Difference between revisions of "Essential thrombocythemia"
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Warner-admin (talk | contribs) m (Text replacement - "|Randomized Phase II" to "|Randomized Phase 2") |
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|NR | |NR | ||
|style="background-color:#1a9851"|Phase 3 (C) | |style="background-color:#1a9851"|Phase 3 (C) | ||
− | |A-PR | + | |[[#A-PR_88|A-PR]] |
|style="background-color:#eeee01"|Non-inferior mean platelet count | |style="background-color:#eeee01"|Non-inferior mean platelet count | ||
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!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |(SURPASS ET) | + | |Awaiting publication (SURPASS ET) |
|2020-NR | |2020-NR | ||
|style="background-color:#1a9851"|Phase 3 (C) | |style="background-color:#1a9851"|Phase 3 (C) | ||
− | |Ropeginterferon alfa-2b | + | |[[#Ropeginterferon_alfa-2b_77|Ropeginterferon alfa-2b]] |
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- |
Revision as of 15:31, 11 March 2022
Section editor | |
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Sanjay R. Mohan, MD, MSCI Vanderbilt University Nashville, TN |
8 regimens on this page
9 variants on this page
|
Guidelines
- 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
- 2015: Vannucchi et al. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
NCCN
First-line therapy
Anagrelide monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gisslinger et al. 2013 (ANAHYDRET) | 2002-2006 | Phase 3 (E-switch-ooc) | Hydroxyurea +/- Aspirin | Non-inferior composite endpoint |
Gisslinger et al. 2019 (TEAM-ET 2.0) | NR | Phase 3 (C) | A-PR | Non-inferior mean platelet count |
Anticoagulation
- Anagrelide (Agrylin) 0.5 mg PO twice per day
- ANAHYDRET: 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: Titrated to goal platelet count of 150 to 400 x 109/L
Supportive medications
- 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
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 contains verified protocol link to PMC article PubMed 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 contains verified protocol PubMed
Aspirin & Anagrelide
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Regimen
Study | Years 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
- Aspirin 75 mg (100 mg in Australia) PO once per day
- Anagrelide (Agrylin) 0.5 mg PO twice per day
- Doses were subsequently adjusted to maintain the platelet count at less than 400 x 109/L
Continued indefinitely
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 contains verified protocol PubMed content property of HemOnc.org
Aspirin & Hydroxyurea
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Regimen variant #1
Study | Years 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
- Hydroxyurea (Hydrea) 500 to 1000 mg PO once per day
- Doses were subsequently adjusted to maintain the platelet count at less than 400 x 109/L
Supportive medications
- Aspirin 75 mg (100 mg in Australia) PO once per day
Continued indefinitely
Regimen variant #2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gisslinger et al. 2013 (ANAHYDRET) | 2002-2006 | Phase 3 (E-switch-ooc) | Anagrelide +/- Aspirin | Non-inferior |
Chemotherapy
- Hydroxyurea (Hydrea) 1500 mg PO once per day
- 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)
Supportive medications
- 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
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 contains verified protocol PubMed
- 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 verified protocol link to PMC article PubMed NCT01065038
Hydroxyurea monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cortelazzo et al. 1995 | 1990-1993 | Phase 3 (E-esc) | Observation | Superior thrombotic episode rate |
Chemotherapy
- Hydroxyurea (Hydrea) 15 mg/kg/day PO
- 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 contains verified protocol PubMed
Observation
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Regimen
Study | Years 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
- 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 verified protocol PubMed
Peginterferon alfa-2a monotherapy
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Regimen
Study | Evidence |
---|---|
Quintás-Cardama et al. 2009 (MDACC DM03-0109) | Phase 2 |
This trial had several dose de-escalations due to toxicity and the dose here is the reported final starting dose.
Immunotherapy
- Peginterferon alfa-2a (Pegasys) 90 mcg SC once per day on days 1, 8, 15, 22
28-day cycles
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 contains protocol 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
Relapsed, refractory, or intolerant to initial therapy
Anagrelide monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (SURPASS ET) | 2020-NR | Phase 3 (C) | Ropeginterferon alfa-2b | Not reported |
Anticoagulation
References
- SURPASS ET: NCT04285086
Peginterferon alfa-2a monotherapy
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Regimen
Study | Evidence |
---|---|
Verger et al. 2015 | Observational |
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
- 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 protocol PubMed
Ruxolitinib monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Verstovsek et al. 2017 (INCB 18424-256) | 2008-2009 | 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: Harrison et al. 2017 does not specify a starting dose.
Targeted therapy
- Ruxolitinib (Jakafi) as follows:
- Starting dose: 25 mg PO twice per day
- Titrate to keep platelets less than 400 x 109/L
Continued indefinitely
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 PubMed ISRCTN61925716
- INCB 18424-256: 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 verified protocol PubMed