Альманах клинической медицины. 2015; : 60-65
ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ ТАРГЕТНОЙ ТЕРАПИИ ПАЦИЕНТОВ С ХРОНИЧЕСКИМ МИЕЛОЛЕЙКОЗОМ ИНГИБИТОРАМИ ТИРОЗИНКИНАЗ 1-Й И 2-Й ЛИНИЙ
https://doi.org/10.18786/2072-0505-2015-41-60-65Аннотация
Цель – оценка эффективности лечения ингибиторами тирозинкиназ 1-й и 2-й линий неселективной группы пациентов с хроническим миелолейкозом в реальной клинической практике по отдаленным результатам.
Материал и методы. В научную оценку включены отдаленные результаты проспективного одноцентрового сравнительного клинического исследования с использованием неселективного принципа формирования групп из 116 исследуемых больных хроническим миелолейкозом в различных фазах, получающих ингибитор тирозинкиназ 1-го поколения иматиниб, и из 44 пациентов, находящихся на терапии ингибитором тирозинкиназ 2-го поколения нилотинибом. Анализировали показатели общей выживаемости, беспрогрессивной выживаемости за период с апреля 2005 по апрель 2013 ; медиана наблюдения составила 128 месяцев.
Результаты. Медиана общей выживаемости 116 больных хроническим миелолейкозом, получающих терапию иматинибом, исчисляемая методом Каплана – Мейера, составила 120 месяцев. У 44 пациентов в ранней хронической фазе 5-летняя общая и беспрогрессивная выживаемость отмечена в 93,2% случаев, 8-летняя общая и беспрогрессивная выживаемость – 79,5%. У 44 пациентов в поздней хронической фазе 5-летняя общая и беспрогрессивная выживаемость была 95,5%, 8-летняя общая и беспрогрессивная выживаемость – 72,7%. У 28 больных в фазе акселерации 5-летняя общая выживаемость составила 78,6%, 8-летняя общая выживаемость – 46%. Медиана общей выживаемости пациентов, находящихся на лечении нилотинибом, не достигнута. В течение 78,6 месяца комплексного лечения препаратами общего цитостатического действия, ингибиторами тирозинкиназ 1-й (иматинибом) и 2-й (нилотинибом) линий общая выживаемость составила 100%.
Заключение. Включение больных хроническим миелолейкозом с резистентностью к иматинибу (рецидивом заболевания) либо непереносимостью иматиниба в программу лечения хронического миелолейкоза на первом этапе препаратами общего цитостатического действия, затем ингибиторами тирозинкиназ 1-й и 2-й линий существенно увеличивает общую выживаемость больных в клинической практике.
Список литературы
1. Cortes J, Talpaz M, O'Brien S, Jones D, Luthra R, Shan J, Giles F, Faderl S, Verstovsek S, Garcia-Manero G, Rios MB, Kantarjian H. Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin Cancer Res. 2005;11(9):3425–32.
2. Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, Baccarani M, Cortes J, Cross NC, Druker BJ, Gabert J, Grimwade D, Hehlmann R, Kamel-Reid S, Lipton JH, Longtine J, Martinelli G, Saglio G, Soverini S, Stock W, Goldman JM. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108(1):28–37.
3. Kantarjian HM, O'Brien S, Cortes JE, Smith TL, Rios MB, Shan J, Yang Y, Giles FJ, Thomas DA, Faderl S, Garcia-Manero G, Jeha S, Wierda W, Issa JP, Kornblau SM, Keating M, Resta D, Capdeville R, Talpaz M. Treatment of philadelphia chromosome-positive, accelerated-phase chronic myelogenous leukemia with imatinib mesylate. Clin Cancer Res. 2002;8(7):2167–76.
4. Lahaye T, Riehm B, Berger U, Paschka P, Müller MC, Kreil S, Merx K, Schwindel U, Schoch C, Hehlmann R, Hochhaus A. Response and resistance in 300 patients with BCR-ABL-positive leukemias treated with imatinib in a single center: a 4.5-year follow-up. Cancer. 2005;103(8):1659–69.
5. Ross DM, Branford S, Moore S, Hughes TP. Limited clinical value of regular bone marrow cytogenetic analysis in imatinib-treated chronic phase CML patients monitored by RQ-PCR for BCR-ABL. Leukemia. 2006;20(4):664–70.
6. Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM, Cervantes F, Hochhaus A, Powell BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, Hughes T, Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP, Simonsson B, Taylor K, Baccarani M, So C, Letvak L, Larson RA; IRIS Investigators. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355(23):2408–17.
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8. Giles FJ, le Coutre PD, Pinilla-Ibarz J, Larson RA, Gattermann N, Ottmann OG, Hochhaus A, Radich JP, Saglio G, Hughes TP, Martinelli G, Kim DW, Novick S, Gillis K, Fan X, Cortes J, Baccarani M, Kantarjian HM. Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study. Leukemia. 2013;27(1):107–12. doi: 10.1038/leu.2012.181.
