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Синдром отмены после прекращения терапии ингибиторами тирозинкиназ у больных хроническим миелолейкозом
Синдром отмены после прекращения терапии ингибиторами тирозинкиназ у больных хроническим миелолейкозом
Челышева Е.Ю., Петрова А.Н., Шухов О.А., Быкова А.В., Немченко И.С., Гурьянова М.А., Цыба Н.Н., Туркина А.Г. Синдром отмены после прекращения терапии ингибиторами тирозинкиназ у больных хроническим миелолейкозом. Терапевтический архив. 2022;94(7):836–843. DOI: 10.26442/00403660.2022.07.201747
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Аннотация
Обоснование. Синдром отмены (СО) после прекращения приема ингибиторов тирозинкиназ (ИТК) у пациентов с хроническим миелоидным лейкозом (ХМЛ) описан в исследованиях ремиссии без лечения (РБЛ). Патофизиологические механизмы и факторы развития СО точно не установлены.
Цель. Определить клинические особенности СО и факторы его развития у больных ХМЛ после отмены терапии ИТК в российской когорте пациентов.
Материалы и методы. Анализ выполнен в группе 183 больных ХМЛ со стабильным большим молекулярным ответом (БМО). СО определяли как впервые возникший после отмены ИТК скелетно-мышечный болевой синдром или увеличение степени выраженности ранее имевшихся симптомов.
Результаты. Выживаемость без потери БМО через 36 мес после отмены ИТК составила 49 и 43% в проспективной и ретроспективной группах пациентов соответственно (p=0,96) при медиане (Me) наблюдения 33 (от 1 до 136) мес. СО наблюдался у 49 (27%) больных: 1–2-й степени – у 45 (92%) человек, 3-й степени – у 4 (8%) пациентов. Ме времени до появления СО составила 2 (от 1 до 7) мес, Ме длительности СО – 5 (от 1 до 35) мес. После возобновления терапии в связи с молекулярным рецидивом СО полностью разрешился у 14 из 15 пациентов в течение 1–3 мес, выраженность проявлений уменьшилась у 1 пациента. СО полностью разрешился у 31 из 34 пациентов с продолжением наблюдения в РБЛ; у 3 больных уменьшилась выраженность его симптомов. СО купировался самостоятельно либо на фоне применения нестероидных противовоспалительных препаратов у 14 (45%) и 17 (55%) пациентов соответственно. У больных с СО статистически значимо чаще отмечены более старший возраст (р<0,0001), длительный срок терапии ИТК (р<0,0001) и наличие заболеваний опорно-двигательного аппарата (р=0,022). Развитие СО не зарегистрировано у беременных пациенток (p<0,001). Выживаемость без потери БМО к 12 мес без терапии составила 66 и 42% в группах больных с наличием СО и без него соответственно (р=0,095).
Заключение. Доля больных ХМЛ с СО после отмены ИТК составила 27%, что сопоставимо с данными других исследователей по наблюдению в РБЛ. Более длительный период терапии ИТК, старший возраст и наличие заболеваний опорно-двигательного аппарата ассоциированы с развитием СО. Впервые отмечено, что развитие СО не характерно для пациенток с беременностью. Взаимосвязи между развитием СО и молекулярными рецидивами не установлено.
Ключевые слова: хронический миелолейкоз, большой молекулярный ответ, ремиссия без лечения, синдром отмены
Aim. Our aim was to evaluate clinical features and factors associated with WS in the Russian cohort of CML patients who discontinued TKI therapy.
Materials and methods. WS was evaluated in total of 183 CML patients with chronic phase and sustained deep molecular response (DMR). WS was defined as a musculoskeletal pain newly observed after TKI cessation or as a worsening of previously observed symptoms.
