Ремиссия без лечения у больных хроническим миелолейкозом: обзор литературы
Аннотация
Терапия ингибиторами тирозинкиназ радикально изменила течение хронического миелолейкоза, значительно повысив выживаемость и снизив риск прогрессирования заболевания. У 50–70 % пациентов удается достичь низкого или неопределяемого уровня минимальной остаточной болезни – глубокого молекулярного ответа. Длительная терапия ингибиторами тирозинкиназ примерно у трети больных сопровождается развитием токсичности и снижает качество жизни, что определяет актуальность вопроса безопасного прекращения лечения. В условиях клинических исследований у больных с длительным глубоким молекулярным ответом показана возможность сохранения ремиссии без лечения примерно в 40–60 % случаев; при этом все пациенты с молекулярным рецидивом вновь достигают ремиссии после возобновления терапии ингибиторами тирозинкиназ. В настоящее время проводится поиск клинических и молекулярногенетических факторов для определения групп пациентов, имеющих наибольшую вероятность сохранения ремиссии без лечения. Предполагается, что прекращение терапии ингибиторами тирозинкиназ может улучшить качество жизни пациентов, однако в 30 % случаев наблюдается синдром отмены, проявляющийся возникновением или ухудшением ранее существующего болевого синдрома в суставах, мышцах и костях. Механизмы развития этого явления на данный момент неясны. Таким образом, многие вопросы, касающиеся ремиссии без лечения, требуют изучения, что определяет важность проведения клинических исследований в этой области.
Об авторах
А. Н. Петрова
ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России
Россия
Россия
Анна Николаевна Петрова
125167 Москва, Новый Зыковский проезд, 4
Е. Ю. Челышева
ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России
Россия
Россия
125167 Москва, Новый Зыковский проезд, 4
А. Г. Туркина
ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России
Россия
Россия
125167 Москва, Новый Зыковский проезд, 4
Список литературы
1. Туркина А.Г., Челышева Е.Ю. Стратегия терапии хронического миелолейкоза: возможности и перспективы. Терапевтический архив 2013;85(7):4–9.
2. Brunner A.M., Campigotto F., Sadrzadeh H. et al. Trends in all-cause mortality among patients with chronic myeloid leukemia: a Surveillance, Epidemiology, and End Results database analysis. Cancer 2013;119 (14):2620–9. DOI: 10.1002/cncr.28106.
3. Sasaki K., Strom S.S., O’Brien S. et al. Relative survival in patients with chronicphase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials. Lancet Haematol 2015;2(5):186–93. DOI: 10.1016/S2352-3026(15)00048-4.
4. Hochhaus A., Larson R.A., Guilhot F. et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med 2017;376(10):917–27. DOI: 10.1056/NEJMoa1609324.
5. Shukhov O., Chelysheva E., Gusarova G. et al. Imatinib treatment in chronic myeloid leukemia patients in early and late chronic phase: current incidence of cytogenetic remission and a very long-term an intention-to-treat analysis. Ferrata Storti Foundation. Proceedings of the 20th Congress of the European Hematology Association. Haematologica 2015;100 (S1):437.
6. Pulte D., Barnes B., Jansen L. et al. Population level survival of patients with chronic myelocytic leukemia in Germany compared to the US in the early 21st century. J Hematol Oncol 2013;6(1):70. DOI: 10.1186/1756-8722-6-70.
7. Huang X., Cortes J., Kantarjian H. Estimations of the increasing prevalence and plateau prevalence of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. Cancer 2012;118(12):3123–7. DOI: 10.1002/cncr.26679.
8. O’Brien S.G., Guilhot F., Larson R.A. et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003;348(11):994– 1004. DOI: 10.1056/NEJMoa022457.
9. Ross D.M., Branford S., Moore S., Hughes T.P. Limited clinical value of regular bone marrow cytogenetic analysis in imatinib-treated chronic phase CML patients monitored by RQ-PCR for BCRABL. Leukemia 2006;20(4):664–70. DOI: 10.1038/sj.leu.2404139.
10. Baccarani M., Deininger M.W., Rosti G. et al. European Leukemia Net recommendations for the management of chronic myeloid leukemia: 2013. Blood 2013;122(6) 872–84. DOI: 10.1182/blood-2013-05-501569.
