Top advances of the year: Myeloproliferative neoplasms.
ET
MF
MPN
PV
essential thrombocythemia
myelofibrosis
myeloproliferative neoplasm
polycythemia vera
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
01 12 2023
01 12 2023
Historique:
medline:
6
11
2023
pubmed:
28
9
2023
entrez:
28
9
2023
Statut:
ppublish
Résumé
The rapid pace of drug development in hematology has led to multiple approvals for myelofibrosis (MF) and polycythemia vera (PV) in recent years. Moreover, there are many innovative agents and combinations being explored for myeloproliferative neoplasms (MPNs). In the past year, there have been several advances in MF, PV, and essential thrombocythemia. In MF, investigational approaches are focusing on strategies to optimize inhibition of signal transduction (including JAK inhibition), modify epigenetics, enhance apoptosis, target DNA replication, transform host immunity, and/or alter the tumor microenvironment. In PV, ropeginterferon alfa-2b has been introduced to the market in the United States, and data continue to accumulate to support the safety and efficacy of this treatment. Hepcidin mimesis is also emerging as a novel way to treat erythrocytosis. In essential thrombocythemia, ropeginterferon alfa-2b is being evaluated, as are therapies to modify epigenetics and inhibit CALR. The enhanced focus on MPNs brings hope that our field can improve morbidity and mortality in this group of diseases.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3685-3691Informations de copyright
© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.
Références
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
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
Vannucchi AM, Kantarjian HM, Kiladjian JJ, et al. 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;100(9):1139-1145. doi:10.3324/haematol.2014.119545
Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015;372(5):426-435. doi:10.1056/nejmoa1409002
Pardanani A, Harrison C, Cortes JE, et al. Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: a randomized clinical trial. JAMA Oncol. 2015;1(5):643-651. doi:10.1001/jamaoncol.2015.1590
Harrison CN, Schaap N, Vannucchi AM, et al. Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single-arm, open-label, non-randomised, phase 2, multicentre study. Lancet Haematol. 2017;4(7):e317-e324. doi:10.1016/s2352-3026(17)30088-1
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, 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(22):5825-5835. doi:10.1182/bloodadvances.2020003314
Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: a phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor-naive 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
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
Accessed September 21, 2023. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Ojjaara/pdf/OJJAARA-PI-PIL.PDF
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
Masarova L, Alhuraiji A, Bose P, et al. Significance of thrombocytopenia in patients with primary and postessential thrombocythemia/polycythemia vera myelofibrosis. Eur J Haematol. 2018;100(3):257-263. doi:10.1111/ejh.13005
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
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
Al-Ali HK, Stalbovskaya V, Gopalakrishna P, Perez-Ronco J, Foltz L. Impact of ruxolitinib treatment on the hemoglobin dynamics and the negative prognosis of anemia in patients with myelofibrosis. Leuk Lymphoma. 2016;57(10):2464-2467. doi:10.3109/10428194.2016.1146950
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
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
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. doi:10.1182/bloodadvances.2023010151
Oh S, Mesa R, Harrison C, et al. MPN-145 retrospective analysis of anemia benefit of pacritinib from the PERSIST-2 Trial. Clin Lymphoma Myeloma Leuk. 2022;22(Suppl 2):S327. doi:10.1016/s2152-2650(22)01439-2
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
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
Passamonti F, Foran JM, Tandra A, et al. The combination of navitoclax and ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis mediates responses suggestive of disease modification. Blood. 2022;140(Suppl 1):583-585. doi:10.1182/blood-2022-157949
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
Kuykendall AT, Sun L, Mascarenhas J, et al. Favorable overall survival with imetelstat in relapsed/refractory myelofibrosis patients compared with real-world data. Ann Hematol. 2022;101(1):139-146. doi:10.1007/s00277-021-04683-w
Al-Ali H, Delgado R, Lange A. KRT-232, a first-in-class, murine double minute 2 inhibitor (MDM2), for myelofibrosis (MF) relapsed or refractory (R/R) to Janus-associated kinase inhibitor (JAKI) treatment (tx). HemaSphere. 2020;4:S1.