Results. DMR loss free survival at 36 months was 49% and 43% in prospective and retrospective groups respectively (p=0.96) with mеdian (Me) time of observation 33 months (range 1–136). WS was observed in 49 (27%) patients: grade 1–2 was in 45 (92%) patients, grade 3 – in 4 (8%) patients. Me time to WS occurrence was 2 months (range 1–7), Ме duration of WS was 5 months (range 1–35). WS was resolved in 14 of 15 patients with molecular relapse after 1–3 months of TKI re-initiation and was decreased in 1 patient. WS was completely resolved in 31 of 34 patients who continued remained in TFR and decreased in 3 patients. WS was resolved spontaneously or with nonsteroidal anti-inflammatory drugs in 14 (45%) and 17 (55%) patients accordingly. Older age (p<0.0001), longer duration of TKI therapy (p<0.0001) and presence of locomotion system diseases (p=0.022) were observed in patients with WS. No WS was observed in pregnant patients (р<0.001). Survival without DMR loss at 12 months after TKI stop was 66 and 42% in patients with and without WS accordingly (р=0.095).
Conclusion. The rate of WS was 27% that is in a good concordance with the data of the other TFR studies. A longer period of TKI exposure, older age and the history of locomotion system diseases were associated with the development of the WS. We found for the first time that WS was not observed in patients with pregnancy. There was no association of WS development and the rate of molecular relapses.
Keywords: сhronic myeloid leukemia, deep molecular response, treatment free remission, withdrawal syndrome
Цель. Определить клинические особенности СО и факторы его развития у больных ХМЛ после отмены терапии ИТК в российской когорте пациентов.
Материалы и методы. Анализ выполнен в группе 183 больных ХМЛ со стабильным большим молекулярным ответом (БМО). СО определяли как впервые возникший после отмены ИТК скелетно-мышечный болевой синдром или увеличение степени выраженности ранее имевшихся симптомов.
Результаты. Выживаемость без потери БМО через 36 мес после отмены ИТК составила 49 и 43% в проспективной и ретроспективной группах пациентов соответственно (p=0,96) при медиане (Me) наблюдения 33 (от 1 до 136) мес. СО наблюдался у 49 (27%) больных: 1–2-й степени – у 45 (92%) человек, 3-й степени – у 4 (8%) пациентов. Ме времени до появления СО составила 2 (от 1 до 7) мес, Ме длительности СО – 5 (от 1 до 35) мес. После возобновления терапии в связи с молекулярным рецидивом СО полностью разрешился у 14 из 15 пациентов в течение 1–3 мес, выраженность проявлений уменьшилась у 1 пациента. СО полностью разрешился у 31 из 34 пациентов с продолжением наблюдения в РБЛ; у 3 больных уменьшилась выраженность его симптомов. СО купировался самостоятельно либо на фоне применения нестероидных противовоспалительных препаратов у 14 (45%) и 17 (55%) пациентов соответственно. У больных с СО статистически значимо чаще отмечены более старший возраст (р<0,0001), длительный срок терапии ИТК (р<0,0001) и наличие заболеваний опорно-двигательного аппарата (р=0,022). Развитие СО не зарегистрировано у беременных пациенток (p<0,001). Выживаемость без потери БМО к 12 мес без терапии составила 66 и 42% в группах больных с наличием СО и без него соответственно (р=0,095).
Заключение. Доля больных ХМЛ с СО после отмены ИТК составила 27%, что сопоставимо с данными других исследователей по наблюдению в РБЛ. Более длительный период терапии ИТК, старший возраст и наличие заболеваний опорно-двигательного аппарата ассоциированы с развитием СО. Впервые отмечено, что развитие СО не характерно для пациенток с беременностью. Взаимосвязи между развитием СО и молекулярными рецидивами не установлено.
Ключевые слова: хронический миелолейкоз, большой молекулярный ответ, ремиссия без лечения, синдром отмены
________________________________________________
Aim. Our aim was to evaluate clinical features and factors associated with WS in the Russian cohort of CML patients who discontinued TKI therapy.
Materials and methods. WS was evaluated in total of 183 CML patients with chronic phase and sustained deep molecular response (DMR). WS was defined as a musculoskeletal pain newly observed after TKI cessation or as a worsening of previously observed symptoms.
