Essential thrombocythemia

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Last updated on 2024-07-23:8 regimens on this page
9 variants on this 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 link to PMC article EuroPMC
==ELN==
*2011: Barbui et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet EuroPMC
==ESMO==
*2015: Vannucchi et al. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Myeloproliferative Neoplasms.
=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)	Not reported 	Phase 3 (C) 	Anagrelide; prolonged release	Non-inferior mean platelet count
====Anticoagulation====
*Anagrelide (Agrylin) 0.5 mg PO twice per day
====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===
# 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01065038
# 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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 higher actuarial risk of arterial thrombosis (myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, or peripheral arterial thrombosis), venous thrombosis (deep-vein thrombosis, splanchnic-vein thrombosis, or pulmonary embolism), serious hemorrhage, or death from thrombotic or hemorrhagic causes (composite primary end point)(OR 0.64, 95% CI 0.42-0.96)
====Anticoagulation====
*Aspirin 75 mg (100 mg in Australia) PO once per day 
*Anagrelide (Agrylin) 0.5 mg PO twice per day
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===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 lower actuarial risk of arterial thrombosis (myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, or peripheral arterial thrombosis), venous thrombosis (deep-vein thrombosis, splanchnic-vein thrombosis, or pulmonary embolism), serious hemorrhage, or death from thrombotic or hemorrhagic causes (composite primary end point)(OR 1.57, 95% CI 1.04-2.37)
====Chemotherapy====
*Hydroxyurea (Hydrea) 500 to 1000 mg PO once per day
====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====
*Hydroxyurea (Hydrea) 1500 mg PO once per day
====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===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01065038
==Hydroxyurea monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cortelazzo et al. 1995	1990-1993 	Phase 3 (E-esc)	Observation	Higher thrombotic episode rate
====Chemotherapy====
*Hydroxyurea (Hydrea) 15 mg/kg/day PO
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===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==Peginterferon alfa-2a monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Quintás-Cardama et al. 2009 (MDACC DM03-0109)	2005-2009 	Phase 2
Note: This trial had several dose de-escalations due to toxicity and the dose here was the reported final starting dose.
====Immunotherapy====
*Peginterferon alfa-2a (Pegasys) 90 mcg SC once on day 1 (see titration instructions below)
7-day cycles
====Dose and schedule modifications====
*Peginterferon alfa-2a dose titrated up every two weeks in the absence of toxicity to 135 mcg
*In the absence of hematologic response, peginterferon alfa-2a dose increased to 180 mcg
===References===
# 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 dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC 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 EuroPMC
## 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 EuroPMC
=Relapsed, refractory, or intolerant to initial therapy=
==Anagrelide monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Awaiting publication (SURPASS ET)	2020 to not reported	Phase 3 (C)	Ropeginterferon alfa-2b	Not reported
====Anticoagulation====
*Anagrelide (Agrylin)
===References===
#SURPASS ET: NCT04285086
==Imetelstat monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Baerlocher et al. 2015 (CP14B015)	2010-01 to 2013-01 	Phase 2, less than 20 patients
====Targeted therapy====
*Imetelstat (Rytelo) 7.5 mg/kg or 9.4 mg/kg IV once on day 1
7-day cycles
===References===
# CP14B015: Baerlocher GM, Oppliger Leibundgut E, Ottmann OG, Spitzer G, Odenike O, McDevitt MA, Röth A, Daskalakis M, Burington B, Stuart M, Snyder DS. Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia. N Engl J Med. 2015 Sep 3;373(10):920-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01243073
==Peginterferon alfa-2a monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Verger et al. 2015	Not reported 	Observational
Note: Verger et al. 2015 do not specify a protocol but rather point to the European LeukemiaNet guidelines from 2011.
====Biomarker eligibility criteria====
*CALR mutation
====Immunotherapy====
*Peginterferon alfa-2a (Pegasys) 
===References===
# 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 EuroPMC
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==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===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC ISRCTN61925716
# 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00726232
=Response criteria=
==ELN==
*2009: Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference EuroPMC
Category:Essential thrombocythemia regimens
Category:Disease-specific pages
Category:Myeloproliferative neoplasms