9. ARIAD Pharma Reports Approval Of Iclusig In Canada – Quick Facts. Accessed: 4/6/2015 7:46 AM ET. Available from: http://cml-stop. ru/,http://www.ariad.com, http://www.iclusig. com
10. Vysotskaya L, Golenkov A, Trifonova E, Chernykh Y, Lutskaya Т, Inyutkina N, Chucavina M. Efficacy of the expanded treatment program with imatinib mesylate in 109 patients with chronic myeloid leukemia (CML). Haematologica. 2007;92(Suppl 1):532. Abstr. 1496.
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16. Golenkov AK, Vysotskaya LL, Tryphonova EV, Mytyna TA, Lutskaya TD, Chernyh UB, Kataeva EB, Dudina GA, Buravtsova IV. Сytogenetic response in correlation with imatinib median daily dose in non-selected patients with chronic myeloid leukemia (CML) receiving imatinib in routine practice. ELN Frontiers Meeting 2012. Myeloid Neoplasms: Approaching cure. Istanbul, Turkey, 9–11 November 2012. Abstr. 9. p. 10. Available from: http://www.leukemia-net. org/content/home/eln_meetings/eln_frontiers_meeting/e10295/infoboxContent10296/ ELN_Abstracts_2012.pdf
17. Vysotskaya LL, Golenkov AK, Triphonova EV, Mitina EV, Lutskaya TD, Chernyh UB, Kataeva EB, Dudina GA. Intermittent imatinib therapy in patients with chronic myeloid leukemia is the real basis of routine clinical practice. Abstracts of ELN Frontiers Meeting 2014. Berlin, Germany, 16–19 October 2014. p. 26. Abstract 29. Available from: http://www.leukemia-net.org/content/home/eln_meetings/ eln_frontiers_meeting/e10501/infoboxContent10502/NORE1401ELNFrontiers2014AbstractbookletPP2.pdf
18. Vysotskaya L, Golenkov A, Tryphonova E, Mitina T, Lutskaya T, Chernyh Y, Kataeva E, Dudina G. Efficacy of intermittent imatinib therapy in patients with chronic myeloid leukemia is the real basis of routine clinical practice. 36th EORTC-Pamm Meeting. Marseille, France, 21–24 January 2015. Bioguided Oncology, 2015;33:111.
19. Высоцкая ЛЛ, Голенков АК, Трифонова ЕВ, Митина ТА, Луцкая ТД, Катаева ЕВ, Дудина ГА, Захаров СГ, Буравцова ИВ, Черных ЮБ, Белоусов КА. Эффективность ингибитора тирозинкиназ второй линии в лечении маркерно-рецидивных/резистентных хронических миелолейкозов. В: Материалы XXII конгресса «Человек и лекарство». Москва, Россия, 6–10 апреля 2015 М.; 2015. с. 30.
Almanac of Clinical Medicine. 2015; : 60-65
LONG-TERM RESULTS OF TARGET THERAPY WITH FIRST AND * SECOND-LINE TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA
https://doi.org/10.18786/2072-0505-2015-41-60-65Abstract
Aim: To assess long-term efficacy of firstand second-line tyrosine kinase inhibitors in non-selected patients with chronic myeloid leukemia in a real-life clinical setting.
Materials and methods: The assessment is based on long-term results of a prospective single center comparative clinical trial that was based on non-selected groups of 116 patients with various stages of chronic myeloid leukemia being treated with a first generation tyrosine kinase inhibitor imatinib, and of 44 patients being treated with a second generation tyrosine kinase inhibitor nilotinib. We analyzed all-cause mortality, progression-free survival from April 2005 to April 2013, with a median of the follow-up of 128 months.
Results: In 116 patients with chronic myeloid leukemia treated with imatinib, the Kaplan-Meier survival estimate was 120 months. In 44 patients at an early chronic phase, 5-year overall survival and progression-free survival was 93.2% and 8-year overall and progression-free survival was 79.5%. In 44 patients at a late chronic stage, 5-year overall and progression-free survival was 95.5%, 8-year overall and progression-free survival, 72.7%. In 28 patients at acceleration phase, 5-years overall survival was 78.6% and 8-year overall survival, 46%. Median of overall survival in patients treated with nilotinib was not reached. During 78.6 months of combination treatment with cytotoxic agents, tyrosine kinase inhibitors of the first (imatinib) and second line (nilotinib), overall survival was 100%.
Conclusion: In clinical practice, inclusion of patients with chronic myeloid leukemia and imatinib resistance (disease relapse) or imatinib intolerance into the treatment program with frontline therapy with general cytotoxic agents and thereafter with firstand second-line tyrosine kinase inhibitors significantly improves overall survival.
References
1. Cortes J, Talpaz M, O'Brien S, Jones D, Luthra R, Shan J, Giles F, Faderl S, Verstovsek S, Garcia-Manero G, Rios MB, Kantarjian H. Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate. Clin Cancer Res. 2005;11(9):3425–32.
2. Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, Baccarani M, Cortes J, Cross NC, Druker BJ, Gabert J, Grimwade D, Hehlmann R, Kamel-Reid S, Lipton JH, Longtine J, Martinelli G, Saglio G, Soverini S, Stock W, Goldman JM. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006;108(1):28–37.