Results. DMR loss free survival at 36 months was 49% and 43% in prospective and retrospective groups respectively (p=0.96) with mеdian (Me) time of observation 33 months (range 1–136). WS was observed in 49 (27%) patients: grade 1–2 was in 45 (92%) patients, grade 3 – in 4 (8%) patients. Me time to WS occurrence was 2 months (range 1–7), Ме duration of WS was 5 months (range 1–35). WS was resolved in 14 of 15 patients with molecular relapse after 1–3 months of TKI re-initiation and was decreased in 1 patient. WS was completely resolved in 31 of 34 patients who continued remained in TFR and decreased in 3 patients. WS was resolved spontaneously or with nonsteroidal anti-inflammatory drugs in 14 (45%) and 17 (55%) patients accordingly. Older age (p<0.0001), longer duration of TKI therapy (p<0.0001) and presence of locomotion system diseases (p=0.022) were observed in patients with WS. No WS was observed in pregnant patients (р<0.001). Survival without DMR loss at 12 months after TKI stop was 66 and 42% in patients with and without WS accordingly (р=0.095).
Conclusion. The rate of WS was 27% that is in a good concordance with the data of the other TFR studies. A longer period of TKI exposure, older age and the history of locomotion system diseases were associated with the development of the WS. We found for the first time that WS was not observed in patients with pregnancy. There was no association of WS development and the rate of molecular relapses.
Keywords: сhronic myeloid leukemia, deep molecular response, treatment free remission, withdrawal syndrome
Полный текст
Список литературы
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18. Kota V, Atallah E. Musculoskeletal Pain in Patients With Chronic Myeloid Leukemia After Tyrosine Kinase Inhibitor Therapy Cessation. Clin Lymphoma Myeloma Leuk. 2019;19(8):480-7. DOI:10.1016/j.clml.2019.05.007
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23. Shah NP, García-Gutiérrez V, Jiménez-Velasco A, et al. Dasatinib discontinuation in patients with chronic-phase chronic myeloid leukemia and stable deep molecular response: the DASFREE study. Leuk Lymphoma. 2019;61(3):650-9. DOI:10.1080/10428194.2019.1675879
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2. Bower H, Björkholm M, Dickman PW, et al. Life Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population. J Clin Oncol. 2016;34(24):2851‑7. DOI:10.1200/jco.2015.66.2866
3. Turkina AG, Novickaja NV, Golenkov AK, et al. Chronic Myeloid Leukemia Patient Registry in the Russian Federation: From Observational Studies to the Efficacy Evaluation in Clinical Practice. Clinical Oncohematology. 2017;10(3):390-401 (in Russian). DOI:10.21320/2500-2139-2017-10-3-390-401
4. Mahon F, Réa D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010;11(11):1029-35. DOI:10.1016/S1470-2045(10)70233-3
5. Ross DM, Branford S, Seymour JF, et al. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013;122(4):515-22. DOI:10.1182/blood-2013-02-483750
6. Saussele S, Richter J, Guilhot J, et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018;19(6):747-57. DOI:10.1016/s1470-2045(18)30192-x
7. Hochhaus A, Masszi T, Giles FJ, et al. Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia. 2017;31(7):1525-31. DOI:10.1038/leu.2017.63
8. Mahon FX, Boquimpani C, Kim DW, et al. Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Single-Group, Phase 2, Open-Label Study. Ann Intern Med. 2018;168(7):461-70. DOI:10.7326/m17-1094
9. Imagawa J, Tanaka H, Okada M, et al. Discontinuation of dasatinib in patients with chronic myeloid leukaemia who have maintained deep molecular response for longer than 1 year (DADI trial): a multicentre phase 2 trial. Lancet Haematol. 2015;2(12):e528-35. DOI:10.1016/s2352-3026(15)00196-9
10. Rea D, Nicolini FE, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2017;129(7):846-54. DOI:10.1182/blood-2016-09-742205
11. Turkina AG, Petrova AN, Chelysheva EYu, et al. A prospective study of the monitoring of patients with chronic myeloid leukemia upon withdrawal of tyrosine kinase inhibitor therapy. Russian Journal of Hematology and Transfusiology. 2020;65(4):370-85 (in Russian). DOI:10.35754/0234-5730-2020-65-4-370-385
12. Hughes TP, Ross DM. Moving treatment-free remission into mainstream clinical practice in CML. Blood. 2016;128(1):17-23. DOI:10.1182/blood-2016-01-694265
13. Laneuville P. When to Stop Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia. Curr Treat Options Oncol. 2018;19(3):15. DOI:10.1007/s11864-018-0532-2
14. Rea D, Cayuela JM. Treatment-free remission in patients with chronic myeloid leukemia. Int J Hematol. 2018;108(4):355-64. DOI:10.1007/s12185-017-2295-0
15. Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966-84.
