Difference between revisions of "Myelofibrosis"

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!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187954/ Verstovsek et al. 2010]
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187954/ Verstovsek et al. 2010 (INCB 18424-251)]
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|2007-NR
 
|style="background-color:#91cf61"|Phase II
 
|style="background-color:#91cf61"|Phase II
 
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|[https://www.nejm.org/doi/full/10.1056/NEJMoa1110556 Harrison et al. 2012 (COMFORT-II)]
 
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1110556 Harrison et al. 2012 (COMFORT-II)]
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|2009-2010
 
|style="background-color:#1a9851"|Phase III (E-RT-switch-ooc)
 
|style="background-color:#1a9851"|Phase III (E-RT-switch-ooc)
 
|"Best available therapy"
 
|"Best available therapy"
 
|style="background-color:#91cf60"|Seems to have superior OS
 
|style="background-color:#91cf60"|Seems to have superior OS
 
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|-
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|[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13379/full Mead et al. 2015 (ROBUST)]
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5060023/ Al-Ali et al. 2016 (JUMP)]
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|2011-2014
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|style="background-color:#91cf61"|Phase II
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|style="background-color:#91cf61"|Phase 3b
 
|style="background-color:#d3d3d3"|
 
|style="background-color:#d3d3d3"|
 
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|style="background-color:#d3d3d3"|
 
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5060023/ Al-Ali et al. 2016 (JUMP)]
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|[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13379/full Mead et al. 2015 (ROBUST)]
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|{{#subobject:xx|ToDo=1}}
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|2012-NR
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|style="background-color:#91cf61"|Phase 3b
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|style="background-color:#91cf61"|Phase II
 
|style="background-color:#d3d3d3"|
 
|style="background-color:#d3d3d3"|
 
|style="background-color:#d3d3d3"|
 
|style="background-color:#d3d3d3"|
 
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|[https://doi.org/10.1200/JCO.2017.73.4418 Mesa et al. 2017 (SIMPLIFY-1)]
 
|[https://doi.org/10.1200/JCO.2017.73.4418 Mesa et al. 2017 (SIMPLIFY-1)]
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|2013-2016
 
|style="background-color:#1a9851"|Phase III (C)
 
|style="background-color:#1a9851"|Phase III (C)
 
|Momelotinib
 
|Momelotinib
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|[https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30237-5/fulltext Harrison et al. 2017 (SIMPLIFY-2)]
 
|[https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30237-5/fulltext Harrison et al. 2017 (SIMPLIFY-2)]
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|{{#subobject:xx|ToDo=1}}
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|2014-2016
 
|style="background-color:#1a9851"|Phase III (C)
 
|style="background-color:#1a9851"|Phase III (C)
 
|Momelotinib
 
|Momelotinib
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|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885169/ Mascarenhas et al. 2018 (PERSIST-2)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885169/ Mascarenhas et al. 2018 (PERSIST-2)]
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|{{#subobject:xx|ToDo=1}}
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|2014-2016
 
|style="background-color:#1a9851"|Phase III (C)
 
|style="background-color:#1a9851"|Phase III (C)
 
|Pacritinib
 
|Pacritinib
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===References===
 
===References===
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# '''SIMPLIFY-1:''' Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, Estrov Z, Fridman JS, Bradley EC, Erickson-Viitanen S, Vaddi K, Levy R, Tefferi A. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010 Sep 16;363(12):1117-27. [https://www.nejm.org/doi/full/10.1056/NEJMoa1002028 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1002028/suppl_file/nejmoa1002028_appendix.pdf supplementary appendix] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187954/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20843246 PubMed]
+
# '''INCB 18424-251:''' Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, Estrov Z, Fridman JS, Bradley EC, Erickson-Viitanen S, Vaddi K, Levy R, Tefferi A. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010 Sep 16;363(12):1117-27. [https://www.nejm.org/doi/full/10.1056/NEJMoa1002028 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1002028/suppl_file/nejmoa1002028_appendix.pdf supplementary appendix] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187954/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20843246 PubMed] NCT00509899
 
# '''COMFORT-I:''' Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Koumenis IL, Sun W, Sandor V, Kantarjian HM. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):799-807. [https://www.nejm.org/doi/full/10.1056/NEJMoa1110557 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1110557/suppl_file/nejmoa1110557_appendix.pdf supplementary appendix] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1110557/suppl_file/nejmoa1110557_protocol.pdf trial protocol] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822164/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22375971 PubMed]
 
