Myelofibrosis

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This page covers the treatment of both primary and secondary myelofibrosis.
Last updated on 2024-12-02:10 regimens on this page
12 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.
==BSH==
*2024: McLornan et al. Diagnosis and evaluation of prognosis of myelofibrosis: a British Society for Haematology guideline 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.
=JAK inhibitor-naive=
==Danazol monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Cervantes et al. 2005 	1995-11 to 2004-08 	Non-randomized	 	
Awaiting publication (PACIFICA)	2017-ongoing 	Phase 3 (C) 	Pacritinib	TBD if different co-primary endpoints of spleen volume/TSS response rate at 24 weeks
====Endocrine therapy====
*Danazol (Danocrine) 300 mg PO twice per day
Continued indefinitely
===References===
#Cervantes F, Alvarez-Larrán A, Domingo A, Arellano-Rodrigo E, Montserrat E. Efficacy and tolerability of danazol as a treatment for the anaemia of myelofibrosis with myeloid metaplasia: long-term results in 30 patients. Br J Haematol. 2005 Jun;129(6):771-5. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#PACIFICA: NCT03165734
==Fedratinib monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Pardanani et al. 2015 (JAKARTA)	2011-12 to 2012-09 	Phase 3 (E-RT-esc)	1. Fedratinib; 500 mg/d	Not reported
Pardanani et al. 2015 (JAKARTA)	2011-12 to 2012-09 	Phase 3 (E-RT-esc)	2. Placebo 	Higher spleen response at week 24 (primary endpoint)36% vs 1%
====Targeted therapy====
*Fedratinib (Inrebic) 400 mg PO once per day on days 1 to 28
28-day cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT01437787
==Hydroxyurea monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Mesa et al. 2017 (PERSIST-1) 	2013-01-08 to 2014-08-01	Phase 3 (C)	Pacritinib	Lower SVR35% at week 24 (primary endpoint)SVR35% at week 24: 5% vs 19%
Awaiting publication (PACIFICA)	2017-ongoing 	Phase 3 (C)	Pacritinib	TBD if different co-primary endpoints of spleen volume/TSS response rate at 24 weeks
Note: this was the most commonly used "best available therapy" (BAT) in PERSIST-1.
====Chemotherapy====
*Hydroxyurea (Hydrea)
===References===
# 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 link to PMC article does not contain dosing details EuroPMC NCT01773187
#PACIFICA: NCT03165734
==Imetelstat monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Tefferi et al. 2015 (CR107110)	Not reported 	Phase 2
====Targeted therapy====
*Imetelstat (Rytelo) 9.4 mg/kg IV over 2 hours once on day 1
21-day cycle for 9 or more cycles
===References===
# CR107110: Tefferi A, Lasho TL, Begna KH, Patnaik MM, Zblewski DL, Finke CM, Laborde RR, Wassie E, Schimek L, Hanson CA, Gangat N, Wang X, Pardanani A. A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis. N Engl J Med. 2015 Sep 3;373(10):908-19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01731951
==Lenalidomide monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Tefferi et al. 2006a	2004-03-05 to 2005-06-15	Phase 2
Tefferi et al. 2006b	2004-07-21 to 2005-07-08	Phase 2
Note: this manuscript reports on two independently conducted phase 2 studies, with some differences in the duration of therapy.