DOI:10.1038/s41375-020-0776-2
16. Chen KK, Du TF, Xiong PS, et al. Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia With Losing Major Molecular Response as a Definition for Molecular Relapse: A Systematic Review and Meta-Analysis. Front Oncol. 2019;9:372. DOI:10.3389/fonc.2019.00372
17. Park JS, Lee SE, Jeong SH, et al. Change of health-related profiles after Imatinib cessation in chronic phase chronic myeloid leukemia patients. Leuk Lymphoma. 2016;57(2):341-7. DOI:10.3109/10428194.2015.1049166
18. Kota V, Atallah E. Musculoskeletal Pain in Patients With Chronic Myeloid Leukemia After Tyrosine Kinase Inhibitor Therapy Cessation. Clin Lymphoma Myeloma Leuk. 2019;19(8):480-7. DOI:10.1016/j.clml.2019.05.007
19. Richter J, Söderlund S, Lübking A, et al. Musculoskeletal Pain in Patients With Chronic Myeloid Leukemia After Discontinuation of Imatinib: A Tyrosine Kinase Inhibitor Withdrawal Syndrome? J Clin Oncol. 2014;32(25):2821-3. DOI:10.1200/jco.2014.55.6910
20. Lee SE, Choi SY, Song HY, et al. Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study. Haematologica. 2016;101(6):717-23. DOI:10.3324/haematol.2015.139899
21. Katagiri S, Tauchi T, Ando K, et al. Low body weight and body mass index may be associated with musculoskeletal pain following imatinib discontinuation in chronic myeloid leukemia. Leuk Res Rep. 2017;7:33‑5. DOI:10.1016/j.lrr.2017.04.002
22. Berger MG, Pereira B, Rousselot P, et al. Longer treatment duration and history of osteoarticular symptoms predispose to tyrosine kinase inhibitor withdrawal syndrome. Br J Haematol. 2019;187(3):337-46. DOI:10.1111/bjh.16083
23. Shah NP, García-Gutiérrez V, Jiménez-Velasco A, et al. Dasatinib discontinuation in patients with chronic-phase chronic myeloid leukemia and stable deep molecular response: the DASFREE study. Leuk Lymphoma. 2019;61(3):650-9. DOI:10.1080/10428194.2019.1675879
24. Buchdunger E, Cioffi CL, Law N, et al. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther. 2000;295(1):139-45.
25. Galimberti S, Fontanelli G, Barsotti S, et al. Increased values of the circulating PDGFβ sustains the "withdrawal syndrome" after tyrosine kinase inhibitor discontinuation in patients affected by chronic myeloid leukemia. Blood Cells Mol Dis. 2015;55(3):211-2. DOI:10.1016/j.bcmd.2015.06.010
26. Takahashi N, Nishiwaki K, Nakaseko C, et al. Treatment-free remission after two-year consolidation therapy with nilotinib in patients with chronic myeloid leukemia: STAT2 trial in Japan. Haematologica. 2018;103(11):1835-42. DOI:10.3324/haematol.2018.194894
27. Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0, 2009. Available at: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed: 11.07.2022.
