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Review

Treatment of anemia in myelofibrosis: focusing on novel therapeutic options

ORCID Icon, , & ORCID Icon
Pages 27-37 | Received 08 Jul 2023, Accepted 09 Dec 2023, Published online: 19 Dec 2023

References

  • Tefferi A. Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023;98(5):801–821. Epub ahead of print. PMID: 36680511. doi: 10.1002/ajh.26857
  • Passamonti F, Harrison CN, Mesa RA, et al. Anemia in myelofibrosis: Current and emerging treatment options. Crit Rev Oncol Hematol. 2022;180:103862. doi: 10.1016/j.critrevonc.2022.103862
  • Barbui T, Thiele J, Gisslinger H, et al. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J. 2018;8(2):15. doi: 10.1038/s41408-018-0054-y
  • Barosi G, Mesa RA, Thiele J, et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the international working group for myelofibrosis research and treatment. Leukemia. 2008;22(2):437–438. doi: 10.1038/sj.leu.2404914
  • Tefferi A, Lasho TL, Finke CM, et al. Targeted deep sequencing in primary myelofibrosis. Blood Adv. 2016;1(2):105–111. doi: 10.1182/bloodadvances.2016000208
  • Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the international working group for myelofibrosis research and treatment. Blood. 2009;113(13):2895–2901. doi: 10.1182/blood-2008-07-170449
  • Tefferi A, Lasho TL, Jimma T, et al. One thousand patients with primary myelofibrosis: the mayo clinic experience. Mayo Clin Proc. 2012;87(1):25–33. doi: 10.1016/j.mayocp.2011.11.001
  • Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (international working group for myeloproliferative neoplasms research and treatment). Blood. 2010;115(9):1703–1708. doi: 10.1182/blood-2009-09-245837
  • Scherber R, Dueck AC, Johansson P, et al. The myeloproliferative neoplasm symptom assessment form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood. 2011;118(2):401–408. doi: 10.1182/blood-2011-01-328955
  • Tefferi A, Hudgens S, Mesa R, et al. Use of the functional assessment of Cancer therapy–anemia in persons with myeloproliferative neoplasm-associated myelofibrosis and anemia. Clin Ther. 2014;36(4):560–6. doi: 10.1016/j.clinthera.2014.02.016
  • National Comprehensive Cancer Network. NCCN Guidelines Version 3. 2022 Myelofibrosis. Accessed Apr, 2023.
  • Elli EM, Iurlo A, Aroldi A, et al. Deferasirox in the management of iron-overload in patients with myelofibrosis: a multicentre study from the rete ematologica lombarda (IRON-M study). Br J Haematol. 2019;186(5):e123–e126. doi: 10.1111/bjh.15964
  • Hernández-Boluda JC, Correa JG, García-Delgado R, et al. Predictive factors for anemia response to erythropoiesis-stimulating agents in myelofibrosis. Eur J Haematol. 2017;98(4):407–414. doi: 10.1111/ejh.12846
  • Crisà E, Cilloni D, Elli EM, et al. The use of erythropoiesis-stimulating agents is safe and effective in the management of anaemia in myelofibrosis patients treated with ruxolitinib. Br J Haematol. 2018;182(5):701–704. doi: 10.1111/bjh.15450
  • Hernández-Boluda JC, Martínez-Trillos A, García-Gutiérrez V, et al. Long-term results of prednisone treatment for the anemia of myelofibrosis. Leuk Lymphoma. 2016;57(1):120–124. doi: 10.3109/10428194.2015.1046866
  • Cervantes F, Isola IM, Alvarez-Larrán A, et al. Danazol therapy for the anemia of myelofibrosis: assessment of efficacy with current criteria of response and long-term results. Ann Hematol. 2015;94(11):1791–1796. doi: 10.1007/s00277-015-2435-7
  • Gowin K, Kosiorek H, Dueck A, et al. Multicenter phase 2 study of combination therapy with ruxolitinib and danazol in patients with myelofibrosis. Leuk Res. 2017;60:31–35. doi: 10.1016/j.leukres.2017.06.005