11. Hochhaus A., Saussele S., Rosti G. et al. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28(suppl_4):41–51. DOI: 10.1093/annonc/mdx219.
12. Туркина А.Г., Зарицкий А.Ю., Шуваев В.А. и др. Клинические рекомендации по диагностике и лечению хронического миелолейкоза. Клиническая онкогематология 2017;10(3):294–316. DOI: 10.21320/2500-2139-2017-10-3294-316.
13. Branford S., Seymour J.F., Grigg A. et al. BCR-ABL messenger RNA levels continue to decline in patients with chronic phase chronic myeloid leukemia treated with imatinib for more than 5 years and approximately half of all first-line treated patients have stable undetectable BCRABL using strict sensitivity criteria. Clin Cancer Res 2007;13(23):7080–5. DOI: 10.1158/1078-0432.CCR-07-0844.
14. Cross N.C., White H.E., Colomer D. et al. Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia. Leukemia 2015;29(5):999–1003. DOI: 10.1038/leu.2015.29.
15. Hochhaus A., Saglio G., Hughes T.P. et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia 2016;30(5):1044–54. DOI: 10.1038/leu.2016.5.
16. Cortes J.E., Saglio G., Kantarjian H.M. et al. Final 5-year study results of DASISION: the dasatinib versus imatinib study in treatment-naïve chronic myeloid leukemia patients trial. J Clin Oncol 2016;34(20):2333–40. DOI: 10.1200/JCO.2015.64.8899.
17. Williams L.A., Garcia Gonzalez A.G., Ault P. et al. Measuring the symptom burden associated with the treatment of chronic myeloid leukemia. Blood 2013;122(5):641–7. DOI: 10.1182/blood-2013-01-477687.
18. Efficace F., Baccarani M., Breccia M. et al. 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.
19. Kantarjian H.M., Shah N.P., Cortes J.E. et al. Dasatinib or imatinib in newly diagnosed chronicphase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood 2012;119(5):1123–9. DOI: 10.1182/blood-2011-08-376087.
20. Chai-Adisaksopha C., Lam W., Hillis C. Major arterial events in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a meta-analysis. Leuk Lymphoma 2016;57(6):1300–10. DOI: 10.3109/10428194.2015.1091929.
21. Yilmaz M., Lahoti A., O’Brien S. et al. Estimated glomerular filtration rate changes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. Cancer 2015;121(21):3894–904. DOI: 10.1002/cncr.29587.
22. Palani R., Milojkovic D., Apperley J.F. Managing pregnancy in chronic myeloid leukemia. Ann Hematol 2015;94:167–76. DOI: 10.1007/s00277-015-2317-z.
23. Saußele S., Richter J., Hochhaus A., Mahon F.X. The concept of treatment-free remission in chronic myeloid leukemia. Leukemia 2016;30:1638–47. DOI: 10.1038/leu.2016.115.
24. Mahon F.X., Delbrel X., Cony-Makhoul P. et al. Follow-up of complete cytogenetic remission in patients with chronic myeloid leukemia after cessation of interferon alfa. J Clin Oncol 2002;20(1):214–20. DOI: 10.1200/JCO.2002.20.1.214.
25. Rousselot P., Huguet F., Rea D. et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood 2007;109(1):58–60. DOI: 10.1182/blood-2006-03-011239.
26. Mahon F.X., Rea 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.
27. Etienne G., Guilhot J., Rea D. et al. Long-term follow-up of the French Stop Imatinib (STIM1) study in patients with chronic myeloid leukemia. J Clin Oncol 2017;35(3):298–305. DOI: 10.1200/JCO.2016.68.2914.
28. Ross D.M., Branford S., Seymour J.F. 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.
29. Rousselot P., Charbonnier A., Cony-Makhoul P. et al. Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. J Clin Oncol 2014;32(5):424–30. DOI: 10.1200/JCO.2012.48.5797.
30. Yhim H.Y., Lee N.R., Song E.K. et al. Imatinib mesylate discontinuation in patients with chronic myeloid leukemia who have received front-line imatinib mesylate therapy and achieved complete molecular response. Leuk Res 2012;36(6):689–93. DOI: 10.1016/j.leukres.2012.02.011.