28. Petinati NA, Petrova AN, Chelysheva EY, et al. Multipotent Mesenchymal Stromal Cells in Patients with Chronic Myeloid Leukemia before Discontinuation of Tyrosine Kinase Inhibitors. Bull Exp Biol Med. 2019;167(4):580-3. DOI:10.1007/s10517-019-04575-0
29. Petrova A, Chelysheva E, Shukhov O, et al. Withdrawal Syndrome After Tyrosine Kinase Inhibitor Discontinuation in Patients With Chronic Myeloid Leukemia in the Russian Prospective Study RU-SKI. Clin Lymphoma Myeloma Leuk. 2020;20(5):267-71. DOI:10.1016/j.clml.2019.12.019
30. Radich JP, Deininger M, Abboud CN, et al. Chronic Myeloid Leukemia, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018;16(9):1108-35. DOI:10.6004/jnccn.2018.0071
31. Рубрикатор клинических рекомендаций. Режим доступа: http://cr.rosminzdrav.ru/#!/recomend/120. Ссылка активна на 11.07.2022 [Rubrikator klinicheskikh rekomendatsii. Available at: http://cr.rosminzdrav.ru/#!/recomend/120. Accessed: 11.07.2022 (in Russian)].
2. Bower H, Björkholm M, Dickman PW, et al. Life Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population. J Clin Oncol. 2016;34(24):2851‑7. DOI:10.1200/jco.2015.66.2866
3. Туркина А.Г., Новицкая Н.В., Голенков А.К., и др. Регистр больных хроническим миелолейкозом в Российской Федерации: от наблюдательного исследования к оценке эффективности терапии в клинической практике. Клиническая онкогематология. 2017;10(3):390-401 [Turkina AG, Novickaja NV, Golenkov AK, et al. Chronic Myeloid Leukemia Patient Registry in the Russian Federation: From Observational Studies to the Efficacy Evaluation in Clinical Practice. Clinical Oncohematology. 2017;10(3):390-401 (in Russian)]. DOI:10.21320/2500-2139-2017-10-3-390-401
4. Mahon F, Réa D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010;11(11):1029-35. DOI:10.1016/S1470-2045(10)70233-3
5. Ross DM, Branford S, Seymour JF, et al. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013;122(4):515-22. DOI:10.1182/blood-2013-02-483750
6. Saussele S, Richter J, Guilhot J, et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018;19(6):747-57. DOI:10.1016/s1470-2045(18)30192-x
7. Hochhaus A, Masszi T, Giles FJ, et al. Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia. 2017;31(7):1525-31. DOI:10.1038/leu.2017.63
8. Mahon FX, Boquimpani C, Kim DW, et al. Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Single-Group, Phase 2, Open-Label Study. Ann Intern Med. 2018;168(7):461-70. DOI:10.7326/m17-1094
9. Imagawa J, Tanaka H, Okada M, et al. Discontinuation of dasatinib in patients with chronic myeloid leukaemia who have maintained deep molecular response for longer than 1 year (DADI trial): a multicentre phase 2 trial. Lancet Haematol. 2015;2(12):e528-35. DOI:10.1016/s2352-3026(15)00196-9
10. Rea D, Nicolini FE, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2017;129(7):846-54. DOI:10.1182/blood-2016-09-742205
11. Туркина А.Г., Петрова А.Н., Челышева Е.Ю., и др. Результаты проспективного исследования по наблюдению больных хроническим миелолейкозом после прекращения терапии ингибиторами тирозинкиназ. Гематология и трансфузиология. 2020;65(4):370‑85 [Turkina AG, Petrova AN, Chelysheva EYu, et al. A prospective study of the monitoring of patients with chronic myeloid leukemia upon withdrawal of tyrosine kinase inhibitor therapy. Russian Journal of Hematology and Transfusiology. 2020;65(4):370-85 (in Russian)]. DOI:10.35754/0234-5730-2020-65-4-370-385
12. Hughes TP, Ross DM. Moving treatment-free remission into mainstream clinical practice in CML. Blood. 2016;128(1):17-23. DOI:10.1182/blood-2016-01-694265
13. Laneuville P. When to Stop Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia. Curr Treat Options Oncol. 2018;19(3):15. DOI:10.1007/s11864-018-0532-2
14. Rea D, Cayuela JM. Treatment-free remission in patients with chronic myeloid leukemia. Int J Hematol. 2018;108(4):355-64. DOI:10.1007/s12185-017-2295-0
15. Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966-84.