  • Luo X, Xu Z, Li B, et al. Thalidomide plus prednisone with or without danazol therapy in myelofibrosis: a retrospective analysis of incidence and durability of anemia response. Blood Cancer J. 2018;8(1):9. doi: 10.1038/s41408-017-0029-4
  • Thapaliya P, Tefferi A, Pardanani A, et al. International working group for myelofibrosis research and treatment response assessment and long-term follow-up of 50 myelofibrosis patients treated with thalidomide-prednisone based regimens. Am J Hematol. 2011;86(1):96–98. doi: 10.1002/ajh.21892
  • Mesa RA, Yao X, Cripe LD, et al. Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology group (ECOG) phase 2 trial E4903. Blood. 2010;116(22):4436–4438. doi: 10.1182/blood-2010-05-287417
  • Castillo-Tokumori F, Talati C, Al AN, et al. Retrospective Analysis of the Clinical Use and Benefit of Lenalidomide and Thalidomide in Myelofibrosis. Clin Lymphoma Myeloma Leuk. 2020;20(12):e956–e960. doi: 10.1016/j.clml.2020.07.006
  • Tefferi A, Al-Ali HK, Barosi G, et al. A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence. Leukemia. 2017;31(4):896–902. doi: 10.1038/leu.2016.300
  • Masarova L, Verstovsek S, Kantarjian H, et al. Immunotherapy based approaches in myelofibrosis. Expert Rev Hematol. 2017;10(10):903–914. doi: 10.1080/17474086.2017.1366853
  • Begna KH, Pardanani A, Mesa R, et al. Long-term outcome of pomalidomide therapy in myelofibrosis. Am J Hematol. 2012;87(1):66–68. doi: 10.1002/ajh.22233
  • Chowdhury O, O’Sullivan J, Barkas N, et al. Spliceosome mutations are common in persons with myeloproliferative neoplasm-associated myelofibrosis with RBC-transfusion-dependence and correlate with response to pomalidomide. Leukemia. 2021;35(4):1197–1202. doi: 10.1038/s41375-020-0979-6
  • Mesa RA, Tefferi A. Palliative splenectomy in myelofibrosis with myeloid metaplasia. Leuk Lymphoma. 2001;42(5):901–911. doi: 10.3109/10428190109097709
  • Malato A, Rossi E, Tiribelli M, et al. Splenectomy in myelofibrosis: indications, efficacy, and complications. Clin Lymphoma Myeloma Leuk. 2020;20(9):588–595. doi: 10.1016/j.clml.2020.04.015
  • Gupta V, Harrison C, Hexner EO, et al. The impact of anemia on overall survival in patients with myelofibrosis treated with ruxolitinib in the COMFORT studies. Haematologica. 2016;101(12):e482–e484. doi: 10.3324/haematol.2016.151449
  • Palandri F, Breccia M, Bonifacio M, et al. Life after ruxolitinib: reasons for discontinuation, impact of disease phase, and outcomes in 218 patients with myelofibrosis. Cancer. 2020;126(6):1243–1252. doi: 10.1002/cncr.32664
  • Cervantes F, Ross DM, Radinoff A, et al. Efficacy and safety of a novel dosing strategy for ruxolitinib in the treatment of patients with myelofibrosis and anemia: the REALISE phase 2 study. Leukemia. 2021;35(12):3455–3465. doi: 10.1038/s41375-021-01261-x
  • Pardanani A, Tefferi A, Masszi T, et al. Updated results of the placebo-controlled, phase III JAKARTA trial of fedratinib in patients with intermediate-2 or high-risk myelofibrosis. Br J Haematol. 2021;195(2):244–248. doi: 10.1111/bjh.17727
  • Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: a Phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor-naïve patients with myelofibrosis. J Clin Oncol. 2017;35(34):3844–3850. doi: 10.1200/JCO.2017.73.4418
  • Harrison CN, Vannucchi AM, Platzbecker U, et al. 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;5(2):e73–e81. doi: 10.1016/S2352-3026(17)30237-5
  • Oh ST, Talpaz M, Gerds AT, et al. ACVR1/JAK1/JAK2 inhibitor momelotinib reverses transfusion dependency and suppresses hepcidin in myelofibrosis phase 2 trial. Blood Adv. 2020;4(18):4282–4291. doi: 10.1182/bloodadvances.2020002662
