Bomedemstat as an investigative treatment for myeloproliferative neoplasms

References

• Spivak JL, Longo DL. Myeloproliferative Neoplasms. N Engl J Med. 2017;376(22):2168–2181. doi: 10.1056/NEJMra1406186
   PubMed Web of Science ®Google Scholar
• Yassin MA, Taher A, Mathews V, et al. MERGE: a multinational, multicenter observational registry for myeloproliferative neoplasms in Asia, including middle east, Turkey, and Algeria. Cancer Med. 2020;9(13):4512–4526. doi: 10.1002/cam4.3004
   PubMed Web of Science ®Google Scholar
• Visser O, Trama A, Maynadié M, et al. Incidence, survival and prevalence of myeloid malignancies in Europe. Eur J Cancer. 2012;48(17):3257–3266. doi: 10.1016/j.ejca.2012.05.024
   PubMed Web of Science ®Google Scholar
• Noone A, Howlader N, Krapcho ME. SEER Cancer statistics review, 1975–2015. National Cancer Institute 2018.
   Google Scholar
• Palandri F, Breccia M, Tiribelli M, et al. Risk factors for progression to blast phase and outcome in 589 patients with myelofibrosis treated with ruxolitinib: real-world data. Hematol Oncol. 2020;38(3):372–380. doi: 10.1002/hon.2737
   PubMed Web of Science ®Google Scholar
• Iurlo A, Cattaneo D, Gianelli U. Blast transformation in myeloproliferative neoplasms: risk factors, biological findings, and targeted therapeutic options. Int J Mol Sci. 2019;20(8):20. doi: 10.3390/ijms20081839
   Web of Science ®Google Scholar
• Suleiman Y, Dalia S, Liu J, et al. Clinical Prognostic factors and outcomes of essential thrombocythemia when transformed to myelodysplastic syndrome and acute myeloid leukemia. Blood. 2014;124(21):1821–1821. doi: 10.1182/blood.V124.21.1821.1821
   Web of Science ®Google Scholar
• Yogarajah M, Tefferi A. Leukemic transformation in myeloproliferative neoplasms: a literature review on risk, Characteristics, and outcome. Mayo Clin Proc. 2017;92(7):1118–1128. doi: 10.1016/j.mayocp.2017.05.010
   PubMed Web of Science ®Google Scholar
• Abdulkarim K, Girodon F, Johansson P, et al. AML transformation in 56 patients with Ph− MPD in two well defined populations. Eur J Haematol. 2009;82(2):106–111. doi: 10.1111/j.1600-0609.2008.01163.x
   PubMed Web of Science ®Google Scholar
• Cervantes F, Tassies D, Salgado C, et al. Acute transformation in nonleukemic chronic myeloproliferative disorders: actuarial probability and main characteristics in a series of 218 patients. Acta Haematol. 1991;85(3):124–127. doi: 10.1159/000204873
   PubMed Web of Science ®Google Scholar
• Tam CS, Nussenzveig RM, Popat U, et al. The natural history and treatment outcome of blast phase BCR-ABL− myeloproliferative neoplasms. Blood. 2008;112(5):1628–1637. doi: 10.1182/blood-2008-02-138230
   PubMed Web of Science ®Google Scholar
• Tefferi A, Rumi E, Finazzi G, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013;27(9):1874–1881. doi: 10.1038/leu.2013.163
   PubMed Web of Science ®Google Scholar
• Barbui T, Thiele J, Passamonti F, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011;29(23):3179–3184. doi: 10.1200/JCO.2010.34.5298
   PubMed Web of Science ®Google Scholar
• Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937–951. doi: 10.1182/blood-2009-03-209262
   PubMed Web of Science ®Google Scholar
• Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472–1477. doi: 10.1038/leu.2014.3
   PubMed Web of Science ®Google Scholar
• Duangnapasatit B, Rattarittamrong E, Rattanathammethee T, et al. Clinical manifestations and risk factors for complications of Philadelphia chromosome-negative myeloproliferative neoplasms. Asian Pac J Cancer Prev. 2015;16(12):5013–5018. doi: 10.7314/APJCP.2015.16.12.5013
   PubMedGoogle Scholar
• Guglielmelli P, Pacilli A, Rotunno G, et al. Presentation and outcome of patients with 2016 WHO diagnosis of prefibrotic and overt primary myelofibrosis. Blood. 2017;129(24):3227–3236. doi: 10.1182/blood-2017-01-761999
   PubMed Web of Science ®Google Scholar
• Barbui T, Tefferi A, Vannucchi AM, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia. 2018;32(5):1057–1069. doi: 10.1038/s41375-018-0077-1
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Barzilai M, Kirgner I, Ellis M, et al. Characteristics and outcome of Philadelphia(Ph) negative myeloproliferative neoplasms(MPN) in patients younger than 45 years - a multicenter retrospective study. Blood. 2017;130:2917–2917.
