Dasatinib in First- and Second-Line Therapy of Chronic Myeloid Leukemia: Efficacy, Safety and Quality of Life

Background & Aims. The article presents results of two observational, prospective, multicenter studies “Quality of Life, Symptom Profile, and Adherence to Treatment in Adult Patients with Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Receiving Dasatinib” (2012–2015) and “Quality of Life and Symptom Profile in Imatinib-Resistant or Intolerant Patients with Chronic Myeloid Leukemia” (2011–2014).

Methods. Data of 107 patients with chronic myeloid leukemia in chronic phase were involved in the real-world analysis — 32 newly diagnosed patients on first-line treatment with dasatinib or after yearly switch to dasatinib after imatinib treatment failure and 75 imatinib-resistant or intolerant patients on second-line treatment with dasatinib. Treatment effectiveness and safety of dasatinib were assessed during first and second-line dasatinib treatment using clinical outcomes as well as quality of life and symptom profile assessment.

Results. The real-world data obtained during observational study in limited population of CML patients conform the results of clinical trials devoted to evaluation of treatment efficacy and safety of dasatinib treatment in first and second-line treatment and demonstrate the importance of patient-reported outcomes. Patient’s quality of life improved within 12 months of the first-line dasatinib therapy according to the following scales: role physical functioning, pain, vitality, social functioning and role emotional functioning. The most pronounced and clinically significant improvement was observed for the role emotional functioning (51.1 vs. 68.9). During the second-line dasatinib treatment, stabilization of quality of life parameters was registered for the following scales: vitality, social functioning, mental health, and pain. Significant improvement of the Integral Quality of Life Index was observed (p < 0.05). Positive dynamics of relevant symptoms was registered. The symptom severity decreased during both the first and second-line therapy.

Conclusion. Quality of life and symptom assessment in CML patients contribute to a better disease control in accordance with the principles of risk-adaptive therapy.

• Tat’yana Ivanovna Ionova Saint Petersburg Multifield Medical Center under the Ministry of Health of Russia, 154 Nabereznaya Reki Fontanki, Saint Petersburg, Russian Federation, 198103; Multinational Center for Quality of Life Research, 1 Artilleriiskaya str., office 152, Saint Petersburg, Russian Federation, 191014 ; Санкт-Петербургский многопрофильный центр Минздрава России, Набережная р. Фонтанки, д. 154, Санкт-Петербург, Российская Федерация, 198103; Межнациональный центр исследования качества жизни, Артиллерийская ул., д. 1, Санкт-Петербург, Российская Федерация, 191014
• N.B. Bulieva I Kant Baltic Federal University, 14 A Nevskogo str., Kaliningrad, Russian Federation, 236041 ; Медицинский институт БФУ им. И. Канта, ул. А. Невского, д. 14, Калининград, Российская Федерация, 236041
• O.Yu. Vinogradova SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-zd, Moscow, Russian Federation, 125284; Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology under the Ministry of Health of the Russian Federation, 1 Samory Mashela str., Moscow, Russian Federation, 117198; NI Pirogov Russian National Research Medical University under the Ministry of Health of the Russian Federation, 1 Ostrovityanova str., Moscow, Russian Federation, 117997 ; Московский городской гематологический центр ГКБ им. С.П. Боткина, 2-й Боткинский пр-д, д. 5, Москва, Российская Федерация, 125284; ФГБУ «Национальный научно-практический центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России, ул. Саморы Машела, д. 1, Москва, Российская Федерация, 117198; ФГБОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России, ул. Островитянова, д. 1, Москва, Российская Федерация, 117997