# '''COMFORT-I:''' Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Koumenis IL, Sun W, Sandor V, Kantarjian HM. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):799-807. [https://www.nejm.org/doi/full/10.1056/NEJMoa1110557 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1110557/suppl_file/nejmoa1110557_appendix.pdf supplementary appendix] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1110557/suppl_file/nejmoa1110557_protocol.pdf trial protocol] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822164/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22375971 PubMed]
 
## '''Update:''' Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH, Arcasoy MO, Hexner EO, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Sun W, Sandor V, Kantarjian HM. Efficacy, safety and survival with ruxolitinib treatment in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I. Haematologica. 2013 Dec;98(12):1865-71. Epub 2013 Sep 13. [http://www.haematologica.org/content/98/12/1865.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856961/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24038026 PubMed]
 
## '''Update:''' Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH, Arcasoy MO, Hexner EO, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Sun W, Sandor V, Kantarjian HM. Efficacy, safety and survival with ruxolitinib treatment in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I. Haematologica. 2013 Dec;98(12):1865-71. Epub 2013 Sep 13. [http://www.haematologica.org/content/98/12/1865.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856961/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24038026 PubMed]
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## '''Pooled update:''' Vannucchi AM, Kantarjian HM, Kiladjian JJ, Gotlib J, Cervantes F, Mesa RA, Sarlis NJ, Peng W, Sandor V, Gopalakrishna P, Hmissi A, Stalbovskaya V, Gupta V, Harrison C, Verstovsek S; COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015 Sep;100(9):1139-45. Epub 2015 Jun 11. [http://www.haematologica.org/content/100/9/1139.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800694/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26069290 PubMed]
 
## '''Pooled update:''' Vannucchi AM, Kantarjian HM, Kiladjian JJ, Gotlib J, Cervantes F, Mesa RA, Sarlis NJ, Peng W, Sandor V, Gopalakrishna P, Hmissi A, Stalbovskaya V, Gupta V, Harrison C, Verstovsek S; COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015 Sep;100(9):1139-45. Epub 2015 Jun 11. [http://www.haematologica.org/content/100/9/1139.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800694/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26069290 PubMed]
 
## '''Update:''' Verstovsek S, Mesa RA, Gotlib J, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner EO, Lyons RM, Paquette R, Raza A, Jones M, Kornacki D, Sun K, Kantarjian H; COMFORT-I investigators. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial. J Hematol Oncol. 2017 Feb 22;10(1):55. [https://jhoonline.biomedcentral.com/articles/10.1186/s13045-017-0417-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322633/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28228106 PubMed]
 
## '''Update:''' Verstovsek S, Mesa RA, Gotlib J, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner EO, Lyons RM, Paquette R, Raza A, Jones M, Kornacki D, Sun K, Kantarjian H; COMFORT-I investigators. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial. J Hematol Oncol. 2017 Feb 22;10(1):55. [https://jhoonline.biomedcentral.com/articles/10.1186/s13045-017-0417-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322633/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28228106 PubMed]
−
# '''COMFORT-II:''' Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):787-98. [https://www.nejm.org/doi/full/10.1056/NEJMoa1110556 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/22375970 PubMed] content property of [http://hemonc.org HemOnc.org]
+
# '''COMFORT-II:''' Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):787-98. [https://www.nejm.org/doi/full/10.1056/NEJMoa1110556 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/22375970 PubMed] content property of [http://hemonc.org HemOnc.org] NCT00934544
 
## '''Update:''' Cervantes F, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Sirulnik A, Stalbovskaya V, McQuitty M, Hunter DS, Levy RS, Passamonti F, Barbui T, Barosi G, Harrison CN, Knoops L, Gisslinger H. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013 Dec 12;122(25):4047-53. Epub 2013 Oct 30. Erratum in: Blood. 2016 Dec 22;128(25):3013. [http://www.bloodjournal.org/content/122/25/4047.full link to original article] [https://pubmed.ncbi.nlm.nih.gov/24174625 PubMed]
 
## '''Update:''' Cervantes F, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Sirulnik A, Stalbovskaya V, McQuitty M, Hunter DS, Levy RS, Passamonti F, Barbui T, Barosi G, Harrison CN, Knoops L, Gisslinger H. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013 Dec 12;122(25):4047-53. Epub 2013 Oct 30. Erratum in: Blood. 2016 Dec 22;128(25):3013. [http://www.bloodjournal.org/content/122/25/4047.full link to original article] [https://pubmed.ncbi.nlm.nih.gov/24174625 PubMed]
 