DOI:10.1038/s41375-020-0776-2
16. Chen KK, Du TF, Xiong PS, et al. Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia With Losing Major Molecular Response as a Definition for Molecular Relapse: A Systematic Review and Meta-Analysis. Front Oncol. 2019;9:372. DOI:10.3389/fonc.2019.00372
17. Park JS, Lee SE, Jeong SH, et al. Change of health-related profiles after Imatinib cessation in chronic phase chronic myeloid leukemia patients. Leuk Lymphoma. 2016;57(2):341-7. DOI:10.3109/10428194.2015.1049166
18. Kota V, Atallah E. Musculoskeletal Pain in Patients With Chronic Myeloid Leukemia After Tyrosine Kinase Inhibitor Therapy Cessation. Clin Lymphoma Myeloma Leuk. 2019;19(8):480-7. DOI:10.1016/j.clml.2019.05.007
19. Richter J, Söderlund S, Lübking A, et al. Musculoskeletal Pain in Patients With Chronic Myeloid Leukemia After Discontinuation of Imatinib: A Tyrosine Kinase Inhibitor Withdrawal Syndrome? J Clin Oncol. 2014;32(25):2821-3. DOI:10.1200/jco.2014.55.6910
20. Lee SE, Choi SY, Song HY, et al. Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study. Haematologica. 2016;101(6):717-23. DOI:10.3324/haematol.2015.139899
21. Katagiri S, Tauchi T, Ando K, et al. Low body weight and body mass index may be associated with musculoskeletal pain following imatinib discontinuation in chronic myeloid leukemia. Leuk Res Rep. 2017;7:33‑5. DOI:10.1016/j.lrr.2017.04.002
22. Berger MG, Pereira B, Rousselot P, et al. Longer treatment duration and history of osteoarticular symptoms predispose to tyrosine kinase inhibitor withdrawal syndrome. Br J Haematol. 2019;187(3):337-46. DOI:10.1111/bjh.16083
23. Shah NP, García-Gutiérrez V, Jiménez-Velasco A, et al. Dasatinib discontinuation in patients with chronic-phase chronic myeloid leukemia and stable deep molecular response: the DASFREE study. Leuk Lymphoma. 2019;61(3):650-9. DOI:10.1080/10428194.2019.1675879
24. Buchdunger E, Cioffi CL, Law N, et al. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther. 2000;295(1):139-45.
25. Galimberti S, Fontanelli G, Barsotti S, et al. Increased values of the circulating PDGFβ sustains the "withdrawal syndrome" after tyrosine kinase inhibitor discontinuation in patients affected by chronic myeloid leukemia. Blood Cells Mol Dis. 2015;55(3):211-2. DOI:10.1016/j.bcmd.2015.06.010
26. Takahashi N, Nishiwaki K, Nakaseko C, et al. Treatment-free remission after two-year consolidation therapy with nilotinib in patients with chronic myeloid leukemia: STAT2 trial in Japan. Haematologica. 2018;103(11):1835-42. DOI:10.3324/haematol.2018.194894
27. Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0, 2009. Available at: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed: 11.07.2022.
28. Petinati NA, Petrova AN, Chelysheva EY, et al. Multipotent Mesenchymal Stromal Cells in Patients with Chronic Myeloid Leukemia before Discontinuation of Tyrosine Kinase Inhibitors. Bull Exp Biol Med. 2019;167(4):580-3. DOI:10.1007/s10517-019-04575-0
29. Petrova A, Chelysheva E, Shukhov O, et al. Withdrawal Syndrome After Tyrosine Kinase Inhibitor Discontinuation in Patients With Chronic Myeloid Leukemia in the Russian Prospective Study RU-SKI. Clin Lymphoma Myeloma Leuk. 2020;20(5):267-71. DOI:10.1016/j.clml.2019.12.019
30. Radich JP, Deininger M, Abboud CN, et al. Chronic Myeloid Leukemia, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018;16(9):1108-35. DOI:10.6004/jnccn.2018.0071
31. Рубрикатор клинических рекомендаций. Режим доступа: http://cr.rosminzdrav.ru/#!/recomend/120. Ссылка активна на 11.07.2022 [Rubrikator klinicheskikh rekomendatsii. Available at: http://cr.rosminzdrav.ru/#!/recomend/120. Accessed: 11.07.2022 (in Russian)].