3. Kantarjian HM, O'Brien S, Cortes JE, Smith TL, Rios MB, Shan J, Yang Y, Giles FJ, Thomas DA, Faderl S, Garcia-Manero G, Jeha S, Wierda W, Issa JP, Kornblau SM, Keating M, Resta D, Capdeville R, Talpaz M. Treatment of philadelphia chromosome-positive, accelerated-phase chronic myelogenous leukemia with imatinib mesylate. Clin Cancer Res. 2002;8(7):2167–76.
4. Lahaye T, Riehm B, Berger U, Paschka P, Müller MC, Kreil S, Merx K, Schwindel U, Schoch C, Hehlmann R, Hochhaus A. Response and resistance in 300 patients with BCR-ABL-positive leukemias treated with imatinib in a single center: a 4.5-year follow-up. Cancer. 2005;103(8):1659–69.
5. Ross DM, Branford S, Moore S, Hughes TP. Limited clinical value of regular bone marrow cytogenetic analysis in imatinib-treated chronic phase CML patients monitored by RQ-PCR for BCR-ABL. Leukemia. 2006;20(4):664–70.
6. Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM, Cervantes F, Hochhaus A, Powell BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, Hughes T, Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP, Simonsson B, Taylor K, Baccarani M, So C, Letvak L, Larson RA; IRIS Investigators. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355(23):2408–17.
7. Larson RA, Kim DW, Issaragrilsil S, le Coutre P, Dorlhiac-Llacer PE, Etienne G, Clark RE, Flinn I, Nakamae H, Hochhaus A, Saglio G, Kantarjian HM, Donohue B, Deng W, Menssen HD, Hughes TP. Efficacy and safety of nilotinib vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase: long-term follow-up of ENESTnd [abstract]. Blood. 2014;124(21):4541.
8. Giles FJ, le Coutre PD, Pinilla-Ibarz J, Larson RA, Gattermann N, Ottmann OG, Hochhaus A, Radich JP, Saglio G, Hughes TP, Martinelli G, Kim DW, Novick S, Gillis K, Fan X, Cortes J, Baccarani M, Kantarjian HM. Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study. Leukemia. 2013;27(1):107–12. doi: 10.1038/leu.2012.181.
9. ARIAD Pharma Reports Approval Of Iclusig In Canada – Quick Facts. Accessed: 4/6/2015 7:46 AM ET. Available from: http://cml-stop. ru/,http://www.ariad.com, http://www.iclusig. com
10. Vysotskaya L, Golenkov A, Trifonova E, Chernykh Y, Lutskaya T, Inyutkina N, Chucavina M. Efficacy of the expanded treatment program with imatinib mesylate in 109 patients with chronic myeloid leukemia (CML). Haematologica. 2007;92(Suppl 1):532. Abstr. 1496.
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15. Golenkov AK, Vysotskaya LL, Trifonova EV, Mitina TA, Lutskaya TD, Kataeva EV, Dudina GA, Chernykh YuB, Buravtsova IV, Gurov AN, Gorenkov RV. Effektivnost' lecheniya bol'nykh khronicheskim mieloleikozom imatinibom v shirokoi klinicheskoi praktike. Onkogematologiya. 2012;(3):17–21.
16. Golenkov AK, Vysotskaya LL, Tryphonova EV, Mytyna TA, Lutskaya TD, Chernyh UB, Kataeva EB, Dudina GA, Buravtsova IV. Sytogenetic response in correlation with imatinib median daily dose in non-selected patients with chronic myeloid leukemia (CML) receiving imatinib in routine practice. ELN Frontiers Meeting 2012. Myeloid Neoplasms: Approaching cure. Istanbul, Turkey, 9–11 November 2012. Abstr. 9. p. 10. Available from: http://www.leukemia-net. org/content/home/eln_meetings/eln_frontiers_meeting/e10295/infoboxContent10296/ ELN_Abstracts_2012.pdf
17. Vysotskaya LL, Golenkov AK, Triphonova EV, Mitina EV, Lutskaya TD, Chernyh UB, Kataeva EB, Dudina GA. Intermittent imatinib therapy in patients with chronic myeloid leukemia is the real basis of routine clinical practice. Abstracts of ELN Frontiers Meeting 2014. Berlin, Germany, 16–19 October 2014. p. 26. Abstract 29. Available from: http://www.leukemia-net.org/content/home/eln_meetings/ eln_frontiers_meeting/e10501/infoboxContent10502/NORE1401ELNFrontiers2014AbstractbookletPP2.pdf
18. Vysotskaya L, Golenkov A, Tryphonova E, Mitina T, Lutskaya T, Chernyh Y, Kataeva E, Dudina G. Efficacy of intermittent imatinib therapy in patients with chronic myeloid leukemia is the real basis of routine clinical practice. 36th EORTC-Pamm Meeting. Marseille, France, 21–24 January 2015. Bioguided Oncology, 2015;33:111.
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