## '''Pooled update:''' Vannucchi AM, Kantarjian HM, Kiladjian JJ, Gotlib J, Cervantes F, Mesa RA, Sarlis NJ, Peng W, Sandor V, Gopalakrishna P, Hmissi A, Stalbovskaya V, Gupta V, Harrison C, Verstovsek S; COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015 Sep;100(9):1139-45. Epub 2015 Jun 11. [http://www.haematologica.org/content/100/9/1139.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800694/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26069290 PubMed]
 
## '''Pooled update:''' Vannucchi AM, Kantarjian HM, Kiladjian JJ, Gotlib J, Cervantes F, Mesa RA, Sarlis NJ, Peng W, Sandor V, Gopalakrishna P, Hmissi A, Stalbovskaya V, Gupta V, Harrison C, Verstovsek S; COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015 Sep;100(9):1139-45. Epub 2015 Jun 11. [http://www.haematologica.org/content/100/9/1139.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800694/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26069290 PubMed]
 
## '''Update:''' Harrison CN, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Gisslinger H, Knoops L, Cervantes F, Jones MM, Sun K, McQuitty M, Stalbovskaya V, Gopalakrishna P, Barbui T. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016 Aug;30(8):1701-7. Epub 2016 May 23. [https://doi.org/10.1038/leu.2016.148 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399157/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27211272 PubMed]
 