31. Mahon F.X., Nicolini F.E., Noel M.P. et al. Preliminary report of the STIM2 study: a multicenter stop imatinib trial for chronic phase chronic myeloid leukemia de novo patients on imatinib. American Society of Hematology (ASH). Proceedings of the 55th ASH Annual Meeting. New Orleans, LA. Blood 2013;122(21):Abstract 654.
32. 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, nonrandomised, trial. Lancet Oncol 2018;19(6):747–57. DOI: 10.1016/S14702045(18)30192-X.
33. Hughes T.P., Lipton J.H., Spector N. et al. Deep molecular responses achieved in patients with CML-CP who are switched to nilotinib after longterm imatinib. Blood 2014;124(5):729–36. DOI: 10.1182/blood-2013-12-544015.
34. Hochhaus A., Masszi T., Giles F.J. 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.
35. Mahon F.X., Boquimpani C., Kim D. et al. Treatment-free remission after secondline 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/M171094.
36. 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):528–35. DOI: 10.1016/S23523026(15)00196-9.
37. Rea D., Nicolini F.E., 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.
38. Hughes T.P., Ross D.M. Moving treatmentfree remission into mainstream clinical practice in CML. Blood 2016;128(1):17–23. DOI: 10.1182/blood-2016-01-694265.
39. Kim D., Bence-Bruckler I., Forrest D.L. et al. Interim results of the Canadian Tyrosine Kinase Inhibitor Discontinuation trial for 2nd attempt of treatment free remission: treatment free remission accomplished by dasatinib (TRAD). American Society of Hematology (ASH). Proceedings of the 59th ASH Annual Meeting; Atlanta, GA. Blood 2017;130(1):Abstract 1622.
40. Lee S.E., Choi S.Y., Song H.Y. 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.
41. Mori S., Vagge E., le Coutre P. et al. Age and dPCR can predict relapse in CML patients who discontinued imatinib: the ISAV study. Am J Hematol 2015;90(10):910–4. DOI: 10.1002/ajh.24120.
42. Fava C., Rege-Carmbrin G., Dogliotti I. et al. Observational study of CML Italian patients who discontinued TKIs. American Society of Hematology (ASH). Proceedings of the 59th ASH Annual Meeting; Atlanta, GA. Blood 2017;130(1):Abstract 1616.
43. Туркина А.Г., Челышева Е.Ю., Шуваев В.А. и др. Результаты наблюдения больных хроническим миелолейкозом с глубоким молекулярным ответом без терапии ингибиторами тирозинкиназ. Терапевтический архив 2017;89 (12):86–96. DOI: 10.17116/terarkh201789128696.
44. Legros L., Nicolini F.E., Etienne G. et al. Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic myeloid leukemia. Cancer 2017;123(22): 4403–10. DOI: 10.1002/cncr.30885.
45. Park J.S., Lee S.E., Jeong S.H. 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.
46. Richter J., Soderlund S., Lubking 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.
47. Rea D., Cayuela J.M. Treatment-free remission in patients with chronic myeloid leukemia. Int J Hematol 2018;108(4):355– 64. DOI: 10.1007/s12185-017-2295-0
48. 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.
49. Shah N.P., Gutiérrez J.V.G., JiménezVelasco A. et al. Dasatinib discontinuation in patients (pts) with chronic-phase chronic myeloid leukemia (CML-CP) and stable deep molecular response (DASFREE). American Society of Hematology (ASH). Proceedings of the 59th ASH Annual Meeting; Atlanta, GA. Blood 2017;130(1):Abstract 314.
50. Buchdunger E., Cioffi C.L., 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.
51. Berger M.G., Pereira B., Oris C. et al. Osteoarticular pain after discontinuation of tyrosine kinase inhibitors (TKI): a French cohort. American Society of Hematology (ASH). Proceedings of the 57th ASH Annual Meeting; Orlando, FL. Blood 2015;126(23):Abstract 137.
52. Ионова Т.И., Никитина Т.П., Ломаиа Е.Г. и др. Показатели качества жизни, профиль симптомов и клинический эффект терапии второй линии дазатинибом у больных хроническим миелолейкозом при резистентности или непереносимости предшествующей терапии иматинибом: результаты 2-летнего мониторинга. Онкогематология 2015;10(3):18–27. DOI: 10.17650/1818-8346-2015-10-3-18-27.