  • Verstovsek S, Gerds AT, Vannucchi AM, et al. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023;401(10373):269–280. doi: 10.1016/S0140-6736(22)02036-0
  • Zhang Y, Zhou H, Jiang Z, et al. Safety and efficacy of jaktinib in the treatment of Janus kinase inhibitor-naïve patients with myelofibrosis: results of a phase II trial. Am J Hematol. 2022;97(12):1510–1519. doi: 10.1002/ajh.26709
  • Mesa RA, Vannucchi AM, Mead A, et al. 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;4(5):e225–e236. doi: 10.1016/S2352-3026(17)30027-3
  • Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018;4(5):652–659. doi: 10.1001/jamaoncol.2017.5818
  • Gerds AT, Vannucchi AM, Passamonti F, et al. A Phase 2 study of luspatercept in patients with myelofibrosis-associated anemia. Blood. 2019;134(Supplement 1):557–557. [Abstract]. doi: 10.1182/blood-2019-122546
  • Gerds AT, Vannucchi AM, Passamonti F, et al. Duration of response to luspatercept in patients (pts) requiring red blood cell (RBC) transfusions with myelofibrosis (MF) – updated data from the phase 2 ACE-536-MF-001 study. Blood. 2020;136(Supplement 1):47–48. [Abstract]. doi: 10.1182/blood-2020-137265
  • Talpaz M, Rampal RK, Verstovsek S, et al. CPI-0610, a bromodomain and extraterminal domain protein (BET) inhibitor, as monotherapy in advanced myelofibrosis patients refractory/intolerant to JAK inhibitor: update from phase 2 MANIFEST study. Blood. 2020;134. Paper 2163 [Abstract]. https://ash.confex.com/ash/2020/webprogram/Paper139842.html
  • Verstovsek S, Mascarenhas J, Kremyanskaya M, et al. Mechanistic basis and efficacy of targeting the β-catenin-TCF7L2-JMJD6-c-myc axis to overcome resistance to BET inhibitors. Blood. 2020;135(Supplement 1):1255–1269. [Abstract]. doi: 10.1182/blood.2019002922
  • Mascarenhas J, Kremyanskaya M, Patriarca A, et al. MANIFEST: pelabresib in combination with ruxolitinib for janus kinase inhibitor treatment-naïve myelofibrosis. J Clin Oncol. 2023;41:4993–5004. [Abstract] doi: 10.1200/JCO.22.01972
  • Verstovsek S, Hasserjian RP, Pozdnyakova O, et al. PRM-151 in myelofibrosis: efficacy and safety in an open label extension study. Blood. 2018;132(Supplement 1):686. [Abstract]. doi: 10.1182/blood-2018-99-115362
  • Verstovsek S, Talpaz M, Wadleigh M, et al. S828 A RANDOMIZED, DOUBLE BLIND PHASE 2 STUDY OF 3 DIFFERENT DOSES OF PRM-151 IN PATIENTS WITH MYELOFIBROSIS WHO WERE PREVIOUSLY TREATED WITH OR INELIGIBLE FOR RUXOLITINIB. Hemasphere. 2019;3(S1):367. [Abstract]. doi: 10.1097/01.HS9.0000561592.51072.9b
  • Harrison CN, Garcia JS, Somervaille TCP, et al. Addition of navitoclax to ongoing ruxolitinib therapy for patients with myelofibrosis with progression or suboptimal response: phase II safety and efficacy. J Clin Oncol. 2022;40(15):1671–1680. doi: 10.1200/JCO.21.02188
  • Tefferi A, Lasho TL, Begna KH, et al. A Pilot study of the telomerase inhibitor imetelstat for myelofibrosis. N Engl J Med. 2015;373(10):908–919. doi: 10.1056/NEJMoa1310523
  • Mascarenhas J, Komrokji RS, Palandri F, et al. Randomized, Single-Blind, multicenter phase II study of two doses of imetelstat in relapsed or refractory myelofibrosis. J Clin Oncol. 2021;39(26):2881–2892. doi: 10.1200/JCO.20.02864
  • Gerds AT, Savona MR, Scott BL, et al. Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis. Blood Adv. 2020;4:5825–5835. doi: 10.1182/bloodadvances.2020003314
  • Mesa RA, Barosi G, Harrison C, et al. Efficacy and safety of luspatercept versus placebo in patients with myeloproliferative neoplasm-associated myelofibrosis on JAK2 inhibitor therapy and requiring RBC transfusions (INDEPENDENCE trial). Hemasphere. 2021;5:PB1702. [Abstract].