## '''Update:''' Harrison CN, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Gisslinger H, Knoops L, Cervantes F, Jones MM, Sun K, McQuitty M, Stalbovskaya V, Gopalakrishna P, Barbui T. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016 Aug;30(8):1701-7. Epub 2016 May 23. [https://doi.org/10.1038/leu.2016.148 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399157/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27211272 PubMed]
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# '''ROBUST:''' Mead AJ, Milojkovic D, Knapper S, Garg M, Chacko J, Farquharson M, Yin J, Ali S, Clark RE, Andrews C, Ktiouet Dawson M, Harrison C. Response to ruxolitinib in patients with intermediate-1-, intermediate-2-, and high-risk myelofibrosis: results of the UK ROBUST Trial. Br J Haematol. 2015 Jul;170(1):29-39. Epub 2015 Mar 30. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13379/full link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/25824940 PubMed]
+
# '''ROBUST:''' Mead AJ, Milojkovic D, Knapper S, Garg M, Chacko J, Farquharson M, Yin J, Ali S, Clark RE, Andrews C, Ktiouet Dawson M, Harrison C. Response to ruxolitinib in patients with intermediate-1-, intermediate-2-, and high-risk myelofibrosis: results of the UK ROBUST Trial. Br J Haematol. 2015 Jul;170(1):29-39. Epub 2015 Mar 30. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13379/full link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/25824940 PubMed] NCT01558739
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# '''JUMP:''' Al-Ali HK, Griesshammer M, le Coutre P, Waller CF, Liberati AM, Schafhausen P, Tavares R, Giraldo P, Foltz L, Raanani P, Gupta V, Tannir B, Ronco JP, Ghosh J, Martino B, Vannucchi AM. Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial. Haematologica. 2016 Sep;101(9):1065-73. Epub 2016 May 31. [http://www.haematologica.org/content/101/9/1065.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5060023/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27247324 PubMed]
+
# '''JUMP:''' Al-Ali HK, Griesshammer M, le Coutre P, Waller CF, Liberati AM, Schafhausen P, Tavares R, Giraldo P, Foltz L, Raanani P, Gupta V, Tannir B, Ronco JP, Ghosh J, Martino B, Vannucchi AM. Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial. Haematologica. 2016 Sep;101(9):1065-73. Epub 2016 May 31. [http://www.haematologica.org/content/101/9/1065.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5060023/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27247324 PubMed] NCT01493414
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# '''SIMPLIFY-1:''' Mesa RA, Kiladjian JJ, Catalano JV, Devos T, Egyed M, Hellmann A, McLornan D, Shimoda K, Winton EF, Deng W, Dubowy RL, Maltzman JD, Cervantes F, Gotlib J. SIMPLIFY-1: a phase III randomized trial of momelotinib versus ruxolitinib in Janus kinase inhibitor-naïve patients with myelofibrosis. J Clin Oncol. 2017 Dec 1;35(34):3844-3850. Epub 2017 Sep 20. [https://doi.org/10.1200/JCO.2017.73.4418 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28930494 PubMed]
+
# '''SIMPLIFY-1:''' Mesa RA, Kiladjian JJ, Catalano JV, Devos T, Egyed M, Hellmann A, McLornan D, Shimoda K, Winton EF, Deng W, Dubowy RL, Maltzman JD, Cervantes F, Gotlib J. SIMPLIFY-1: a phase III randomized trial of momelotinib versus ruxolitinib in Janus kinase inhibitor-naïve patients with myelofibrosis. J Clin Oncol. 2017 Dec 1;35(34):3844-3850. Epub 2017 Sep 20. [https://doi.org/10.1200/JCO.2017.73.4418 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28930494 PubMed] NCT01969838
−
# '''SIMPLIFY 2:''' Harrison CN, Vannucchi AM, Platzbecker U, Cervantes F, Gupta V, Lavie D, Passamonti F, Winton EF, Dong H, Kawashima J, Maltzman JD, Kiladjian JJ, Verstovsek S. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol. 2018 Feb;5(2):e73-e81. Epub 2017 Dec 20. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30237-5/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/29275119 PubMed]
+
# '''SIMPLIFY-2:''' Harrison CN, Vannucchi AM, Platzbecker U, Cervantes F, Gupta V, Lavie D, Passamonti F, Winton EF, Dong H, Kawashima J, Maltzman JD, Kiladjian JJ, Verstovsek S. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol. 2018 Feb;5(2):e73-e81. Epub 2017 Dec 20. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30237-5/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/29275119 PubMed] NCT02101268
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# '''PERSIST-2:''' Mascarenhas J, Hoffman R, Talpaz M, Gerds AT, Stein B, Gupta V, Szoke A, Drummond M, Pristupa A, Granston T, Daly R, Al-Fayoumi S, Callahan JA, Singer JW, Gotlib J, Jamieson C, Harrison C, Mesa R, Verstovsek S. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018 May 1;4(5):652-659. Epub 2018 Mar 8. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2674384 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885169/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29522138 PubMed]
+
# '''PERSIST-2:''' Mascarenhas J, Hoffman R, Talpaz M, Gerds AT, Stein B, Gupta V, Szoke A, Drummond M, Pristupa A, Granston T, Daly R, Al-Fayoumi S, Callahan JA, Singer JW, Gotlib J, Jamieson C, Harrison C, Mesa R, Verstovsek S. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018 May 1;4(5):652-659. Epub 2018 Mar 8. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2674384 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885169/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29522138 PubMed] NCT02055781
  
 
=Investigational agents=
 
=Investigational agents=

Revision as of 00:33, 20 September 2020

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


Guidelines

ESMO

NCCN

All lines of therapy

Fedratinib monotherapy

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Regimen

FDA-recommended dose
Study Years of enrollment Evidence Comparator Comparative Efficacy
Pardanani et al. 2015 (JAKARTA) 2011-2012 Phase III (E-RT-esc) Fedratinib; 500 mg/d Not reported
Placebo Superior RR

Targeted therapy

28-day cycles

References

  1. JAKARTA: Pardanani A, Harrison C, Cortes JE, Cervantes F, Mesa RA, Milligan D, Masszi T, Mishchenko E, Jourdan E, Vannucchi AM, Drummond MW, Jurgutis M, Kuliczkowski K, Gheorghita E, Passamonti F, Neumann F, Patki A, Gao G, Tefferi A. Safety and efficacy of fedratinib in patients with primary or secondary myelofibrosis: A randomized clinical trial. JAMA Oncol. 2015 Aug 1;1(5):643-51. link to original article contains verified protocol PubMed

Hydroxyurea monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Mesa et al. 2017 (PERSIST-1) Phase III (C) Pacritinib Inferior spleen volume reduction

Note: this was the most commonly used "best available therapy" (BAT) in PERSIST-1.