• T.A. Gritsenko Samara State Medical University under the Ministry of Health of the Russian Federation, 89 Chapaevskaya str., Samara, Russian Federation, 443099 ; ГБОУ ВПО «Самарский государственный медицинский университет» Минздрава России, ул. Чапаевская, д. 89, Самара, Российская Федерация, 443099
• L.K. Kozlova Orenburg State Medical University, 6 Sovetskaya str., Orenburg, Russian Federation, 460000 ; Оренбургский государственный медицинский университет, ул. Советская, д. 6, Оренбург, Российская Федерация, 460000
• G.B. Kuchma Orenburg State Medical University, 6 Sovetskaya str., Orenburg, Russian Federation, 460000 ; Оренбургский государственный медицинский университет, ул. Советская, д. 6, Оренбург, Российская Федерация, 460000
• E.G. Lomaia Federal Almazov North-West Medical Research Centre, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
• E.R. Machyulaitene Outpatient Department, Academician IP Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022 ; Поликлиника с клинико-диагностическим центром, ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова», ул. Л. Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022
• T.P. Nikitina Saint Petersburg Multifield Medical Center under the Ministry of Health of Russia, 154 Nabereznaya Reki Fontanki, Saint Petersburg, Russian Federation, 198103; Multinational Center for Quality of Life Research, 1 Artilleriiskaya str., office 152, Saint Petersburg, Russian Federation, 191014 ; Санкт-Петербургский многопрофильный центр Минздрава России, Набережная р. Фонтанки, д. 154, Санкт-Петербург, Российская Федерация, 198103; Межнациональный центр исследования качества жизни, Артиллерийская ул., д. 1, Санкт-Петербург, Российская Федерация, 191014
• N.V. Novitskaya SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-zd, Moscow, Russian Federation, 125284 ; Московский городской гематологический центр ГКБ им. С.П. Боткина, 2-й Боткинский пр-д, д. 5, Москва, Российская Федерация, 125284
• A.Yu. Rodionova Multinational Center for Quality of Life Research, 1 Artilleriiskaya str., office 152, Saint Petersburg, Russian Federation, 191014 ; Межнациональный центр исследования качества жизни, Артиллерийская ул., д. 1, Санкт-Петербург, Российская Федерация, 191014
• E.I. Usacheva RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022 ; НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова», ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022
• T.V. Shneider Leningrad District Clinical Hospital, 43/49 Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291 ; Ленинградская областная клиническая больница, пр-т Луначарского, д. 43/49, Санкт-Петербург, Российская Федерация, 194291

1. Ломаиа Е.Г., Романова Е.Г., Сбитякова Е.И., Зарицкий А.Ю. Эффективность и безопасность ингибиторов тирозинкиназ 2-го поколения (дазатиниб, нилотиниб) в терапии хронической фазы хронического миелолейкоза. Онкогематология. 2013;8(2):22–33.
2. [Lomaia EG, Romanova EG, Sbityakova EI, Zaritskii AYu. Efficacy and safety of tyrosine kinase inhibitors 2nd generation (dasatinib, nilotinib) in the treatment of chronic phase chronic myeloid leukemia. Onkogematologia. 2013;8(2):22–33. (In Russ)]
3. Efficace F, Cocks K, Breccia M, et al. Time for a new era in the evaluation of targeted therapies for patients with chronic myeloid leukemia: inclusion of quality of life and other patient-reported outcomes. Crit Rev Oncol Hematol. 2012;81(2):123–35. doi: 10.1016/j.critrevonc.2011.02.007. DOI: https://doi.org/10.1016/j.critrevonc.2011.02.007
4. Mauro MJ, Davis C, Zyzynski T, et al. The role of observational studies in optimizing the clinical management of chronic myeloid leukemia. Ther Adv Hematol. 2015;6(1):3–14. doi: 10.1177/2040620714560305. DOI: https://doi.org/10.1177/2040620714560305
5. Абдулкадыров К.М., Абдуллаев А.О., Авдеева Л.Б. и др. Федеральные клинические рекомендации по диагностике и терапии хронического миелолейкоза. Вестник гематологии. 2013;9(3):4–40.