________________________________________________
2. Bower H, Björkholm M, Dickman PW, et al. Life Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population. J Clin Oncol. 2016;34(24):2851‑7. DOI:10.1200/jco.2015.66.2866
3. Turkina AG, Novickaja NV, Golenkov AK, et al. Chronic Myeloid Leukemia Patient Registry in the Russian Federation: From Observational Studies to the Efficacy Evaluation in Clinical Practice. Clinical Oncohematology. 2017;10(3):390-401 (in Russian). DOI:10.21320/2500-2139-2017-10-3-390-401
4. Mahon F, Réa D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010;11(11):1029-35. DOI:10.1016/S1470-2045(10)70233-3
5. Ross DM, Branford S, Seymour JF, et al. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013;122(4):515-22. DOI:10.1182/blood-2013-02-483750
6. Saussele S, Richter J, Guilhot J, et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol. 2018;19(6):747-57. DOI:10.1016/s1470-2045(18)30192-x
7. Hochhaus A, Masszi T, Giles FJ, et al. Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia. 2017;31(7):1525-31. DOI:10.1038/leu.2017.63
8. Mahon FX, Boquimpani C, Kim DW, et al. Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Single-Group, Phase 2, Open-Label Study. Ann Intern Med. 2018;168(7):461-70. DOI:10.7326/m17-1094
9. Imagawa J, Tanaka H, Okada M, et al. Discontinuation of dasatinib in patients with chronic myeloid leukaemia who have maintained deep molecular response for longer than 1 year (DADI trial): a multicentre phase 2 trial. Lancet Haematol. 2015;2(12):e528-35. DOI:10.1016/s2352-3026(15)00196-9
10. Rea D, Nicolini FE, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2017;129(7):846-54. DOI:10.1182/blood-2016-09-742205
11. Turkina AG, Petrova AN, Chelysheva EYu, et al. A prospective study of the monitoring of patients with chronic myeloid leukemia upon withdrawal of tyrosine kinase inhibitor therapy. Russian Journal of Hematology and Transfusiology. 2020;65(4):370-85 (in Russian). DOI:10.35754/0234-5730-2020-65-4-370-385
12. Hughes TP, Ross DM. Moving treatment-free remission into mainstream clinical practice in CML. Blood. 2016;128(1):17-23. DOI:10.1182/blood-2016-01-694265
13. Laneuville P. When to Stop Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia. Curr Treat Options Oncol. 2018;19(3):15. DOI:10.1007/s11864-018-0532-2
14. Rea D, Cayuela JM. Treatment-free remission in patients with chronic myeloid leukemia. Int J Hematol. 2018;108(4):355-64. DOI:10.1007/s12185-017-2295-0
15. Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966-84.