   Web of Science ®Google Scholar
• Tefferi A. Primary myelofibrosis: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol. 2014;89(9):915–925. doi: 10.1002/ajh.23703
   PubMed Web of Science ®Google Scholar
• Rotunno G, Mannarelli C, Guglielmelli P, et al. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood. 2014;123(10):1552–1555. doi: 10.1182/blood-2013-11-538983
   PubMed Web of Science ®Google Scholar
• Cuthbert D, Stein BL. Polycythemia vera-associated complications: pathogenesis, clinical manifestations, and effects on outcomes. J blood Med 2019; 10: 359–371. doi : 10.2147/JBM.S189922
   PubMed Web of Science ®Google Scholar
• Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J. 2015;5(11):e366. doi: 10.1038/bcj.2015.95
   PubMed Web of Science ®Google Scholar
• Mesa R, Miller CB, Thyne M, et al. Myeloproliferative neoplasms (MPNs) have a significant impact on patients’ overall health and productivity: the MPN landmark survey. BMC Cancer. 2016;16(1):167. doi: 10.1186/s12885-016-2208-2
   PubMedGoogle Scholar
• Oon SF, Singh D, Tan TH, et al. Primary myelofibrosis: spectrum of imaging features and disease-related complications. Insights Imaging. 2019;10(1):71. doi: 10.1186/s13244-019-0758-y
   PubMed Web of Science ®Google Scholar
• Cervantes F. How I treat splenomegaly in myelofibrosis. Blood Cancer J. 2011;1(10):e37. doi: 10.1038/bcj.2011.36
   PubMed Web of Science ®Google Scholar
• Tefferi A. The forgotten myeloproliferative disorder: myeloid metaplasia. Oncology. 2003;8(3):225–231. doi: 10.1634/theoncologist.8-3-225
   Google Scholar
• Murphy IG, Mitchell EL, Raso-Barnett L, et al. Imaging features of myeloproliferative neoplasms. Clin Radiol. 2017;72(10):801–809. doi: 10.1016/j.crad.2017.05.014
   PubMed Web of Science ®Google Scholar
• Barbui T, Carobbio A, Cervantes F, et al. Thrombosis in primary myelofibrosis: incidence and risk factors. Blood. 2010;115(4):778–782. doi: 10.1182/blood-2009-08-238956
   PubMed Web of Science ®Google Scholar
• Hultcrantz M, Kristinsson SY, Andersson TM, et al. Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study. J Clin Oncol. 2012;30(24):2995–3001. doi: 10.1200/JCO.2012.42.1925
   PubMed Web of Science ®Google Scholar
• Tefferi A, Guglielmelli P, Larson DR, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014;124(16):2507–2513. quiz 2615. doi: 10.1182/blood-2014-05-579136
   PubMed Web of Science ®Google Scholar
• Vannucchi AM, Harrison CN. Emerging treatments for classical myeloproliferative neoplasms. Blood. 2017;129(6):693–703. doi: 10.1182/blood-2016-10-695965
   PubMed Web of Science ®Google Scholar
• Tefferi A. Primary myelofibrosis: 2019 update on diagnosis, risk-stratification and management. Am J Hematol. 2018;93(12):1551–1560. doi: 10.1002/ajh.25230
   PubMed Web of Science ®Google Scholar
• Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management. Am J Hematol. 2019;94(1):133–143. doi: 10.1002/ajh.25303
   PubMed Web of Science ®Google Scholar
• Espasandin YR, Glembotsky AC, Grodzielski M, et al. Anagrelide platelet-lowering effect is due to inhibition of both megakaryocyte maturation and proplatelet formation: insight into potential mechanisms. J Thromb Haemost. 2015;13(4):631–642. doi: 10.1111/jth.12850
   PubMed Web of Science ®Google Scholar
• Mazzucconi MG, Baldacci E, Latagliata R, et al. Anagrelide in essential thrombocythemia (ET): results from 150 patients over 25 years by the “Ph1‐negative Myeloproliferative Neoplasms Latium Group”. Eur J Haematol. 2020;105(3):335–343. doi: 10.1111/ejh.13454
   PubMed Web of Science ®Google Scholar