6. [Abdulkadyrov KM, Abdullayev AO, Avdeeva LB, et al. Federal clinical guidelines for diagnosis and treatment of chronic myeloid leukemia. Vestnik gematologii. 2013;9(3):4–40. (In Russ)]
7. Baccarani M, Pileri S, Steegmann J-L, et al. Chronic myeloid leukemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(7): vii72–7. doi: 10.1093/annonc/mds228. DOI: https://doi.org/10.1093/annonc/mds228
8. Туркина А.Г., Хельман Р., Поспелова Т.И. Практические аспекты терапии хронического миелолейкоза в хронической фазе. Онкогематология. 2012;3:8–16.
9. Turkina AG, Hel’man R, Pospelova TI. Practical aspects of treatment of chronic phase chronic myeloid leukemia. Onkogematologiya. 2012;3:8–16. (In Russ)]
10. Голенков А.К., Высоцкая Л.Л., Трифонова Е.В. и др. Эффективность лечения больных хроническим миелолейкозом иматинибом в широкой клинической практике. Онкогематология. 2012;3:17–21.
11. [Golenkov AK, Vysotskaya LL, Trifonova EV, et al. Treatment efficacy of chronic myeloid leukemia with imatinib in clinical practice. Onkogematologiya. 2012;3:17–21. (In Russ)]
12. Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872–84. doi: 10.1182/blood-2013-05-501569. DOI: https://doi.org/10.1182/blood-2013-05-501569
13. Baccarani M, Castagnetti F, Gugliotta G, Rosti G. A review of the European LeukemiaNet recommendations for the management of CML. Ann Hematol. 2015;94(Suppl 2):141–7. doi: 10.1007/s00277-015-2322-2. DOI: https://doi.org/10.1007/s00277-015-2322-2
14. Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia. N Engl J Med. 2010;362(24):2260–70. doi: 10.1056/NEJMoa1002315. DOI: https://doi.org/10.1056/NEJMoa1002315
15. Wei G, Rafiyath S, Liu D. First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib. J Hematol Oncol. 2010;3(1):47. doi: 10.1186/1756-8722-3-47. DOI: https://doi.org/10.1186/1756-8722-3-47
16. Hughes TP, Saglio G, Quintas-Cardama A, et al. BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase. Leukemia. 2015;29(9):1832–8. doi: 10.1038/leu.2015.168. DOI: https://doi.org/10.1038/leu.2015.168
17. Shah N, Kim D, Kantarjian H, et al. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib. Haematologica. 2010;95(2):232–40. doi: 10.3324/haematol.2009.011452. DOI: https://doi.org/10.3324/haematol.2009.011452
18. Rosti G, Castagnetti F, Gugliotta G, et al. Dasatinib and nilotinib in imatinib resistant Philadelphia-positive chronic myelogenous leukemia: a ‘head-to-head’comparison. Leuk Lymphoma. 2010;51(4):583–91. doi: 10.3109/10428191003637282. DOI: https://doi.org/10.3109/10428191003637282
19. Krauth M, Herndlhofer S, Schmook M, et al. Extensive pleural and pericardial effusion in chronic myeloid leukemia during treatment with dasatinib at 100 mg or 50 mg daily. Haematologica. 2011;96(1):163–6. doi: 10.3324/haematol.2010.030494. DOI: https://doi.org/10.3324/haematol.2010.030494
20. Jabbour E, Deininger M, Hochhaus A. Management of adverse events associated with tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Leukemia. 2011;25(2):201–10. doi: 10.1038/leu.2010.215. DOI: https://doi.org/10.1038/leu.2010.215
21. Eskazan AE, Soysal T, Ongoren S, et al. Pleural and pericardial effusions in chronic myeloid leukemia patients receiving low-dose dasatinib therapy. Haematologica. 2011;96(3):e15. doi: 10.3324/haematol.2011.040048. DOI: https://doi.org/10.3324/haematol.2011.040048
22. Nagata Y, Ohashi K, Fukuda S, et al. Clinical features of dasatinib-induced large granular lymphocytosis and pleural effusion. Int J Hematol. 2010;91(5):799–807. doi: 10.1007/s12185-010-0565-1. DOI: https://doi.org/10.1007/s12185-010-0565-1
23. Kim DW, Cleeland CS, Saussele S, et al. Dasatinib in Patients with Chronic Phase Chronic Myeloid Leukemia (CML-CP) with Persistent, Low-Grade Nonhematologic Toxicity to Imatinib: Results from Dasperse (CA180-400). Blood. 2015;126(23):1575. DOI: https://doi.org/10.1182/blood.V126.23.1575.1575
24. Guidelines. Patient-reported outcomes in hematology. The EHA SWG “Quality of Life and Symptoms”. Genoa: Forum Service Editore; 2012. [Internet] Available from: https://www.ehaweb.org/assets/documents/Guidelines-PRO-SWG-QoL.pdf. (accessed 13.03.2017).