====Targeted therapy====
*Lenalidomide (Revlimid) 10 mg PO once per day on days 1 to 28
28-day cycle for at least 3 up to 24 cycles
===References===
# 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 dosing details in abstract have been reviewed by our editors EuroPMC
==Momelotinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Mesa et al. 2017 (SIMPLIFY-1)	2013-2016 	Phase 3 (E-switch-ic)	Ruxolitinib	Non-inferior SVR35% at 24 weeks (primary endpoint)SVR35% at 24 weeks: 26.5% vs 29%
====Targeted therapy====
*Momelotinib (Ojjaara) 200 mg PO once per day
Continued indefinitely
===References===
# 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 link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01969838
==Pacritinib monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Komrokji et al. 2015 (SB1518-2008-003)	2010 	Phase 2 	 	
Mesa et al. 2017 (PERSIST-1) 	2013-01-08 to 2014-08-01	Phase 3 (E-switch-ic) 	"Best available therapy"	Higher SVR35% at week 24 (primary endpoint)SVR35% at week 24: 19% vs 5%
Mascarenhas et al. 2018 (PERSIST-2) 	2014-2016 	Phase 3 (E-RT-switch-ic)	"Best available therapy"	Higher SVR35% at week 24 (co-primary endpoint)SVR35% at week 24: 18% vs 3%
====Targeted therapy====
*Pacritinib (Vonjo) 200 mg PO twice per day
Continued indefinitely
===References===
# SB1518-2008-003: Komrokji RS, Seymour JF, Roberts AW, Wadleigh M, To LB, Scherber R, Turba E, Dorr A, Zhu J, Wang L, Granston T, Campbell MS, Mesa RA. Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. Blood. 2015 Apr 23;125(17):2649-55. Epub 2015 Mar 11. link to original article link to PMC article EuroPMC NCT00745550
# 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 link to PMC article EuroPMC NCT01773187
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02055781
#PACIFICA: NCT03165734
==Pomalidomide monotherapy==
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Begna et al. 2010 (PO-MMM-PI-0007)	Not reported 	Phase 2 	 	
Tefferi et al. 2016 (RESUME) 	2010-2012 	Phase 3 (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 on days 1 to 28
28-day cycles
====Dose and schedule modifications====
*In PO-MMM-PI-0007, escalation up to 2 mg PO once per day allowed after first six cycles
===Regimen variant #2, 2 mg/day===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Tefferi et al. 2009 (CC-4047-MMM-001)	2007 to not reported	Randomized Phase 2 (E-esc)	1. Pomalidomide & Prednisone; 2 mg/day2. Pomalidomide & Prednisone; 0.5 mg/day 3. Prednisone	Not reported
====Targeted therapy====
*Pomalidomide (Pomalyst) 2 mg PO once per day on days 1 to 28
28-day cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00463385
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01178281
==Pomalidomide & Prednisone==
===Regimen variant #1, 2 mg/day===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Tefferi et al. 2009 (CC-4047-MMM-001)	2007 to not reported	Randomized Phase 2, <20 in this arm (E-esc)	1. Pomalidomide2. Pomalidomide & Prednisone; 0.5 mg/day3. Prednisone	Not reported
====Targeted therapy====
*Pomalidomide (Pomalyst) 2 mg PO once per day on days 1 to 28
====Glucocorticoid therapy====
*Prednisone (Sterapred) as follows:
**Cycle 1: 30 mg PO once per day on days 1 to 28
**Cycle 2: 15 mg PO once per day on days 1 to 28
**Cycle 3: 15 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27
28-day cycles
===Regimen variant #2, 0.5 mg/day===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Tefferi et al. 2009 (CC-4047-MMM-001)	2007 to not reported	Randomized Phase 2 (E-esc)	1. Pomalidomide2. Pomalidomide & Prednisone; 2 mg/day 3. Prednisone	Not reported
====Targeted therapy====
*Pomalidomide (Pomalyst) 0.5 mg PO once per day on days 1 to 28
====Glucocorticoid therapy====
*Prednisone (Sterapred) as follows:
**Cycle 1: 30 mg PO once per day on days 1 to 28
**Cycle 2: 15 mg PO once per day on days 1 to 28
**Cycle 3: 15 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27
28-day cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00463385
==Prednisone monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Tefferi et al. 2009 (CC-4047-MMM-001)	2007 to not reported	Randomized Phase 2 (C)	1. Pomalidomide2. Pomalidomide & Prednisone; 2 mg/day3. Pomalidomide & Prednisone; 0.5 mg/day	Not reported
Awaiting publication (PACIFICA) 	2017-ongoing 	Phase 3 (C) 	Pacritinib 	TBD if different co-primary endpoints of spleen volume/TSS response rate at 24 weeks
====Glucocorticoid therapy====
*Prednisone (Sterapred) as follows:
**Cycle 1: 30 mg PO once per day on days 1 to 28
**Cycle 2: 15 mg PO once per day on days 1 to 28
**Cycle 3: 15 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27
28-day cycle for 3 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00463385
#PACIFICA: NCT03165734
==Ruxolitinib monotherapy==
===Regimen===
COMFORT: COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Treatment
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Verstovsek et al. 2010 (INCB 18424-251)	2007 to not reported 	Phase 2 	 	
Verstovsek et al. 2012 (COMFORT-I) 	2009-09 to 2010-04 	Phase 3 (E-RT-esc) 	Placebo 	Seems to have longer OS1 (secondary endpoint)Median OS: NYR vs 200 weeks(HR 0.69, 95% CI 0.50-0.96)Higher SVR35% at week 24 (primary endpoint)
Harrison et al. 2012 (COMFORT-II) 	2009-07-01 to 2010-01-22	Phase 3 (E-RT-switch-ooc)	"Best available therapy"	Might have longer OS2 (secondary endpoint)Median OS: NYR vs 4.1 y(HR 0.67, 95% CI 0.44-1.02)Higher SVR35% at week 48 (primary endpoint)
Al-Ali et al. 2016 (JUMP) 	2011-2014 	Phase 3b 	 	
Mead et al. 2015 (UK ROBUST) 	2012 to not reported 	Phase 2 	 	
Mesa et al. 2017 (SIMPLIFY-1) 	2013-2016 	Phase 3 (C) 	Momelotinib 	Non-inferior SVR35% at 24 weeks (primary endpoint)SVR35% at 24 weeks: 29% vs 26.5%
Mascarenhas et al. 2018 (PERSIST-2) 	2014-2016 	Phase 3 (C) 	Pacritinib 	Lower SVR35% at week 24 (co-primary endpoint)SVR35% at week 24: 3% vs 18%
Awaiting publication (PACIFICA) 	2017-ongoing 	Phase 3 (C) 	Pacritinib 	TBD if different co-primary endpoints of spleen volume/TSS response rate at 24 weeks
1Reported efficacy for COMFORT-I is based on the 2017 update.
