Phase 3 (C) Aspirin & Anagrelide Seems to have superior composite primary end point

Chemotherapy

Supportive therapy

  • Aspirin 75 mg (100 mg in Australia) PO once per day

Continued indefinitely

Dose and schedule modifications

  • Hydroxyurea (Hydrea) doses were subsequently adjusted to maintain the platelet count at less than 400 x 109/L


Regimen variant #2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gisslinger et al. 2013 (ANAHYDRET) 2002-2006 Phase 3 (E-switch-ooc) Anagrelide +/- Aspirin Non-inferior composite primary endpoint

Chemotherapy

Supportive therapy

  • Neither aspirin nor Clopidogrel (Plavix) were required in the study, but patients who were already taking either drug for at least two weeks were allowed to continue taking it during the study per investigator discretion

Continued indefinitely

Dose and schedule modifications

  • Hydroxyurea (Hydrea) increased until maintenance of the platelet count at normal (less than or equal to 450 x 109/L) or close to normal levels (450 to 600 x 109/L)

References

  1. UK MRC PT-1: Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45. link to original article contains dosing details in manuscript PubMed
  2. ANAHYDRET: Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, Kralovics R, Petrides PE; ANAHYDRET Study Group. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013 Mar 7;121(10):1720-8. Epub 2013 Jan 11. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01065038

Hydroxyurea monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Cortelazzo et al. 1995 1990-1993 Phase 3 (E-esc) Observation Superior thrombotic episode rate

Chemotherapy

Continued indefinitely

Dose and schedule modifications

  • Hydroxyurea (Hydrea) doses were subsequently adjusted to maintain the platelet count at less than 600 x 109/L without lowering the WBC count below 4 x 109/L

References

  1. Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, Barbui T. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995 Apr 27;332(17):1132-6. link to original article contains dosing details in manuscript PubMed

Observation

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Cortelazzo et al. 1995 1990-1993 Phase 3 (C) Hydroxyurea Inferior thrombotic episode rate

No active antineoplastic treatment; used as a comparator arm.

References

  1. Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, Barbui T. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995 Apr 27;332(17):1132-6. link to original article contains dosing details in manuscript PubMed

Peginterferon alfa-2a monotherapy

Regimen

Study Evidence
Quintás-Cardama et al. 2009 (MDACC DM03-0109) Phase 2

Note: This trial had several dose de-escalations due to toxicity and the dose here is the reported final starting dose.

Immunotherapy

7-day cycles

References

  1. 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

Relapsed, refractory, or intolerant to initial therapy

Anagrelide monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Awaiting publication (SURPASS ET) 2020-NR Phase 3 (C) Ropeginterferon alfa-2b Not reported

Anticoagulation

References

  1. SURPASS ET: NCT04285086

Peginterferon alfa-2a monotherapy

Regimen

Study Evidence
Verger et al. 2015 Observational

Note: Verger et al. 2015 do not specify a protocol but rather point to the European LeukemiaNet guidelines from 2011. All patients in this study had CALR mutations.

Immunotherapy

References

  1. Verger E, Cassinat B, Chauveau A, Dosquet C, Giraudier S, Schlageter MH, Ianotto JC, Yassin MA, Al-Dewik N, Carillo S, Legouffe E, Ugo V, Chomienne C, Kiladjian JJ. Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations. Blood. 2015 Dec 10;126(24):2585-91. Epub 2015 Oct 20. link to original article does not contain dosing details PubMed

Ruxolitinib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Verstovsek et al. 2017 (INCB 18424-256ET) 2008-07 to 2009-04 Phase 2
Harrison et al. 2017 (MAJIC-ET) 2012-2015 Randomized Phase 2 (E-switch-ooc) "Best available therapy" Did not meet primary endpoint of CR rate

Note: recommended doses are starting doses.

Targeted therapy

  • Ruxolitinib (Jakafi) by the following laboratory-based criteria:
    • Platelets between 100 to 200 x 109/L: 20 mg PO twice per day
    • Platelets greater than 200 x 109/L: 25 mg PO twice per day

Supportive therapy

  • Aspirin 75 mg PO once per day was advised unless contraindicated (MAJIC-ET)

Continued indefinitely

Dose and schedule modifications

  • INCB 18424-256ET: titrate to keep platelets less than 400 x 109/L

References

  1. MAJIC-ET: Harrison CN, Mead AJ, Panchal A, Fox S, Yap C, Gbandi E, Houlton A, Alimam S, Ewing J, Wood M, Chen F, Coppell J, Panoskaltsis N, Knapper S, Ali S, Hamblin A, Scherber R, Dueck AC, Cross NCP, Mesa R, McMullin MF. Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide. Blood. 2017 Oct 26;130(17):1889-1897. Epub 2017 Aug 9. link to original article link to PMC article contains dosing details in manuscript PubMed ISRCTN61925716
  2. INCB 18424-256ET: Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rumi E, Gattoni E, Pieri L, Zhen H, Granier M, Assad A, Cazzola M, Kantarjian HM, Barbui T, Vannucchi AM. Ruxolitinib for essential thrombocythemia refractory to or intolerant of hydroxyurea: long-term phase 2 study results. Blood. 2017 Oct 12;130(15):1768-1771. Epub 2017 Aug 21. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00726232

Response criteria

ELN

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