  • https://clinicaltrials.gov/show/NCT05037760
  • Harrison CN, Gupta VK, Gerds AT, et al. Phase III MANIFEST-2: pelabresib + ruxolitinib vs placebo + ruxolitinib in JAK inhibitor treatment-naive myelofibrosis. FutureOncol. 2022;18:2987–2997. doi: 10.2217/fon-2022-0484
  • Mascarenhas J, Saab R, Brackman D, et al. Two phase 1b studies evaluating the safety and tolerability of BET inhibitors, ABBV-744 and Mivebresib, as monotherapies and in combination with ruxolitinib or navitoclax in patients with myelofibrosis. Blood. 2020;136(Supplement 1):18–19. [Abstract]. doi: 10.1182/blood-2020-137686
  • Potluri J, Harb J, Masud AA, et al. A Phase 3, Double-blind, placebo-controlled, randomized study evaluating navitoclax in combination with ruxolitinib in patients with myelofibrosis (TRANSFORM-1). Blood. 2020;136(Supplement 1):4. [Abstract]. doi: 10.1182/blood-2020-139758
  • Dilley K, Harb J, Jalaluddin M, et al. A phase 3, open-label, randomized study evaluating the efficacy and safety of navitoclax plus ruxolitinib versus best available therapy in patients with relapsed/refractory myelofibrosis (TRANSFORM-2). Blood. 2020;136(Supplement 1):8. [Abstract]. doi: 10.1182/blood-2020-139247
  • https://clinicaltrials.gov/show/NCT05371964
  • Mascarenhas J, Harrison CN, Kiladjian JJ, et al. Imetelstat in intermediate-2 or high-risk myelofibrosis refractory to JAK inhibitor: IMpactMF phase III study design. FutureOncol. 2022;18(22):2393–2402. doi: 10.2217/fon-2022-0235
  • Asshoff M, Petzer V, Warr MR, et al. Momelotinib inhibits ACVR1/ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents. Blood. 2017;129(13):1823–1830. doi: 10.1182/blood-2016-09-740092
  • Mesa R, Harrison C, Oh ST, et al. Overall survival in the SIMPLIFY-1 and SIMPLIFY-2 phase 3 trials of momelotinib in patients with myelofibrosis. Leukemia. 2022;36(9):2261–2268. doi: 10.1038/s41375-022-01637-7
  • Tefferi A, Barraco D, Lasho TL, et al. Momelotinib therapy for myelofibrosis: a 7-year follow-up. Blood Cancer J. 2018;8(3):29. doi: 10.1038/s41408-018-0067-6
  • Oh ST, Mesa RA, Harrison CN, et al. Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis. Blood Adv. 2023;7:5835–5842. doi: 10.1182/bloodadvances.2023010151
  • Kubasch AS, Fenaux P, Platzbecker U. Development of luspatercept to treat ineffective erythropoiesis. Blood Adv. 2021;5(5):1565–1575. doi: 10.1182/bloodadvances.2020002177
  • Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382(2):140–151. doi: 10.1056/NEJMoa1908892
  • Cappellini MD, Taher AT. The use of luspatercept for thalassemia in adults. Blood Adv. 2021;5(1):326–333. doi: 10.1182/bloodadvances.2020002725
  • Gangat N, Tefferi A. Myelofibrosis biology and contemporary management. Br J Haematol. 2020;191(2):152–170. doi: 10.1111/bjh.16576
  • Feigenson M, Nathan R, Babbs K, et al. KER-050, a modified ActRIIA ligand trap, alleviates cytopenia arising from multiple etiologies. Blood. 2020;136(Supplement 1):38. [Abstract]. doi: 10.1182/blood-2020-140167
  • Feigenson M, Nathan R, Materna C, et al. Ker-050, a novel inhibitor of Tgfβ Superfamily signaling, induces red Blood cell production by promoting multiple stages of erythroid differentiation. Blood. 2020;136(Supplement 1):34. [Abstract] doi: 10.1182/blood-2020-140364
  • Kleppe M, Koche R, Zou L, et al. Dual targeting of oncogenic activation and inflammatory signaling increases therapeutic efficacy in myeloproliferative neoplasms. Cancer Cell. 2018;33(1):29–43.e7. doi: 10.1016/j.ccell.2017.11.009
  • Zhang L, Cai T, Lin X, et al. Selective inhibition of the second bromodomain of BET family proteins results in robust antitumor activity in preclinical models of acute myeloid Leukemia. Mol Cancer Ther. 2021;20(10):1809–1819. doi: 10.1158/1535-7163.MCT-21-0029
  • de Freitas RM, da Costa Maranduba CM, de Freitas RM, et al. Myeloproliferative neoplasms and the JAK/STAT signaling pathway: an overview. Rev Bras Hematol Hemoter. 2015;37(5):348–53. doi: 10.1016/j.bjhh.2014.10.001

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