2Reported efficacy for COMFORT-II is based on the 2016 update.
Note: Patients in COMFORT-II who received "best available therapy" (BAT) generally received no active treatment (33%), Hydroxyurea (Hydrea) (47%), or glucocorticoids (16%). This was the most commonly used BAT in PERSIST-2.
====Targeted therapy====
*Ruxolitinib (Jakafi) 10 to 25 mg PO twice per day
Continued indefinitely
===References===
# 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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. link to original article supplementary appendix trial protocol dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00952289
## 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 EuroPMC
## 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 EuroPMC
## 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 EuroPMC
## 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC content property of HemOnc.org NCT00934544
##HRQoL analysis: Harrison CN, Mesa RA, Kiladjian JJ, Al-Ali HK, Gisslinger H, Knoops L, Squier M, Sirulnik A, Mendelson E, Zhou X, Copley-Merriman C, Hunter DS, Levy RS, Cervantes F, Passamonti F, Barbui T, Barosi G, Vannucchi AM. Health-related quality of life and symptoms in patients with myelofibrosis treated with ruxolitinib versus best available therapy. Br J Haematol. 2013 Jul;162(2):229-39. Epub 2013 May 14. link to original article EuroPMC
## 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 EuroPMC
## 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 EuroPMC
## 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 EuroPMC
# UK 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 dosing details in abstract have been reviewed by our editors EuroPMC NCT01558739
# 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 EuroPMC NCT01493414
# 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 link to PMC article EuroPMC NCT01969838
# 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 does not contain dosing details in manuscript EuroPMC NCT02055781
#PACIFICA: NCT03165734
=JAK inhibitor-exposed=
==Danazol monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Verstovsek et al. 2023 (MOMENTUM)	2020-04-24 to 2021-12-03	Phase 3 (C)	Momelotinib	Lower TSS response rate at 24 weeks
====Endocrine therapy====
*Danazol (Danocrine) 300 mg PO twice per day
Continued indefinitely
===References===
#MOMENTUM: Verstovsek S, Gerds AT, Vannucchi AM, Al-Ali HK, Lavie D, Kuykendall AT, Grosicki S, Iurlo A, Goh YT, Lazaroiu MC, Egyed M, Fox ML, McLornan D, Perkins A, Yoon SS, Gupta V, Kiladjian JJ, Granacher N, Lee SE, Ocroteala L, Passamonti F, Harrison CN, Klencke BJ, Ro S, Donahue R, Kawashima J, Mesa R; MOMENTUM Study Investigators. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023 Jan 28;401(10373):269-280. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT04173494
##Update: Gerds AT, Verstovsek S, Vannucchi AM, Al-Ali HK, Lavie D, Kuykendall AT, Grosicki S, Iurlo A, Goh YT, Lazaroiu MC, Egyed M, Fox ML, McLornan D, Perkins A, Yoon SS, Gupta V, Kiladjian JJ, Granacher N, Lee SE, Ocroteala L, Passamonti F, Harrison CN, Oh S, Klencke BJ, Yu J, Donahue R, Kawashima J, Mesa R. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis previously treated with a JAK inhibitor (MOMENTUM): an updated analysis of an international, double-blind, randomised phase 3 study. Lancet Haematol. 2023 Sep;10(9):e735-e746. Epub 2023 Jul 27. link to original article EuroPMC
##HRQoL analysis: Mesa RA, Harrison C, Palmer JM, Gupta V, McLornan DP, McMullin MF, Kiladjian JJ, Foltz L, Platzbecker U, Fox ML, Mead AJ, Ross DM, Oh ST, Perkins AC, Leahy MF, Kawashima J, Ro S, Donahue R, Gorsh B, Deheshi S, Verstovsek S. Patient-reported Outcomes and Quality of Life in Anemic and Symptomatic Patients With Myelofibrosis: Results From the MOMENTUM Study. Hemasphere. 2023 Oct 24;7(11):e966. link to original article link to PMC article EuroPMC