53. Mahon X.F. Treatment-free remission in CML: who, how, and why? Hematology. American Society of Hematology. Education Program 2017;(1):102–9. DOI: 10.1182/asheducation-2017.1.102.
54. Mahon X.F., Boquimpani C.M., Takahashi N. et al. Patient-reported quality of life before and after stopping treatment in the ENESTop trial of treatment-free remission for patients with chronic myeloid leukemia in chronic phase. American Society of Hematology (ASH). Proceedings of the 58th ASH Annual Meeting; San Diego, CA. Blood 2016;128(22):Abstract 1891.
55. Breccia M., Efficace F., Sica S. et al. Adherence and future discontinuation of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia: a patient-based survey on 1133 patients. Leuk Res 2015;39(10):1055–9. DOI: 10.1016/j.leukres.2015.07.004.
56. Radich J.P., Deininger M., Abboud C.N. et al. NCCN Clinical practice guidelines in oncology. Chronic Myeloid Leukemia Version I 2019. J Natl Compr Canc Netw 2018;16(9):1108–35. DOI: 10.6004/jnccn.2018.0071.
57. Giona F., Saglio G., Moleti M.L. et al. Treatment-free remission after imatinib discontinuation is possible in paediatric patients with chronic myeloid leukaemia. Br J Haematol 2015;168(2):305–8. DOI: 10.1111/bjh.13103.
58. Millot F., Claviez A., Leverger G. et al. Imatinib cessation in children and adolescents with chronic myeloid leukemia in chronic phase. Pediatr Blood Cancer 2014;61(2):355–7. DOI: 10.1002/pbc.24521.
59. Choeyprasert W., Yansomdet T., Natesirinilkul R. et al. Adverse effects of imatinib in children with chronic myelogenous leukemia. Pediatr Int 2017;59(3):286–92. DOI: 10.1111/ped.13136.
60. Clark R.E., Polydoros F., Apperley J.F. et al. De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial. Lancet Haematol 2017;4(7):310–6. DOI: 10.1016/S23523026(17)30066-2.
61. Ilander M.M., Olsson-Stromberg U., Lahteenmaki H. et al. Early disease relapse after tyrosine kinase inhibitor treatment discontinuation in CML is related both to low number and impaired function of NKcells. American Society of Hematology (ASH). Proceedings of the 56th ASH Annual Meeting; San Francisco, CA. Blood 2014;124(21):Abstract 812.
62. Rea D., Dulphy N., Henry G. et al. Low natural killer (NK) cell counts and functionality are associated with molecular relapse after imatinib discontinuation in patients (pts) with chronic phase (CP)-chronic myeloid leukemia (CML) with undetectable BCR-ABL transcripts for at least 2 years: preliminary results from immunostim, on behalf of STIM investigators. American Society of Hematology (ASH). Proceedings of the 55th ASH Annual Meeting. New Orleans, LA. Blood 2013;122(21):Abstract 856.
63. Mumprecht S., Schurch C., Schwaller J. et al. Programmed death 1 signaling on chronic myeloid leukemia-specific T cells results in T-cell exhaustion and disease progression. Blood 2009;114(8):1528–36. DOI: 10.1182/blood-2008-09-179697.
64. Ross D.M., Branford S. Minimal residual disease: the advantages of digital over analog polymerase chain reaction. Leuk Lymphoma 2011;52(7):1161–3. DOI: 10.3109/10428194.2011.580481.
65. Alikian M., Ellery P., Forbes M. et al. Next-generation sequencing-assisted DNA-based digital PCR for a personalized approach to the detection and quantification of residual disease in chronic myeloid leukemia patients. J Mol Diagn 2016;18(2):176–89. DOI: 10.1016/j.jmoldx.2015.09.005.
Для цитирования:
Петрова А.Н., Челышева Е.Ю., Туркина А.Г. Ремиссия без лечения у больных хроническим миелолейкозом: обзор литературы. Онкогематология. 2019;14(3):12-22. https://doi.org/10.17650/1818-8346-2019-14-3-12-22
For citation:
Petrova A.N., Chelysheva E.Yu., Turkina A.G. Treatment-free remission in patients with chronic myeloid leukemia: literature review. Oncohematology. 2019;14(3):12-22. (In Russ.) https://doi.org/10.17650/1818-8346-2019-14-3-12-22
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