Chemotherapy

References

  1. PERSIST-1: Mesa RA, Vannucchi AM, Mead A, Egyed M, Szoke A, Suvorov A, Jakucs J, Perkins A, Prasad R, Mayer J, Demeter J, Ganly P, Singer JW, Zhou H, Dean JP, Te Boekhorst PA, Nangalia J, Kiladjian JJ, Harrison CN. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Haematol. 2017 May;4(5):e225-e236. Epub 2017 Mar 20. link to original article PubMed

Lenalidomide monotherapy

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Regimen

Study Evidence
Tefferi et al. 2006 Phase II

Targeted therapy

References

  1. Tefferi A, Cortes J, Verstovsek S, Mesa RA, Thomas D, Lasho TL, Hogan WJ, Litzow MR, Allred JB, Jones D, Byrne C, Zeldis JB, Ketterling RP, McClure RF, Giles F, Kantarjian HM. Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood. 2006 Aug 15;108(4):1158-64. Epub 2006 Apr 11. link to original article contains protocol PubMed

Pomalidomide monotherapy

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Regimen variant #1

Study Years of enrollment Evidence Comparator Comparative Efficacy
Begna et al. 2010 (PO-MMM-PI-0007) NR Phase II
Tefferi et al. 2016 (RESUME) 2010-2012 Phase III (E-esc) Placebo Did not meet primary endpoint of RBC-transfusion independence within 6 mo

Targeted therapy

  • Pomalidomide (Pomalyst) 0.5 mg PO once per day
    • In PO-MMM-PI-0007, escalation up to 2 mg PO once per day allowed after first six cycles

28-day cycles

Regimen variant #2

Study Evidence Comparator Comparative Efficacy
Tefferi et al. 2009 (CC-4047-MMM-001) Randomized Phase II (E-esc) 1. Pomalidomide (2 mg/d) & Prednisone
2. Pomalidomide (0.5 mg/d) & Prednisone
3. Prednisone 		Not reported

Targeted therapy

28-day cycles

References

  1. CC-4047-MMM-001: Tefferi A, Verstovsek S, Barosi G, Passamonti F, Roboz GJ, Gisslinger H, Paquette RL, Cervantes F, Rivera CE, Deeg HJ, Thiele J, Kvasnicka HM, Vardiman JW, Zhang Y, Bekele BN, Mesa RA, Gale RP, Kantarjian HM. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol. 2009 Sep 20;27(27):4563-9. Epub 2009 Aug 3. link to original article link to PMC article PubMed
  2. PO-MMM-PI-0007: Begna KH, Mesa RA, Pardanani A, Hogan WJ, Litzow MR, McClure RF, Tefferi A. A phase-2 trial of low-dose pomalidomide in myelofibrosis. Leukemia. 2011 Feb;25(2):301-4. Epub 2010 Nov 5. trial protocol contains verified protocol PubMed
  3. RESUME: Tefferi A, Al-Ali HK, Barosi G, Devos T, Gisslinger H, Jiang Q, Kiladjian JJ, Mesa R, Passamonti F, McMullin MF, Ribrag V, Schiller G, Vannucchi AM, Zhou D, Reiser D, Zhong J, Gale RP. A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence. Leukemia. 2017 Apr;31(4):896-902. Epub 2016 Oct 24. link to original article contains verified protocol link to PMC article PubMed NCT01178281

Pomalidomide & Prednisone

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Regimen variant #1

Study Evidence Comparator Comparative Efficacy
Tefferi et al. 2009 (CC-4047-MMM-001) Randomized Phase II, <20 in this arm (E-esc) 1. Pomalidomide
2. Pomalidomide (0.5 mg/d) & Prednisone
3. Prednisone 		Not reported

Targeted therapy

Chemotherapy

  • Prednisone (Sterapred) as follows:
    • Cycle 1: 30 mg PO once per day
    • Cycle 2: 15 mg PO once per day
    • Cycle 3: 15 mg PO every other day

28-day cycles

Regimen variant #2

Study Evidence Comparator Comparative Efficacy
Tefferi et al. 2009 (CC-4047-MMM-001) Randomized Phase II (E-esc) 1. Pomalidomide
2. Pomalidomide (2 mg/d) & Prednisone
3. Prednisone 		Not reported

Targeted therapy

Chemotherapy

  • Prednisone (Sterapred) as follows:
    • Cycle 1: 30 mg PO once per day
    • Cycle 2: 15 mg PO once per day
    • Cycle 3: 15 mg PO every other day