Vachani P, Lange A, Delgado RG, et al. Potential disease-modifying activity of navtemadlin (KRT-232), a first-in-class MDM2 inhibitor, correlates with clinical benefits in relapsed/refractory myelofibrosis (MF). Blood. 2021;138(Suppl 1):3581. doi:10.1182/blood-2021-147543
Niebel D, Kirfel J, Janzen V, Holler T, Majores M, Gutgemann I. Lysine-specific demethylase 1 (LSD1) in hematopoietic and lymphoid neoplasms. Blood. 2014;124(1):151-152. doi:10.1182/blood-2014-04-569525
Sprussel A, Schulte JH, 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
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
Gill H, Au L, Tsai D, et al. S211: efficacy and safety of ropeginterferon alfa-2b for pre-fibrotic primary myelofibrosis and DIPSS low/intermediate-1 risk myelofibrosis: updated results and genomic characteristics. HemaSphere. 2023;7(S3):e9247372. doi:10.1097/01.hs9.0000967756.92473.72
Gisslinger H, Zagrijtschuk O, Buxhofer-Ausch V, et al. Ropeginterferon alfa-2b, a novel IFNalpha-2b, induces high response rates with low toxicity in patients with polycythemia vera. Blood. 2015;126(15):1762-1769. doi:10.1182/blood-2015-04-637280
Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020;7(3):e196-e208. doi:10.1016/s2352-3026(19)30236-4
Kiladjian JJ, Klade C, Georgiev P, et al. Long-term outcomes of polycythemia vera patients treated with ropeginterferon Alfa-2b. Leukemia. 2022;36(5):1408-1411. doi:10.1038/s41375-022-01528-x
Barbui T, Vannucchi AM, De Stefano V, et al. Ropeginterferon alfa-2b versus phlebotomy in low-risk patients with polycythaemia vera (Low-PV study): a multicentre, randomised phase 2 trial. Lancet Haematol. 2021;8(3):e175-e184. doi:10.1016/s2352-3026(20)30373-2
Hoffman R, Ginzburg Y, Kremyanskaya M, et al. Rusfertide (PTG-300) treatment in phlebotomy-dependent polycythemia vera patients. J Clin Oncol. 2022;40(16_suppl):7003. doi:10.1200/jco.2022.40.16_suppl.7003
Pemmaraju N, Kuykendall A, Kremyanskaya M, et al. MPN-469 rusfertide (PTG-300) treatment interruption reverses hematological gains and upon reinitiation, restoration of clinical benefit observed in patients with polycythemia Vera. Clin Lymphoma Myeloma Leuk. 2022;22(Suppl 2):S338-S339. doi:10.1016/s2152-2650(22)01462-8
Verstovsek S, Kuykendall A, Hoffman R, et al. Verify: a phase 3 study of the hepcidin mimetic rusfertide (PTG-300) in patients with polycythemia vera. Blood. 2022;140(Suppl 1):3929-3931. doi:10.1182/blood-2022-163755
Zanardi TA, Korbmacher B, Boone L, et al. Safety, pharmacokinetic, and pharmacodynamic evaluation of a 2'-(2-methoxyethyl)-D-ribose antisense oligonucleotide-triantenarry N-Acetyl-galactosamine conjugate that targets the human transmembrane protease serine 6. J Pharmacol Exp Therapeut. 2021;377(1):51-63. doi:10.1124/jpet.120.000222
IONIS. A study to evaluate IOIS-TMPRSS6-LRx (ISIS 702843) in patients with polycythemia vera. Accessed March 27, 2023. https://ionistrials.com/a-study-to-evaluate-ionis-tmprss6-lrx-isis-702843-in-patients-with-polycythemia-vera/
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
Passamonti F, Rumi E, Pungolino E, et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med. 2004;117(10):755-761. doi:10.1016/j.amjmed.2004.06.032
Okikiolu J, Woodley C, Cadman-Davies L, et al. Real world experience with ropeginterferon alpha-2b (Besremi) in essential thrombocythaemia and polycythaemia vera following exposure to pegylated interferon alfa-2a (Pegasys). Leuk Res Rep. 2023;19:100360. doi:10.1016/j.lrr.2022.100360
Berkowitz C, Chen S-L, Reeves B. Ropegiterferon alfa-2b-Njft for treatment myeloproliferative neoplasms: a single institution experience. Blood. 2022;140(Suppl 1):12254-12255. doi:10.1182/blood-2022-164733
Chen C-C, Kuo M-C, Su Y-J, et al. Treatment of ropeginterferon alpha-2b achieves hematologic remission and molecular response in patients with hydroxyurea- and/or anagrelide-resistant/intolerant myeloproliferative neoplasms. Blood. 2021;138(Suppl 1):4631. doi:10.1182/blood-2021-147746
Verstovsek S, Mesa R, Mascarenhas J, et al. MPN-546 A single-arm multicenter study to assess the efficacy, safety, and tolerability of ropeginterferon alfa-2b-njft (P1101) in North American adults with essential thrombocythemia. Clin Lymphoma, Myeloma & Leukemia. 2022;22(Suppl 2):S342-S343. doi:10.1016/s2152-2650(22)01469-0
Verstovsek S, Komatsu N, Gill H, et al. SURPASS-ET: phase III study of ropeginterferon alfa-2b versus anagrelide as second-line therapy in essential thrombocythemia. Future Oncol. 2022;18(27):2999-3009. doi:10.2217/fon-2022-0596
Mesa R, Komatsu N, Gill H, et al. MPN-545 surpass-ET: ropeginterferon alfa-2b (P1101) vs. anagrelide as second line therapy in essential thrombocythemia. Clin Lymphoma, Myeloma & Leukemia. 2022;22(Suppl 2):S342. doi:10.1016/s2152-2650(22)01468-9
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(Suppl 1):1784-1787. doi:10.1182/blood-2022-159047
Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379-2390. doi:10.1056/nejmoa1311347
Reis E, Buonpane R, Celik H, et al. Discovery of INCA033989, a monoclonal antibody that selectively antagonizes mutant calreticulin oncogenic function in myeloproliferative neoplasms (MPNs). Blood. 2022;140(Suppl 1):14-15. doi:10.1182/blood-2022-159435