Myelofibrosis
Section editor | |
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Sanjay R. Mohan, MD, MSCI Vanderbilt University Nashville, TN, USA |
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9 regimens on this page
11 variants on this page
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This page covers the treatment of both primary and secondary myelofibrosis.
Guidelines
ESMO
- 2015: Vannucchi et al. Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
NCCN
- NCCN does not have guidelines at this granular level; please go to the Myeloproliferative neoplasms category page.
All lines of therapy
Danazol monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
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Cervantes et al. 2005 | 1995-11 to 2004-08 | Non-randomized | ||
Verstovsek et al. 2023 (MOMENTUM) | 2020-04-24 to 2021-12-03 | Phase 3 (C) | Momelotinib | Inferior TSS response rate at 24 weeks |
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 contains dosing details in abstract PubMed
- 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 contains dosing details in abstract PubMed NCT04173494
- PACIFICA: NCT03165734
Fedratinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
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Pardanani et al. 2015 (JAKARTA) | 2011-12 to 2012-09 | Phase 3 (E-RT-esc) | Fedratinib; 500 mg/d | Not reported |
Placebo | Superior spleen response (primary endpoint) |
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 contains dosing details in manuscript PubMed NCT01437787
Hydroxyurea monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mesa et al. 2017 (PERSIST-1) | 2013-2014 | Phase 3 (C) | Pacritinib | Inferior spleen volume reduction |
Note: this was the most commonly used "best available therapy" (BAT) in PERSIST-1.
Chemotherapy
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 PubMed NCT01773187
- PACIFICA: NCT03165734
Lenalidomide monotherapy
Regimen
Study | Evidence |
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Tefferi et al. 2006 | Phase 2 |
Targeted therapy
- Lenalidomide (Revlimid) 10 mg PO once per day
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 contains dosing details in abstract PubMed
Pacritinib monotherapy
Regimen
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" | Superior spleen volume reduction (primary endpoint) |
Mascarenhas et al. 2018 (PERSIST-2) | 2014-2016 | Phase 3 (E-RT-switch-ic) | "Best available therapy" | Superior spleen volume reduction (co-primary endpoint) |
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 PubMed 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 PubMed 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 contains dosing details in abstract PubMed NCT02055781
Pomalidomide monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Begna et al. 2010 (PO-MMM-PI-0007) | NR | 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
- 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, 2 mg/day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tefferi et al. 2009 (CC-4047-MMM-001) | 2007-NR | Randomized Phase 2 (E-esc) | 1. Pomalidomide & Prednisone; 2 mg/day 2. Pomalidomide & Prednisone; 0.5 mg/day 3. Prednisone |
Not reported |
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 PubMed 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 contains dosing details in manuscript PubMed
- 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 dosing details in manuscript link to PMC article PubMed 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-NR | Randomized Phase 2, <20 in this arm (E-esc) | 1. Pomalidomide 2. Pomalidomide & Prednisone; 0.5 mg/day 3. Prednisone |
Not reported |
Targeted therapy
- Pomalidomide (Pomalyst) 2 mg PO once per day
Glucocorticoid therapy
- 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, 0.5 mg/day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tefferi et al. 2009 (CC-4047-MMM-001) | 2007-NR | Randomized Phase 2 (E-esc) | 1. Pomalidomide 2. Pomalidomide & Prednisone; 2 mg/day 3. Prednisone |
Not reported |
Targeted therapy
- Pomalidomide (Pomalyst) 0.5 mg PO once per day
Glucocorticoid therapy
- 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
- 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 NCT00463385
Prednisone monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tefferi et al. 2009 (CC-4047-MMM-001) | 2007-NR | Randomized Phase 2 (C) | 1. Pomalidomide 2. Pomalidomide & Prednisone; 2 mg/day 3. Pomalidomide & Prednisone; 0.5 mg/day |
Not reported |
Glucocorticoid therapy
- 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
- 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 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-NR | Phase 2 | ||
Verstovsek et al. 2012 (COMFORT-I) | 2009-09 to 2010-04 | Phase 3 (E-RT-esc) | Placebo | Seems to have superior OS1 (secondary endpoint) Median OS: NYR vs 200 weeks (HR 0.69, 95% CI 0.50-0.96) |
Harrison et al. 2012 (COMFORT-II) | 2009-07-01 to 2010-01-22 | Phase 3 (E-RT-switch-ooc) | "Best available therapy" | Might have superior OS2 (secondary endpoint) Median OS: NYR vs 4.1 y (HR 0.67, 95% CI 0.44-1.02) |
Al-Ali et al. 2016 (JUMP) | 2011-2014 | Phase 3b | ||
Mead et al. 2015 (UK ROBUST) | 2012-NR | Phase 2 | ||
Mesa et al. 2017 (SIMPLIFY-1) | 2013-2016 | Phase 3 (C) | Momelotinib | Non-inferior spleen response |
Harrison et al. 2017 (SIMPLIFY-2) | 2014-2016 | Phase 3 (C) | Momelotinib | Did not meet primary endpoint of spleen volume reduction |
Mascarenhas et al. 2018 (PERSIST-2) | 2014-2016 | Phase 3 (C) | Pacritinib | Inferior spleen volume reduction |
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, Hydroxyurea (Hydrea), or glucocorticoids. 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.
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 contains dosing details in manuscript link to PMC article 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. link to original article supplementary appendix trial protocol contains dosing details in manuscript link to PMC article PubMed 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 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, 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
- 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
- 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
- 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 dosing details in manuscript PubMed content property of 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. link to original article 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. link to original article link to PMC article 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. link to original article link to PMC article PubMed
- 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 contains dosing details in abstract PubMed 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 PubMed 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 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. link to original article PubMed NCT02101268
- 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
- PACIFICA: NCT03165734