25. US Food and Drug Administration. Guidance for industry: patient-reported outcome measures; use in medical product development to support labeling claims. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071975.pdf. (accessed 8.09.2009).
26. Новик А.А., Ионова Т.И. Руководство по исследованию качества жизни в медицине. М.: РАЕН, 2012. 528 с.
27. [Novik AA, Ionova TI. Rukovodstvo po issledovaniyu kachestva zhizni v meditsine (Manual on quality of life assessment in medicine.) Moscow: RAEN Publ.; 2012. 528 p. (In Russ)]
28. Efficacе F, Cardoni A, Cottone F, et al. Tyrosinekinase inhibitors and patient-reported outcomes in chronic myeloid leukemia: A systematic review. Leuk Res. 2013;37(2):206–13. doi: 10.1016/j.leukres.2012.10.021. DOI: https://doi.org/10.1016/j.leukres.2012.10.021
29. Baccarani M, Efficace F, Rosti G. Moving towards patient-centered decision-making in chronic myeloid leukemia: assessment of quality of life and symptom burden. Haematologica. 2014;99(2):205–8. doi: 10.3324/haematol.2013.094045. DOI: https://doi.org/10.3324/haematol.2013.094045
30. Efficace F, Rosti G, Aaronson N, et al. Patient- versus physician-reporting of symptoms and health status in chronic myeloid leukemia. Haematologica. 2014;99(4):788–93. doi: 10.3324/haematol.2013.093724. DOI: https://doi.org/10.3324/haematol.2013.093724
31. Efficace F, Baccarani M, Breccia M. Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population. Blood. 2011;118(17):4554–60. doi: 10.1182/blood-2011-04-347575. DOI: https://doi.org/10.1182/blood-2011-04-347575
32. Kropf P, Barnes G, Tang B, et al. Burden of Tyrosine Kinase Inhibitor Failure in Patients with Chronic Myeloid Leukemia. J Leuk. 2014;3(1):170. doi: 10.4172/2329-6917.1000170. DOI: https://doi.org/10.4172/2329-6917.1000170
33. Snyder CF, Aaronson NK, Choucair AK, et al. Implementing patient-reported outcomes assessment in clinical practice: a review of the options and considerations. Qual Life Res. 2012;21(8):1305–14. doi: 10.1007/s11136-011-0054-x. DOI: https://doi.org/10.1007/s11136-011-0054-x
34. Saussele S, Richter J, Hochhaus A, et al. The concept of treatment-free remission in chronic myeloid leukemia. Leukemia. 2016;30(8):1638–47. doi: 10.1038/leu.2016.115. DOI: https://doi.org/10.1038/leu.2016.115
35. Latagliata R, Breccia M, Carmosino I, et al. ‘Real-life’ results of front-line treatment with imatinib in older patients (≥ 65 years) with newly diagnosed chronic myelogenous leukemia. Leuk Res. 2010;34(11):1472–5. doi: 10.1016/j.leukres.2010.07.001. DOI: https://doi.org/10.1016/j.leukres.2010.07.001