• Birgegård G, Besses C, Griesshammer M, et al. Treatment of essential thrombocythemia in Europe: a prospective long-term observational study of 3649 high-risk patients in the evaluation of Anagrelide efficacy and long-term safety study. Haematologica. 2018;103(1):51–60. doi: 10.3324/haematol.2017.174672
   PubMed Web of Science ®Google Scholar
• Harrison CN, Campbell PJ, Buck G, et al. Hydroxyurea compared with Anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005;353(1):33–45. doi: 10.1056/NEJMoa043800
   PubMed Web of Science ®Google Scholar
• Ejerblad E, Kvasnicka HM, Thiele J, et al. Diagnosis according to World Health Organization determines the long-term prognosis in patients with myeloproliferative neoplasms treated with anagrelide: results of a prospective long-term follow-up. Hematology. 2013;18(1):8–13. doi: 10.1179/1607845412Y.0000000023
   PubMed Web of Science ®Google Scholar
• England J, Gupta V. Novel therapies vs hematopoietic cell transplantation in myelofibrosis: who, when, how? Hematology Am Soc Hematol Educ Program 2021. 2021;2021(1):453–462. doi: 10.1182/hematology.2021000279
   PubMedGoogle Scholar
• Breccia M, Baratè C, Benevolo G, et al. Tracing the decision-making process for myelofibrosis: diagnosis, stratification, and management of ruxolitinib therapy in real-word practice. Ann Hematol. 2020;99(1):65–72. doi: 10.1007/s00277-019-03847-z
   PubMed Web of Science ®Google Scholar
• National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN guidelines): myeloproliferative neoplasms (version 1.2020). National Comprehensive Cancer Network 2020.
   Google Scholar
• Barbui T, Barosi G, Birgegard G, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29(6):761–770. doi: 10.1200/JCO.2010.31.8436
   PubMed Web of Science ®Google Scholar
• Greenfield G, McPherson S, Mills K, et al. The ruxolitinib effect: understanding how molecular pathogenesis and epigenetic dysregulation impact therapeutic efficacy in myeloproliferative neoplasms. J Transl Med. 2018;16(1). doi: 10.1186/s12967-018-1729-7
   PubMedGoogle Scholar
• Bewersdorf JP, Jaszczur SM, Afifi S, et al. Beyond ruxolitinib: fedratinib and other emergent treatment options for myelofibrosis. Cancer Manage Res 2019; volume 11: 10777–10790. 10.2147/CMAR.S212559.
   PubMed Web of Science ®Google Scholar
• Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799–807. doi: 10.1056/NEJMoa1110557
   PubMed Web of Science ®Google Scholar
• Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787–798. doi: 10.1056/NEJMoa1110556
   PubMed Web of Science ®Google Scholar
• Verstovsek S, Mesa RA, Gotlib J, et al. 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;10(1):55. doi: 10.1186/s13045-017-0417-z
   PubMedGoogle Scholar
• Harrison CN, Vannucchi AM, Kiladjian JJ, et al. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016;30(8):1701–1707. doi: 10.1038/leu.2016.148
   PubMed Web of Science ®Google Scholar
• Verstovsek S, Gotlib J, Mesa RA, et al. Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses. J Hematol Oncol. 2017;10(1):156. doi: 10.1186/s13045-017-0527-7
   PubMed Web of Science ®Google Scholar
• Harrison C, Kiladjian J-J, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787–798. doi: 10.1056/NEJMoa1110556
   PubMed Web of Science ®Google Scholar
• Deininger M, Radich J, Burn TC, et al. The effect of long-term ruxolitinib treatment on JAK2p.V617F allele burden in patients with myelofibrosis. Blood. 2015;126(13):1551–1554. doi: 10.1182/blood-2015-03-635235
   PubMed Web of Science ®Google Scholar
• Mullally A, Hood J, Harrison C, et al. Fedratinib in myelofibrosis. Blood Adv. 2020;4(8):1792–1800. doi: 10.1182/bloodadvances.2019000954
   PubMed Web of Science ®Google Scholar