28-day cycles

References

  1. CC-4047-MMM-001: Tefferi A, Verstovsek S, Barosi G, Passamonti F, Roboz GJ, Gisslinger H, Paquette RL, Cervantes F, Rivera CE, Deeg HJ, Thiele J, Kvasnicka HM, Vardiman JW, Zhang Y, Bekele BN, Mesa RA, Gale RP, Kantarjian HM. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol. 2009 Sep 20;27(27):4563-9. Epub 2009 Aug 3. link to original article link to PMC article PubMed

Prednisone monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Tefferi et al. 2009 (CC-4047-MMM-001) Randomized Phase II (C) 1. Pomalidomide
2. Pomalidomide (2 mg/d) & Prednisone
3. Pomalidomide (0.5 mg/d) & Prednisone 		Not reported

Chemotherapy

  • Prednisone (Sterapred) as follows:
    • Cycle 1: 30 mg PO once per day
    • Cycle 2: 15 mg PO once per day
    • Cycle 3: 15 mg PO every other day

28-day cycle for 3 cycles

References

  1. CC-4047-MMM-001: Tefferi A, Verstovsek S, Barosi G, Passamonti F, Roboz GJ, Gisslinger H, Paquette RL, Cervantes F, Rivera CE, Deeg HJ, Thiele J, Kvasnicka HM, Vardiman JW, Zhang Y, Bekele BN, Mesa RA, Gale RP, Kantarjian HM. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol. 2009 Sep 20;27(27):4563-9. Epub 2009 Aug 3. link to original article link to PMC article PubMed

Ruxolitinib monotherapy

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Regimen

COMFORT: COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Treatment

Study Years of enrollment Evidence Comparator Comparative Efficacy
Verstovsek et al. 2010 (INCB 18424-251) 2007-NR Phase II
Verstovsek et al. 2012 (COMFORT-I) 2009-2010 Phase III (E-RT-esc) Placebo Seems to have superior OS (*)
Harrison et al. 2012 (COMFORT-II) 2009-2010 Phase III (E-RT-switch-ooc) "Best available therapy" Seems to have superior OS
Al-Ali et al. 2016 (JUMP) 2011-2014 Phase 3b
Mead et al. 2015 (ROBUST) 2012-NR Phase II
Mesa et al. 2017 (SIMPLIFY-1) 2013-2016 Phase III (C) Momelotinib Non-inferior spleen response
Harrison et al. 2017 (SIMPLIFY-2) 2014-2016 Phase III (C) Momelotinib Did not meet primary endpoint of spleen volume reduction
Mascarenhas et al. 2018 (PERSIST-2) 2014-2016 Phase III (C) Pacritinib Inferior spleen volume reduction

Patients in COMFORT-II who received "best available therapy" (BAT) generally received no active treatment, Hydroxyurea (Hydrea), or glucocorticoids. Reported efficacy for COMFORT-I is based on the 2017 update. Patients in SIMPLIFY-2 had been previously treated with ruxolitinib but were allowed to receive ruxolitinib as BAT. This was the most commonly used BAT in PERSIST-2.