36. Baccarani M, Hoffmann VS, Rosti G, et al. Baseline Characteristics of CML Patients Across Europe – Comparing Real-World Patients with Patient Collectives Included in Clinical Trials. Blood. 2014;124(21):3160. DOI: https://doi.org/10.1182/blood.V124.21.3160.3160
37. Rawlins M. De testimonio: on the evidence for decisions about the use of therapeutic interventions. The Lancet. 2008;372(9656);2152–61. doi: 10.1016/s0140-6736(08)61930-3. DOI: https://doi.org/10.1016/S0140-6736(08)61930-3
38. Silverman S. From randomized controlled trails to observational studies. Am J Med. 2009;122(2);114–20. doi: 10.1016/j.amjmed.2008.09.030. DOI: https://doi.org/10.1016/j.amjmed.2008.09.030
39. Cortes J, Hehlmann R, Gambacorti-Passerini C, et al. Baseline characteristics of patients with chronic myeloid leukemia in a prospective observational study (SIMPLICITY). Blood. 2013;122:4026. DOI: https://doi.org/10.1182/blood.V122.21.4026.4026
40. Nicolini FE, Vantard N, Giraudier S, et al. Prospective Analysis of the Quality of Life of Chronic Phase CML Patients on Second Generation Tyrosine Kinase Inhibitors after Imatinib Failure. An Observational Study. Blood. 2014;124(21):1321. DOI: https://doi.org/10.1182/blood.V124.21.1321.1321
41. Cortes J, Mauro M, Goldberg S, et al. Quality of life during early tyrosine kinase inhibitor treatment as self-reported by chronic myeloid leukemia patients participating in a prospective observational study (SIMPLICITY). Blood. 2011;118:4435. DOI: https://doi.org/10.1182/blood.V118.21.4435.4435
42. Goldberg S, Cortes J, Gambacorti-Passerini C, et al. Cytogenetic and molecular testing in patients with chronic myeloid leukemia (CML) in a prospective observational study (SIMPLICITY). J Clin Oncol. 2014;32:5s, abstr. 7050. DOI: https://doi.org/10.1200/jco.2014.32.15_suppl.7050
43. Goldberg S, Cortes J, Gambacorti-Passerini C, et al. Predictors of performing response monitoring in patients with chronic-phase chronic myeloid leukemia (CP-CML) in a prospective observational study (SIMPLICITY). J Clin Oncol. 2014;32(30):116. doi: 10.1200/jco.2014.32.30_suppl.116. DOI: https://doi.org/10.1200/jco.2014.32.30_suppl.116
44. Савельева М.И., Самарина И.Н., Самойлова О.С. и др. Качество жизни пациентов с хроническим миелолейкозом. Кремлевская медицина. Клинический вестник. 2012;1:60–4.
45. [Savel’eva MI, Samarina IN, Samoilova OS, et al. Quality of life of patients with chronic myeloid leukemia. Kremlevskaya meditsina. Klinicheskii vestnik. 2012;1:60–4. (In Russ)]
46. Давыдкин И.Л., Сиротко И.И., Егорова Г.А. и др. Опыт применения ингибиторов тирозинкиназы у больных хроническим миелолейкозом в Самарской области. Эффективная фармакотерапия. 2013;46:14–9.