DOI:10.1038/s41375-020-0776-2
16. Chen KK, Du TF, Xiong PS, et al. Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia With Losing Major Molecular Response as a Definition for Molecular Relapse: A Systematic Review and Meta-Analysis. Front Oncol. 2019;9:372. DOI:10.3389/fonc.2019.00372
17. Park JS, Lee SE, Jeong SH, et al. Change of health-related profiles after Imatinib cessation in chronic phase chronic myeloid leukemia patients. Leuk Lymphoma. 2016;57(2):341-7. DOI:10.3109/10428194.2015.1049166
18. Kota V, Atallah E. Musculoskeletal Pain in Patients With Chronic Myeloid Leukemia After Tyrosine Kinase Inhibitor Therapy Cessation. Clin Lymphoma Myeloma Leuk. 2019;19(8):480-7. DOI:10.1016/j.clml.2019.05.007
19. Richter J, Söderlund S, Lübking A, et al. Musculoskeletal Pain in Patients With Chronic Myeloid Leukemia After Discontinuation of Imatinib: A Tyrosine Kinase Inhibitor Withdrawal Syndrome? J Clin Oncol. 2014;32(25):2821-3. DOI:10.1200/jco.2014.55.6910
20. Lee SE, Choi SY, Song HY, et al. Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study. Haematologica. 2016;101(6):717-23. DOI:10.3324/haematol.2015.139899
21. Katagiri S, Tauchi T, Ando K, et al. Low body weight and body mass index may be associated with musculoskeletal pain following imatinib discontinuation in chronic myeloid leukemia. Leuk Res Rep. 2017;7:33‑5. DOI:10.1016/j.lrr.2017.04.002
22. Berger MG, Pereira B, Rousselot P, et al. Longer treatment duration and history of osteoarticular symptoms predispose to tyrosine kinase inhibitor withdrawal syndrome. Br J Haematol. 2019;187(3):337-46. DOI:10.1111/bjh.16083
23. Shah NP, García-Gutiérrez V, Jiménez-Velasco A, et al. Dasatinib discontinuation in patients with chronic-phase chronic myeloid leukemia and stable deep molecular response: the DASFREE study. Leuk Lymphoma. 2019;61(3):650-9. DOI:10.1080/10428194.2019.1675879
24. Buchdunger E, Cioffi CL, Law N, et al. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther. 2000;295(1):139-45.
25. Galimberti S, Fontanelli G, Barsotti S, et al. Increased values of the circulating PDGFβ sustains the "withdrawal syndrome" after tyrosine kinase inhibitor discontinuation in patients affected by chronic myeloid leukemia. Blood Cells Mol Dis. 2015;55(3):211-2. DOI:10.1016/j.bcmd.2015.06.010
26. Takahashi N, Nishiwaki K, Nakaseko C, et al. Treatment-free remission after two-year consolidation therapy with nilotinib in patients with chronic myeloid leukemia: STAT2 trial in Japan. Haematologica. 2018;103(11):1835-42. DOI:10.3324/haematol.2018.194894
27. Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0, 2009. Available at: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed: 11.07.2022.
28. Petinati NA, Petrova AN, Chelysheva EY, et al. Multipotent Mesenchymal Stromal Cells in Patients with Chronic Myeloid Leukemia before Discontinuation of Tyrosine Kinase Inhibitors. Bull Exp Biol Med. 2019;167(4):580-3. DOI:10.1007/s10517-019-04575-0
29. Petrova A, Chelysheva E, Shukhov O, et al. Withdrawal Syndrome After Tyrosine Kinase Inhibitor Discontinuation in Patients With Chronic Myeloid Leukemia in the Russian Prospective Study RU-SKI. Clin Lymphoma Myeloma Leuk. 2020;20(5):267-71. DOI:10.1016/j.clml.2019.12.019
30. Radich JP, Deininger M, Abboud CN, et al. Chronic Myeloid Leukemia, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018;16(9):1108-35. DOI:10.6004/jnccn.2018.0071
31. Рубрикатор клинических рекомендаций. Режим доступа: http://cr.rosminzdrav.ru/#!/recomend/120. Ссылка активна на 11.07.2022 [Rubrikator klinicheskikh rekomendatsii. Available at: http://cr.rosminzdrav.ru/#!/recomend/120. Accessed: 11.07.2022 (in Russian)].
Авторы
Е.Ю. Челышева, А.Н. Петрова*, О.А. Шухов, А.В. Быкова, И.С. Немченко, М.А. Гурьянова, Н.Н. Цыба, А.Г. Туркина
ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России, Москва, Россия
*ap996@mail.ru
National Medical Research Center for Hematology, Moscow, Russia
*ap996@mail.ru
ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России, Москва, Россия
*ap996@mail.ru
________________________________________________
National Medical Research Center for Hematology, Moscow, Russia
*ap996@mail.ru
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