Treatment with Tyrosine Kinase Inhibitors in Chronic Myeloproliferative Neoplasms: Pros and Cons
Myeloproliferative neoplasms (MPNs) are a group of hematological disorders characterized by proliferation of one or more than one myeloid lineage. Genetically they express single or multiple mutations of the Janus tyrosine kinase receptors. Advances in understanding molecular and cytogenetic pathophysiology of MPNs led to further identification of different mutations rather than the classical break point cluster region Abelson (BCR-ABL). Although the onset of disease in all MPNs is insidious and may be asymptomatic, also MPNs run a slowly progressive course however they carry the potential of blastic transformation. Furthermore, peripheral blood leucocytosis, thrombocytosis or erythroctosis can lead to a wide array of fatal complications. Originally treatment of MPNs based on cytoreduction and supportive measures. Tyrosine kinase inhibitors (TKIs) are a group of anti-neoplastic drugs that specifically targeting malignant cells. Many studies proved the efficacy and safety of TKIs in management of patients with MPNs. This study was conducted to evaluate TKIs, pros and cons.
Safaa A. A. Khaled,
Treatment with Tyrosine Kinase Inhibitors in Chronic Myeloproliferative Neoplasms: Pros and Cons, American Journal of Internal Medicine.
Vol. 4, No. 4,
2016, pp. 66-74.
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, 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: 937-951.
Campbell LJ. Cytogenetics of myeloproliferative neoplasms. Methods Mol Biol. 2011; 730: 89-98.
James C, Ugo V, Casadevall N, Constantinescu SN, Vainchenker W. A JAK2 mutation in myeloproliferative disorders: pathogenesis and therapeutic and scientific prospects. Trends Mol Med. 2005; 11: 546-554.
James C, Ugo V, Le Couédic JP, Staerk J, Delhommeau F, Lacout C, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005; 434(7037): 1144-1148.
Rollison DE, Howlader N, Smith MT, Strom SS, Merritt WD, Ries LA, et al. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood. 2008; 112: 45-52.
Espey DK, Wu XC, Swan J, Wiggins C, Jim MA, Ward E, et al. Annual report to the nation on the status of cancer, 1975-2004 featuring cancer in American Indians and Alaska Natives. Cancer. 2007; 110: 2119-2152
Lahaye T, Riehm B, Berger U, Paschka P, Müller MC, Kreil S, et al. Response and resistance in 300 patients with BCR-ABL-positive leukemia treated with imatinib in a single center: a 4.5-year follow up. Cancer 2005; 103: 1659–1669.
Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti- Passerini C, et al. International STI571 CML Study Group Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002; 346: 645–652.
Redaelli S, Piazza R, Rostagno R, Magistroni V, Perini P, Marega M, et al. Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol 2009, 27: 469-471.
Vannucchi A, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, et al. Ruxolitinib proves superior to best available therapy in a prospective, randomized, phase 3 study (RESPONSE) in patients with polycythemia vera resistant to or intolerant of hydroxyurea. Haematologica. 2014; 99 (s1): 790; Abstract LB2436
Tefferi A. JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths. Blood 2012; 119 (12): 2721-2730
Dusing R, Weisser B, Mengden T, Vetter H. Changes in antihypertensive therapy-the role of adverse effects and compliance. Blood Press 1998; 7: 313–5.
Osterberg L, Blaschke T: Adherence to medication. N Engl J Med 2005; 353: 487-497.
Darkow T, Henk HJ, Thomas SK, Feng W, Baladi JF, Goldberg GA, et al. Treatment interruptions and non-adherence with imatinib and associated healthcare costs: A retrospective analysis among managed care patients with chronic myelogenous leukaemia. Pharmacoeconomics 25: 481-496, 2007.
Tefferi A, Vardiman JW. The diagnostic interface between histology and molecular tests in myeloproliferative disorders. Curr Opin Hematol 2007; 14: 115–122.
Barosi G, Ambrosetti A, Finelli C, Grossi A, Leoni P, Liberato NL, et al. The Italian consensus conference on diagnostic criteria for myelofibrosis with myeloid metaplasia. Br J Haematol 1999; 104: 730–737.
Tefferi A. Primary myelofibrosis: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol. 2014; 89(9): 915-925.
Haferlach T, Bacher U, Kern W, Schnittger S, Haferlach C. The diagnosis of BCR/ABL-negative chronic myeloproliferative diseases (CMPD): a comprehensive approach based on morphology, cytogenetics, and molecular markers. Ann Hematol. 2008; 87: 1-10.
Kantarjian HM, Cortes J, Guilhot F, Hochhaus A, Baccarani M, Lokey L. Diagnosis and management of chronic myeloid leukemia: a survey of American and European practice patterns. Cancer 2007; 109: 1365–1375.