47. [Davydkin IL, Sirotko II, Egorova GA, et al. An experience in the use of thyrosine kinase inhibitors in patients with chronic myeloid leukemia in Samara Oblast. Effectivnaya farmakoterapia. 2013;46:14–9. (In Russ)]
48. Carlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83. doi: 10.1016/0021-9681(87)90171-8. DOI: https://doi.org/10.1016/0021-9681(87)90171-8
49. Breccia M, Latagliata R, Stagno F, et al. Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib. Haematologica. 2011;96(10):1457–61. doi: 10.3324/haematol.2011.041251. DOI: https://doi.org/10.3324/haematol.2011.041251
50. Breccia M, Alimena M. Firstline treatment for chronic phase chronic myeloid leukemia patients should be based on a holistic approach. Expert Rev Hematol. 2015;8(1):5–7. doi: 10.1586/17474086.2015.987230. DOI: https://doi.org/10.1586/17474086.2015.987230
51. Saussele S, Krauss MP, Lauseker M, et al. Comorbidity, measured by the Charlson index, has no negative impact on remission in patients with chronic myeloid leukemia: results of the randomized CML-study IV. Blood. 2013;122:91. DOI: https://doi.org/10.1182/blood.V122.21.91.91
52. Breccia M, Molica M, Colafigli G, et al. Correlation between Charlson comorbidity index and outcome in patients with chronic phase chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors upfront. Leuk Lymphoma. 2015;56(7):2206–20. doi: 10.3109/10428194.2014.993391. DOI: https://doi.org/10.3109/10428194.2014.993391
53. Iurlo A, Ubertis A, Artuso S, et al. Comorbidities and polypharmacy impact on complete cytogenetic response in chronic myeloid leukaemia elderly patients. Eur J Int Med. 2014;25(1):63–6. doi: 10.1016/j.ejim.2013.11.002. DOI: https://doi.org/10.1016/j.ejim.2013.11.002
54. Common Terminology Criteria for Adverse Events (CTCAE 3) Version 3.0 12.12.2003. [Internet] Available from: http://www.hovon.nl/upload/File/Studies_AlgStudInfo_HovonRichtlijnenDocs/CTCAE_v3.0_12dec03.pdf. (accessed 13.03.2017).
55. Hays RD, Sherbourne CD, Mazel RM. User’s Manual for Medical Outcomes Study (MOS) Core measures of health-related quality of life. RAND; 1995 [Internet] Available from: http://www.rand.org/pubs/monograph_reports/MR162.html. (accessed 13.03.2017).
56. Novik AA, Ionova TI, Kishtovich AV, et al. Stratification of patients using QoL parameters by the method of integral profiles. Qual Life Res. 2003;12(7):770.
57. Nikitina TP, Fedorenko DA, Kurbatova KA, et al. Comprehensive symptom profile in patients with chronic myeloid leukemia: practicability and sensitivity of the new symptom assessment tool CSP Leuk-CML. Haematologica. 2014;(Suppl):B1674.
58. Ионова Т.И., Федоренко Д.А., Никитина Т.П., Курбатова К.А. Качество жизни и профиль симптомов у больных хроническим миелолейкозом на фоне второй линии дазатинибом при непереносимости и резистентности к иматинибу. Клиническая онкогематология. 2013;6(2):166–75. DOI: https://doi.org/10.21320/2500-2139-2013-6-2-166-176
59. [Ionova TI, Fedorenko DA, Nikitina TP, Kurbatova KA. Quality of life and symptom profile in patients with chronic myeloid leukemia receiving dasatinib as а second-line therapy due to intolerance or resistance to imatinib. Klinicheskaya onkogematologiya. 2013;6(2):166–75. (In Russ)]
60. Cortes JE, Hochhaus A, Kim D-W, et al. Four-Year (Yr) Follow-Up Of Patients (Pts) With Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase (CML-CP) Receiving Dasatinib Or Imatinib: Efficacy Based On Early Response. Blood. 2013;122:Abstract 653. DOI: https://doi.org/10.1182/blood.V122.21.653.653
61. Labeit AM, Copland M, Cork LM, et al. Assessment of Quality of Life in the NCRI Spirit 2 Study Comparing Imatinib with Dasatinib in Patients with Newly-Diagnosed Chronic Phase Chronic Myeloid Leukaemia. Blood. 2015;126(23):4024. DOI: https://doi.org/10.1182/blood.V126.23.4024.4024