Targeted therapy

Continued indefinitely

References

  1. INCB 18424-251: Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, Estrov Z, Fridman JS, Bradley EC, Erickson-Viitanen S, Vaddi K, Levy R, Tefferi A. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010 Sep 16;363(12):1117-27. link to original article supplementary appendix contains verified protocol link to PMC article PubMed NCT00509899
  2. COMFORT-I: Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Koumenis IL, Sun W, Sandor V, Kantarjian HM. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):799-807. link to original article supplementary appendix trial protocol contains verified protocol link to PMC article PubMed
    1. Update: Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH, Arcasoy MO, Hexner EO, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Sun W, Sandor V, Kantarjian HM. Efficacy, safety and survival with ruxolitinib treatment in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I. Haematologica. 2013 Dec;98(12):1865-71. Epub 2013 Sep 13. link to original article link to PMC article PubMed
    2. Update: Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH, Arcasoy MO, Hexner EO, Lyons RM, Raza A, Vaddi K, Sun W, Peng W, Sandor V, Kantarjian H. Three-year efficacy, overall survival, and safety of ruxolitinib therapy in patients with myelofibrosis from the COMFORT-I study. Haematologica. 2015 Apr;100(4):479-88. Epub 2015 Jan 23. link to original article link to PMC article PubMed
    3. Pooled update: Vannucchi AM, Kantarjian HM, Kiladjian JJ, Gotlib J, Cervantes F, Mesa RA, Sarlis NJ, Peng W, Sandor V, Gopalakrishna P, Hmissi A, Stalbovskaya V, Gupta V, Harrison C, Verstovsek S; COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015 Sep;100(9):1139-45. Epub 2015 Jun 11. link to original article link to PMC article PubMed
    4. Update: Verstovsek S, Mesa RA, Gotlib J, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner EO, Lyons RM, Paquette R, Raza A, Jones M, Kornacki D, Sun K, Kantarjian H; COMFORT-I investigators. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial. J Hematol Oncol. 2017 Feb 22;10(1):55. link to original article link to PMC article PubMed
  3. COMFORT-II: Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):787-98. link to original article contains verified protocol PubMed content property of HemOnc.org NCT00934544
    1. Update: Cervantes F, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Sirulnik A, Stalbovskaya V, McQuitty M, Hunter DS, Levy RS, Passamonti F, Barbui T, Barosi G, Harrison CN, Knoops L, Gisslinger H. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013 Dec 12;122(25):4047-53. Epub 2013 Oct 30. Erratum in: Blood. 2016 Dec 22;128(25):3013. link to original article PubMed
    2. Pooled update: Vannucchi AM, Kantarjian HM, Kiladjian JJ, Gotlib J, Cervantes F, Mesa RA, Sarlis NJ, Peng W, Sandor V, Gopalakrishna P, Hmissi A, Stalbovskaya V, Gupta V, Harrison C, Verstovsek S; COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015 Sep;100(9):1139-45. Epub 2015 Jun 11. link to original article link to PMC article PubMed
    3. Update: Harrison CN, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Gisslinger H, Knoops L, Cervantes F, Jones MM, Sun K, McQuitty M, Stalbovskaya V, Gopalakrishna P, Barbui T. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016 Aug;30(8):1701-7. Epub 2016 May 23. link to original article link to PMC article PubMed
  4. ROBUST: Mead AJ, Milojkovic D, Knapper S, Garg M, Chacko J, Farquharson M, Yin J, Ali S, Clark RE, Andrews C, Ktiouet Dawson M, Harrison C. Response to ruxolitinib in patients with intermediate-1-, intermediate-2-, and high-risk myelofibrosis: results of the UK ROBUST Trial. Br J Haematol. 2015 Jul;170(1):29-39. Epub 2015 Mar 30. link to original article contains protocol PubMed NCT01558739
  5. JUMP: Al-Ali HK, Griesshammer M, le Coutre P, Waller CF, Liberati AM, Schafhausen P, Tavares R, Giraldo P, Foltz L, Raanani P, Gupta V, Tannir B, Ronco JP, Ghosh J, Martino B, Vannucchi AM. Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial. Haematologica. 2016 Sep;101(9):1065-73. Epub 2016 May 31. link to original article link to PMC article PubMed NCT01493414
  6. SIMPLIFY-1: Mesa RA, Kiladjian JJ, Catalano JV, Devos T, Egyed M, Hellmann A, McLornan D, Shimoda K, Winton EF, Deng W, Dubowy RL, Maltzman JD, Cervantes F, Gotlib J. SIMPLIFY-1: a phase III randomized trial of momelotinib versus ruxolitinib in Janus kinase inhibitor-naïve patients with myelofibrosis. J Clin Oncol. 2017 Dec 1;35(34):3844-3850. Epub 2017 Sep 20. link to original article PubMed NCT01969838
  7. SIMPLIFY-2: Harrison CN, Vannucchi AM, Platzbecker U, Cervantes F, Gupta V, Lavie D, Passamonti F, Winton EF, Dong H, Kawashima J, Maltzman JD, Kiladjian JJ, Verstovsek S. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol. 2018 Feb;5(2):e73-e81. Epub 2017 Dec 20. link to original article PubMed NCT02101268
  8. PERSIST-2: Mascarenhas J, Hoffman R, Talpaz M, Gerds AT, Stein B, Gupta V, Szoke A, Drummond M, Pristupa A, Granston T, Daly R, Al-Fayoumi S, Callahan JA, Singer JW, Gotlib J, Jamieson C, Harrison C, Mesa R, Verstovsek S. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018 May 1;4(5):652-659. Epub 2018 Mar 8. link to original article link to PMC article PubMed NCT02055781

Investigational agents

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