• Newberry KJ, Patel K, Masarova L, et al. Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation. Blood. 2017;130(9):1125–1131. doi: 10.1182/blood-2017-05-783225
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Pemmaraju N, Kantarjian H, Nastoupil L, et al. Characteristics of patients with myeloproliferative neoplasms with lymphoma, with or without JAK inhibitor therapy. Blood. 2019;133(21):2348–2351. doi: 10.1182/blood-2019-01-897637
   PubMed Web of Science ®Google Scholar
• Saha C, Fedratinib HC. Fedratinib, the first selective JAK2 inhibitor approved for treatment of myelofibrosis – an option beyond ruxolitinib. Expert Review Of Hematology. 2022;15(7):583–595. doi: 10.1080/17474086.2022.2098105
   PubMed Web of Science ®Google Scholar
• Kahl P, Gullotti L, Heukamp LC, et al. Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence. Cancer Res. 2006;66(23):11341–11347. doi: 10.1158/0008-5472.CAN-06-1570
   PubMed Web of Science ®Google Scholar
• Lim S, Janzer A, Becker A, et al. Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis. 2010;31(3):512–520. doi: 10.1093/carcin/bgp324
   PubMed Web of Science ®Google Scholar
• Metzger E, Wissmann M, Yin N, et al. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature. 2005;437(7057):436–439. doi: 10.1038/nature04020
   PubMed Web of Science ®Google Scholar
• Schulte JH, Lim S, Schramm A, et al. Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res. 2009;69(5):2065–2071. doi: 10.1158/0008-5472.CAN-08-1735
   PubMed Web of Science ®Google Scholar
• Goardon N, Marchi E, Atzberger A, et al. Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. Cancer Cell. 2011;19(1):138–152. doi: 10.1016/j.ccr.2010.12.012
   PubMed Web of Science ®Google Scholar
• Harris WJ, Huang X, Lynch JT, et al. The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell. 2012;21(4):473–487. doi: 10.1016/j.ccr.2012.03.014
   PubMed Web of Science ®Google Scholar
• Somervaille TC, Matheny CJ, Spencer GJ, et al. Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells. Cell Stem Cell. 2009;4(2):129–140. doi: 10.1016/j.stem.2008.11.015
   PubMed Web of Science ®Google Scholar
• Somervaille TC, Cleary ML. Identification and characterization of leukemia stem cells in murine MLL-AF9 acute myeloid leukemia. Cancer Cell. 2006;10(4):257–268. doi: 10.1016/j.ccr.2006.08.020
   PubMed Web of Science ®Google Scholar
• Zhang W, Zecca L, Wilson B, et al. Human neuromelanin: an endogenous microglial activator for dopaminergic neuron death. Front Biosci (Elite Ed). 2013;5(1):1–11. doi: 10.2741/E591
   PubMedGoogle Scholar
• Sprüssel A, Schulte J, Weber S, et al. Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation. Leukemia. 2012;26(9):2039–2051. doi: 10.1038/leu.2012.157
   PubMed Web of Science ®Google Scholar
• Jutzi JS, Kleppe M, Dias J, et al. LSD1 inhibition prolongs survival in mouse models of MPN by selectively targeting the disease clone. Hemasphere. 2018;2(3):2. doi: 10.1097/HS9.0000000000000054
   Web of Science ®Google Scholar
• Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLOS Med. 2006;3(7):e270. doi: 10.1371/journal.pmed.0030270
   PubMed Web of Science ®Google Scholar
• Gill H, Palandri F, Ross DM, et al. A phase 2 study of the LSD1 inhibitor bomedemstat (IMG-7289) for the treatment of essential thrombocythemia (ET). Blood. 2022;140(Supplement 1):1784–1787. doi: 10.1182/blood-2022-159047
   Google Scholar
• Pettit KM, Gill H, Yacoub A, et al. A phase 2 study of the LSD1 inhibitor bomedemstat (IMG-7289) for the treatment of advanced myelofibrosis (MF): updated results and genomic analyses. Blood. 2022;140(Supplement 1):9717–9720. doi: 10.1182/blood-2022-167122
   Google Scholar