==Fedratinib monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Harrison et al. 2024 (FREEDOM2)	2019-09-09 to 2022-06-24	Phase 3 (E-switch-ooc)	Best available therapy	Higher SVR35% at end of cycle 6 (primary endpoint)
====Prior treatment criteria====
*Ruxolitinib, with progression or intolerance
====Targeted therapy====
*Fedratinib (Inrebic) 400 mg PO once per day on days 1 to 28
28-day cycles
===References===
# FREEDOM2: Harrison CN, Mesa R, Talpaz M, Al-Ali HK, Xicoy B, Passamonti F, Palandri F, Benevolo G, Vannucchi AM, Mediavilla C, Iurlo A, Kim I, Rose S, Brown P, Hernandez C, Wang J, Kiladjian JJ. Efficacy and safety of fedratinib in patients with myelofibrosis previously treated with ruxolitinib (FREEDOM2): results from a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Haematol. 2024 Oct;11(10):e729-e740. Epub 2024 Sep 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03952039
==Imetelstat monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Tefferi et al. 2015 (CR107110)	Not reported 	Phase 2
====Targeted therapy====
*Imetelstat (Rytelo) 9.4 mg/kg IV over 2 hours once on day 1
21-day cycle for 9 or more cycles
===References===
# CR107110: Tefferi A, Lasho TL, Begna KH, Patnaik MM, Zblewski DL, Finke CM, Laborde RR, Wassie E, Schimek L, Hanson CA, Gangat N, Wang X, Pardanani A. A Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis. N Engl J Med. 2015 Sep 3;373(10):908-19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01731951
==Momelotinib monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Harrison et al. 2017 (SIMPLIFY-2)	2014-2016 	Phase 3 (E-switch-ooc)	"Best available therapy"	Did not meet primary endpoint of spleen volume reduction
Verstovsek et al. 2023 (MOMENTUM)	2020-04-24 to 2021-12-03	Phase 3 (E-switch-ooc)	Danazol 	Higher TSS response rate at 24 weeks (primary endpoint)
====Targeted therapy====
*Momelotinib (Ojjaara) 200 mg PO once per day
Continued indefinitely
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02101268
#MOMENTUM: Verstovsek S, Gerds AT, Vannucchi AM, Al-Ali HK, Lavie D, Kuykendall AT, Grosicki S, Iurlo A, Goh YT, Lazaroiu MC, Egyed M, Fox ML, McLornan D, Perkins A, Yoon SS, Gupta V, Kiladjian JJ, Granacher N, Lee SE, Ocroteala L, Passamonti F, Harrison CN, Klencke BJ, Ro S, Donahue R, Kawashima J, Mesa R; MOMENTUM Study Investigators. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023 Jan 28;401(10373):269-280. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04173494
##Update: Gerds AT, Verstovsek S, Vannucchi AM, Al-Ali HK, Lavie D, Kuykendall AT, Grosicki S, Iurlo A, Goh YT, Lazaroiu MC, Egyed M, Fox ML, McLornan D, Perkins A, Yoon SS, Gupta V, Kiladjian JJ, Granacher N, Lee SE, Ocroteala L, Passamonti F, Harrison CN, Oh S, Klencke BJ, Yu J, Donahue R, Kawashima J, Mesa R. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis previously treated with a JAK inhibitor (MOMENTUM): an updated analysis of an international, double-blind, randomised phase 3 study. Lancet Haematol. 2023 Sep;10(9):e735-e746. Epub 2023 Jul 27. link to original article EuroPMC
##HRQoL analysis: Mesa RA, Harrison C, Palmer JM, Gupta V, McLornan DP, McMullin MF, Kiladjian JJ, Foltz L, Platzbecker U, Fox ML, Mead AJ, Ross DM, Oh ST, Perkins AC, Leahy MF, Kawashima J, Ro S, Donahue R, Gorsh B, Deheshi S, Verstovsek S. Patient-reported Outcomes and Quality of Life in Anemic and Symptomatic Patients With Myelofibrosis: Results From the MOMENTUM Study. Hemasphere. 2023 Oct 24;7(11):e966. link to original article link to PMC article EuroPMC
==Pacritinib monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Mascarenhas et al. 2018 (PERSIST-2)	2014-2016 	Phase 3 (E-RT-switch-ic)	"Best available therapy"	Higher SVR35% at week 24 (co-primary endpoint)SVR35% at week 24: 18% vs 3%
====Targeted therapy====
*Pacritinib (Vonjo) 200 mg PO twice per day
Continued indefinitely
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02055781
Category:Myelofibrosis regimens
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Category:Myeloproliferative neoplasms