Goldman JM, Druker BJ. Chronic myeloid leukemia: current treatment options. Blood 2001; 98: 2039-2042.
Geyer HL, Mesa RA. Therapy for myeloproliferative neoplasms: when, which agent, and how? Blood 2014; 124 (24): 3529-3537.
Kiladjian JJ, Chevret S, Dosquet C, Chomienne C, Rain JD. Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980. J Clin Oncol. 2011; 29 (29): 3907-3913.
Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011; 29 (6): 761-770.
Jin J, Sklar GE, Min Sen Oh V, Chuen Li S. Factors affecting therapeutic compliance: A review from the patient's perspective. Ther Clin Risk Manag 2008; 4 (1): 269-86.
National Comprehensive Cancer Network. Clinical practice guidelines in oncology, v. 1. 2007; 1–48. Available at: http://www.nccn.org. visited on 24-3-2016.
WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. 64th WMA General Assembly, Fortaleza, Brazil, October 2013. http://www.wma.net/en/30publications/10policies/b3/. Visited on Jan. 2016.
Tefferi A, Thiele J, Vannucchi AM, Barbui T. An overview on CALR and CSF3R mutations and a proposal for revision of WHO diagnostic criteria for myeloproliferative neoplasms. Leukemia. 2014; 28 (7): 1407-1413.
Nangalia J, Massie CE, Baxter EJ, Gundem G, Wedge DC, Avezov E, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013; 369 (25): 2391-2405.
Verstovsek S, Kantarjian SH, Mesa RA, Pardanani, Cortes-Franco J, Thomas DA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010; 363 (12): 1117-1127.
Khaled SA, Abdel-Aziz NM. Demographic, clinical, and hematologic characteristics of patients with chronic myeloid leukemia in Upper Egypt: association with treatment responses. Egyptian J Haematol 2015; 40: 195–200.
Chen Y, Wang H, Kantarjian H, Cortes J. Trends in chronic myeloid leukemia incidence and survival in the United States from 1975 to 2009. Leuk Lymphoma 2013; 54: 1411.
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014; 64: 9.
Cherington C, Slack JL, Leis J, Biezen AJ, Bornhäuser M, Di Bartolomeo P, et al. Allogeneic stem cell transplantation for myeloproliferative neoplasm in blast phase. Leuk Res. 2012; 36 (9): 1147-1151.
Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010, 362: 2260-2270.
Noens L, van Lierde MA, De Bock R, Verhoef G, Zachée P, Berneman Z, et al: Prevalence, determinants, and outcomes of non adherence to imatinib therapy in patients with chronic myeloid leukemia: The ADAGIO study. Blood 113: 5401-5411, 2009.
Partridge AH, Avorn J, Wang PS, Winer EP. Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst 94: 652-661, 2002.
Marin D, Bazeos A, Mahon FX, Eliasson L, Milojkovic D, Bua M, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010. 10; 28 (14): 2381-8.
Ruddy K, Mayer E, Partridge A: Patient adherence and persistence with oral anticancer treatment. CA Cancer J Clin 59: 56-66, 2009.
Masiello D, Gorospe G, Yang AS: The occurrence and management of fluid retention associated with TKI therapy in CML, with a focus on dasatinib. J Hematol Oncol 2009, 2: 46.
Edesa WA, Abdel- Malek RR. Impact of imatinib interruption and duration of prior hydroxyurea on the treatment outcome in patients with chronic myeloid leukemia: Single institution experience. Journal of the Egyptian National Cancer Institute (2015) 27, 69–75.
Alsobhi E, Abrar MB, Abdelaal M, Alsaeed A, Absi A, Zahrani Z, et al. Response to Imatinib therapy in adult patients with chronic myeloid leukemia in Saudi population: single center study. Leuk Lymphoma 2014; 23: 1–15.
Gugliotta G, Castagnetti F, Palandri F, Breccia M, Intermesoli T, Capucci A, et al. Gruppo Italiano Malattie Ematologiche dell’Adulto CML Working Party. Frontline imatinib treatment of chronic myeloid leukemia: no impact of age on outcome, a survey by the GIMEMA CML Working Party. Blood 2011; 117 (21): 5591–9.
Deininger M, O’Brien SG, Guilhot F, Goldman JM, Hochhaus A, Hughes TP, et al. International randomized study of interferon vs STI571 (IRIS) 8-year follow up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with imatinib. Blood 2009, 114 (Suppl): 462, (abstract 1126).
Cramer JA, Scheyer RD, Mattson RH. Compliance declines between clinic visits. Arch Intern Med 150: 1509-1510, 1990.